Reliability assessment of the definition of ultrasound enthesitis in SpA: results of a large, multicentre, international, web-based study.

OBJECTIVES: To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA. METHODS: In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light's kappa, Cohen's kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs. RESULTS: Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light's kappa: 0.77 (0.76-0.78), 0.72 (0.71-0.73), respectively; PABAK: 0.86 (0.86-0.87), 0.73 (0.73-0.74), respectively], followed by enthesophytes/calcifications [Light's kappa: 0.65 (0.64-0.65), PABAK: 0.67 (0.67-0.68)]. This was moderate for entheseal thickening [Light's kappa: 0.41 (0.41-0.42), PABAK: 0.41 (0.40-0.42)], and fair for hypoechoic areas [Light's kappa: 0.37 (0.36-0.38); PABAK: 0.37 (0.37-0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. CONCLUSIONS: The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis.

Integrating imaging and biomarker assessment to better define psoriatic arthritis and predict response to biologic therapy.

The treatment options for PsA have substantially expanded over the last decade. Approximately 40% of patients will not respond to first-line anti-TNF-α therapies. There is limited data to help clinicians select the most appropriate biologic therapy for PsA patients, including guidance for decisions on biologic therapy switching. In this review we will examine the current understanding of predictors of response to treatment. Imaging technology has evolved to allow us to better study psoriatic disease and define disease activity, including synovitis and enthesitis. Enthesitis is implicated in the pathogenesis, diagnosis and prognosis of PsA. It appears to be a common thread among all of the various PsA clinical presentations. Enthesitis mainly manifests as tenderness, which is difficult to distinguish from FM, chronic pain and mechanically associated enthesopathy, and it might be relevant for understanding the apparent 40% failure of existing therapy. Excess adipose tissue makes if more difficult to detect joint swelling clinically, as many PsA patients have very high BMIs. Integrating imaging and clinical assessment with biomarker analysis could help to deliver stratified medicine in PsA and allow better treatment decision making. This could include which patients require ongoing biologic therapy, which class of biologic therapy that should be, and who alternatively requires management of non-inflammatory disease.

σ-Hole activation and structural changes upon perfluorination of aryl halides: direct evidence from gas phase rotational spectroscopy.

Enhancement of the σ-hole on the halogen atom of aryl halides due to perfluorination of the ring is demonstrated by use of the Extended Townes-Dailey (ETD) model coupled to a Natural Atomic Orbital Bond analysis on two perfluorinated aryl halides (C6F5Cl and C6F5Br) and their hydrogenated counterparts. The ETD analysis, which quantifies the halogen p-orbitals populations, relies on the nuclear quadrupole coupling constants which in this work are accurately determined experimentally from the rotational spectra. The rotational spectra investigated by Fourier-transform microwave spectroscopy performed in supersonic expansion are reported for the parent species of C6F5Cl and C6F5Br and their 13C, 37Cl or 81Br substituted isotopologues observed in natural abundance. The experimentally determined rotational constants combined with theoretical data at the MP2/aug-cc-pVTZ level provide precise structural information from which an elongation of the ring along its symmetry axis due to perfluorination is proved.

Resilience in Baccalaureate Nursing Students: An Exploration.

The purpose of the current study was to explore resilience in senior-level baccalaureate nursing students. Twenty-seven participants completed an online questionnaire assessing three stressors that pertained to marriage or divorce, death or loss of family members or close friends, and extreme financial hardship in the past 1 year. Resilience was measured using the 25-item Connor-Davidson Resilience Scale (CD-RISC-25) and one open-ended question about the experience of resilience. Mean CD-RISC-25 score was 73.26 (SD = 10.7; range = 45 to 96); only 33.3% of the sample was considered resilient (score >80). Qualitative data described academic stressors and support resources for resilience. Study findings underscore the relevance of resilience in nursing students. Nurse educators must help nursing students develop resilience to better prepare them for academic success and ensure a smooth transition into their professional nursing role. [Journal of Psychosocial Nursing and Mental Health Services, 56(7), 46-55.].

Sustaining Superheated Liquid within Hydrophilic Surface Texture.

During pool boiling of water, it is advantageous to keep liquid touching the surface in order to delay the onset of filmwise boiling. This allows water to remain in the nucleate boiling regime, leading to increased heat transfer. In this work, we propose a mechanism to sustain superheated liquid within hydrophilic pores. This mechanism for the design of superwetting hydrophilic surfaces does not rely on the transport of vapor and offers an additional pathway for wetting via the condensation of vapor within the surface texture. We adapt nucleation theory to design the surface geometry and implement molecular dynamics simulations to verify this concept. Simulation results are consistent with theory and demonstrate superheated liquid residing within the surface texture.

Effects of TNF-α inhibition versus secukinumab on active ultrasound-confirmed enthesitis in psoriatic arthritis.

Introduction: Enthesitis is a hallmark of psoriatic disease, but its clinical assessment is problematic in terms of diagnostic sensitivity and overlap with other comorbid conditions. Ultrasound is a useful tool that can give a more detailed assessment of enthesitis. Research demonstrates that those with persistent ultrasound entheseal disease are at risk of progressive articular damage. With limited data to guide choice between biologic therapy for psoriatic arthritis (PsA) patients, we wanted to assess the response of ultrasound-confirmed enthesitis to different forms of biologic therapies and study its utility in making more informed decisions. Methods: This was an open label observational study including patients aged ⩾18 years, who fulfil the classification criteria for PSA (CASPAR) and were due to commence on their first biologic therapy. The primary outcome was the change in MAdrid Sonographic Enthesitis Index (MASEI) score at 16 weeks of treatment. The MASEI score was also modified to assess the active elementary lesions (ActiveMASEI). Results: In all, 80 PsA patients were enrolled with 75 patients completing the study [secukinumab n = 23 and tumour necrosis factor inhibitor (TNFi) n = 52]. The mean reduction in MASEI score after 16 weeks of treatment was 3.42 with TNFi versus 1.74 with secukinumab (p = 0.097). There was a significant difference in the change in the MASEIActive score for TNFi versus secukinumab (4.37 versus 2.26; p = 0.030) and this difference was more pronounced when only power Doppler signal within 2 mm of the enthesis insertion was included (4.37 versus 2.00; p = 0.007). Clinical outcomes were similar for both classes of biologic apart from a significant reduction in regards to the Dermatology Life Quality Index and Psoriasis Area and Severity Index score with secukinumab versus TNFi. Conclusions: We have for the first time compared the effect of ultrasound-confirmed enthesitis between different forms of biologic therapies for PsA. We have seen an overall improvement in entheseal scores for both classes of medications and demonstrated a larger reduction in active entheseal disease for TNFi versus secukinumab that merits further exploration.

Introduction: An enthesis is the point at which ligament and tendon insert into the bone and enthesitis is the inflammation at these sites causing pain and reduced function.Enthesitis is particularly common in patients with psoriatic arthritis and it has been shown to be important in the development, diagnosis and prognosis of the condition. Clinical examination has limitations and imaging techniques like ultrasound have been proven to give a more detailed assessment of enthesitis potentially revealing clues to the condition itself. In psoriatic arthritis, we do not have a good way of choosing between biologic therapies that can treat inflammation. With a better understanding of enthesitis and its response to various therapies, we may be able to make better decisions. We wanted to examine the extent of enthesitis within a group of psoriatic arthritis patients who were to commence on their first biologic therapy by examining them both with ultrasound and then with clinical examination. Methods: We recruited 80 patients in which their consultant rheumatologist had decided to commence them on therapy. We carried out an ultrasound assessment of six entheseal sites as per an established assessment tool called the MAdrid Sonographic Enthesitis Index (MASEI). We then proceeded to take a history from the patients and examine all aspects of their joint disease just before they began their therapy. We repeated the ultrasound and clinical examination after 16 weeks of treatment without knowing what treatment they were on. Results: In all, 75 patients completed the study and 23 of these were treated with secukinumab, a drug that targets interleukin-17a (IL-17i), an important protein in psoriatic disease and 52 patients were treated with medications that target tumour necrosis factor inhibitor (TNFi), another important inflammatory protein. Overall, we demonstrated a reduction in ultrasound scores for entheseal disease in those treated with both classes of medication. For the TNFi group, there was a larger improvement in scores compared with the IL-17i which was not significant for the primary focus of the study, the overall MASEI score. We have also demonstrated that there may be a larger improvement in TNFi response versus IL-17i when only counting the inflammatory disease component of the MASEI score. In terms of clinical results, the findings were broadly similar except that secukinumab was better at improving skin psoriasis. Conclusion: Our work is the first with ultrasound to compare outcomes for enthesitis between classes of biologic therapy and should form the basis of future studies attempting to confirm these findings to make better decisions for those living with psoriatic arthritis.

Management of Enthesitis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Enthesitis is a key pathological and clinical feature of psoriatic arthritis (PsA) in children and adults. Enthesitis is typically assessed clinically using several validated enthesitis scoring systems that have been used in clinical trials. Enthesitis treatment response has been reported as change in the total enthesitis score or the proportion of patients who achieved complete resolution. The majority of trials in PsA did not require patients to have enthesitis at study entry since enthesitis was evaluated only as a secondary outcome. Despite the inherent limitations of the clinical assessment of enthesitis, imaging of the entheses using ultrasound or magnetic resonance imaging has rarely been used in clinical trials to assess response to treatment of enthesitis. This systematic review summarizes existing evidence regarding pharmaceutical and nonpharmaceutical interventions for enthesitis in patients with PsA to facilitate an evidence-based update of the Group for Research and Assessment in Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for PsA. METHODS: We performed a systematic literature review to identify 41 randomized clinical trials that reported enthesitis treatment response in patients with PsA. For each intervention, the response effect size was summarized and the quality of evidence was graded. Recommendations were then formulated for the various pharmacological and nonpharmacological therapies. RESULTS: We included 41 randomized clinical trials in our review and graded each intervention. CONCLUSION: Several classes of systemic conventional and advanced therapies and local measures were recommended for active enthesitis in patients with PsA.

A Multi-Matrix Metabolomic Approach in Ringed Seals and Beluga Whales to Evaluate Contaminant and Climate-Related Stressors.

As a high trophic-level species, ringed seals (Pusa hispida) and beluga whales (Delphinapterus leucas) are particularly vulnerable to elevated concentrations of biomagnifying contaminants, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and mercury (Hg). These species also face climate-change-related impacts which are leading to alterations in their diet and associated contaminant exposure. The metabolomic profile of marine mammal tissues and how it changes to environmental stressors is poorly understood. This study characterizes the profiles of 235 metabolites across plasma, liver, and inner and outer blubber in adult ringed seals and beluga whales and assesses how these profiles change as a consequence of contaminants and dietary changes. In both species, inner and outer blubber were characterized by a greater proportion of lipid classes, whereas the dominant metabolites in liver and plasma were amino acids, carbohydrates, biogenic amines and lysophosphatidylcholines. Several metabolite profiles in ringed seal plasma correlated with δ13C, while metabolite profiles in blubber were affected by hexabromobenzene in ringed seals and PBDEs and Hg in belugas. This study provides insight into inter-matrix similarities and differences across tissues and suggests that plasma and liver are more suitable for studying changes in diet, whereas liver and blubber are more suitable for studying the impacts of contaminants.

GRAPPA 2020 Research Award Recipients.

At the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, a summary of the research conducted by the recipients of the 2020 GRAPPA Research Awards was presented by the awardees. The summary of the 4 presentations is provided here.

Reliability assessment of ultrasound muscle echogenicity in patients with rheumatic diseases: Results of a multicenter international web-based study.

Objectives: To investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases. Methods: Forty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0-3) and a continuous quantitative measurement ("VAS echogenicity," 0-100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall's Tau and Pearson's Rho coefficients. Results: The semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57-0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68-0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. "VAS echogenicity" showed a high reliability both in the inter-observer [ICC = 0.80 (0.75-0.85)] and intra-observer [ICC = 0.88 (0.88-0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and "VAS echogenicity" [ICC = 0.52 (0.50-0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively). Conclusion: The results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases.

The relationship between the nail and systemic enthesitis in psoriatic arthritis.

OBJECTIVE: Psoriatic nail disease is more common in PsA than in isolated skin psoriasis (PsO). The nail is closely integrated to the DIP joint entheses. US data have shown that those patients with nail disease in PsO are more likely to have systemic enthesitis. We examined whether there was a relationship between nail disease, DIP enthesitis and systemic enthesitis in established PsA. METHODS: Forty-six PsA participants with nail disease underwent US scanning of the nail unit and the DIP entheses along with peripheral entheseal sites according to the Madrid sonographic enthesitis index (MASEI). RESULTS: At the finger level, there was a mild to moderate correlation between nail US changes and both clinical nail disease and DIP enthesis changes (DIP US) [Spearman correlation (r S) = 0.30, P < 0.001 and r S = 0.16, P < 0.001, respectively]. At the patient level, there was a moderate correlation between the nail US score and nail psoriasis severity index score and DIP US (r S = 0.33, P = 0.024 and r S = 0.43, P = 0.003, respectively). At the patient level, there was also a positive correlation between a higher nail US score and the active peripheral enthesitis score (MASEI-active) (r S = 0.35, P = 0.018). When power Doppler was part of nail US score, similar results were demonstrated at both the finger and patient levels. CONCLUSION: This study has demonstrated the utility of nail US imaging and the close relationship, on scanning, between the DIP entheses and the nail unit. In PsA, we have seen a correlation between active US changes at the nail and peripheral enthesitis, which requires further analysis. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03955861.

Characterization of C-H...π interactions in the structure of the CHClF(2)-HCCH weakly bound complex.

The microwave spectra of four isotopologues of the CHClF(2)-HCCH dimer have been measured and used to determine the structure of the complex. An initial scan over the 7-18 GHz region using the chirped-pulse microwave spectrometer at the University of Virginia provided initial assignments of the (35)Cl and (37)Cl isotopologues, with two additional H(13)C(13)CH species assigned using the resonant cavity Balle-Flygare microwave spectrometer at Eastern Illinois University. For the most abundant isotopologue, the rotational constants and quadrupole coupling constants are: A = 3301.21(4) MHz, B = 1353.4268(19) MHz, C = 1153.7351(18) MHz, χ(aa) = 34.681(12) MHz, χ(bb) = -69.70(3) MHz, χ(cc) = 35.02(2) MHz and χ(ab) = -8.8(3) MHz, in good agreement with ab initio calculations at the MP2/6-311++G(2d,2p) level. The alignment of CHClF(2) with respect to acetylene reveals a C-Hπ interaction, with a secondary C-ClH-C interaction also present between the two monomers. The fitted distance between the CHClF(2) hydrogen atom and the center of the triple bond is 2.730(6) Å, the distance between the chlorine atom and the acetylenic hydrogen is 3.061(38) Å, and the C-Hπ angle is 148.2(6)°. In addition, the centrifugal distortion constants give an estimate of the binding energy for the weak interaction of about 4.9(5) kJ mol(-1), in reasonable agreement with several similar complexes.

Macrophytes may not contribute significantly to removal of nutrients, pharmaceuticals, and antibiotic resistance in model surface constructed wetlands.

Outdoor shallow wetland mesocosms, designed to simulate surface constructed wetlands to improve lagoon wastewater treatment, were used to assess the role of macrophytes in the dissipation of wastewater nutrients, selected pharmaceuticals, and antibiotic resistance genes (ARGs). Specifically, mesocosms were established with or without populations of Typha spp. (cattails), Myriophyllum sibiricum (northern water milfoil), and Utricularia vulgaris (bladderwort). Following macrophyte establishment, mesocosms were seeded with ARG-bearing organisms from a local wastewater lagoon, and treated with a single pulse of artificial municipal wastewater with or without carbamazepine, clofibric acid, fluoxetine, and naproxen (each at 7.6µg/L), as well as sulfamethoxazole and sulfapyridine (each at 150µg/L). Rates of pharmaceutical dissipation over 28d ranged from 0.073 to 3.0d(-1), corresponding to half-lives of 0.23 to 9.4d. Based on calculated rate constants, observed dissipation rates were consistent with photodegradation driving clofibric acid, naproxen, sulfamethoxazole, and sulfapyridine removal, and with sorption also contributing to carbamazepine and fluoxetine loss. Of the seven gene determinants assayed, only two genes for both beta-lactam resistance (blaCTX and blaTEM) and sulfonamide resistance (sulI and sulII) were found in sufficient quantity for monitoring. Genes disappeared relatively rapidly from the water column, with half-lives ranging from 2.1 to 99d. In contrast, detected gene levels did not change in the sediment, with the exception of sulI, which increased after 28d in pharmaceutical-treated systems. These shallow wetland mesocosms were able to dissipate wastewater contaminants rapidly. However, no significant enhancement in removal of nutrients or pharmaceuticals was observed in mesocosms with extensive aquatic plant communities. This was likely due to three factors: first, use of naïve systems with an unchallenged capacity for nutrient assimilation and contaminant removal; second, nutrient sequestration by ubiquitous filamentous algae; and third, dominance of photolytic processes in the removal of pharmaceuticals, which overshadowed putative plant-related processes.

Analysis of PEG 400 in perfusate samples by aqueous normal phase (ANP) chromatography with evaporative light scattering detection.

A rapid method for the analysis of polyethylene glycol (PEG 400) in perfusate samples is presented. Because PEG 400 lacks a strong chromophore in the UV range, detection was accomplished using evaporative light scattering detection (ELSD). In order to optimize the ELSD signal performance for a volatile mobile phase, the chromatographic separation was optimized using aqueous normal phase conditions on a Cogent® Diamond Hydride column.