Can numerical rating scales of disease impact be used as targets for patient-centred management in rheumatoid arthritis?

OBJECTIVES: Patient centred care is an increasingly important paradigm. Applying a treat-to-target strategy to the impact of the disease in patients' lives seems a very promising tool to serve this purpose. We aimed to evaluate if maximum acceptable impact scores (target-values) defined at the population level provide an appropriate representation for most individual patients. To determine if the individually established target values of impact are consistent enough to be used in a treat-to-target strategy. METHODS: Consecutive patients with rheumatoid arthritis were asked to indicate, in two consecutive visits, the maximum severity of impact they considered acceptable to live with for the rest of their lives, in the seven domains of Rheumatoid Arthritis Impact of Disease score. The individual adequacy of population-based reference values was assessed by measures of dispersion. Stability of individual target-values were evaluated through intraclass correlation coefficient. Socio-demographic, clinical and psychological features were tested as co-factors of stability. RESULTS: 299 patients were included. The dispersion of targets was wide (CV>0.68), thus limiting the use of any population-based single values as targets for the individual patients. Although the mean target values were very similar in both visits for all domains, reliability was poor in all cases (ICCs: 0.37-0.47). Only 25-30% of the patients selected the same target value in the 2 visits. No explanatory factors for (non-)stability were identified. CONCLUSIONS: Quantified impact targets defined at population level are not appropriate for individual patient care. Research on alternative tools to support patient-centred, target-oriented management strategies is warranted.

The Role of Lung Ultrasound in Systemic Sclerosis: A Systematic Review.

BACKGROUND: In systemic sclerosis (SSc), high-resolution computed tomography (HRCT) of the chest is the standard criterion for the diagnosis of interstitial lung disease (ILD). However, recent evidence suggests that lung ultrasound (LUS) can also detect ILD, without radiation exposure. Thus, our goal was to perform a systematic review, aiming to clarify the role of LUS in the detection of ILD in SSc. METHODS: A systematic review was carried out in PubMed and EMBASE (PROSPERO register number CRD42022293132), to identify studies that compared LUS with HRCT in the detection of ILD in patients with SSc. Risk of bias was assessed with the QUADAS-2 () tool. RESULTS: Three hundred seventy-five publications were identified. After screening, 13 were included in the final analysis. No study presented high risk of bias. Lung ultrasound protocol was highly heterogeneous between authors, specifically concerning transducer, intercostal spaces evaluated, exclusion criteria, and definition of positive LUS. Most authors evaluated the presence of B-lines as a surrogate of ILD, with only 4 focusing on pleural changes. A positive correlation between LUS findings and ILD detected by HRCT was reported. Results also revealed high sensitivity (74.3%-100%) but variable specificity (16%-99%). Positive predictive value varied between 16% and 95.1%, and negative predictive value between 51.7% and 100%. CONCLUSION: Lung ultrasound is sensitive in the detection of ILD, but specificity must be optimized. The value of pleural evaluation also requires further investigation. Moreover, a consensus is needed to define a uniform LUS protocol to implement in future investigations.

The Rab11-regulated endocytic pathway and BDNF/TrkB signaling: Roles in plasticity changes and neurodegenerative diseases.

Neurons are highly polarized cells that rely on the intracellular transport of organelles. This process is regulated by molecular motors such as dynein and kinesins and the Rab family of monomeric GTPases that together help move cargo along microtubules in dendrites, somas, and axons. Rab5-Rab11 GTPases regulate receptor trafficking along early-recycling endosomes, which is a process that determines the intracellular signaling output of different signaling pathways, including those triggered by BDNF binding to its tyrosine kinase receptor TrkB. BDNF is a well-recognized neurotrophic factor that regulates experience-dependent plasticity in different circuits in the brain. The internalization of the BDNF/TrkB complex results in signaling endosomes that allow local signaling in dendrites and presynaptic terminals, nuclear signaling in somas and dynein-mediated long-distance signaling from axons to cell bodies. In this review, we briefly discuss the organization of the endocytic pathway and how Rab11-recycling endosomes interact with other endomembrane systems. We further expand upon the roles of the Rab11-recycling pathway in neuronal plasticity. Then, we discuss the BDNF/TrkB signaling pathways and their functional relationships with the postendocytic trafficking of BDNF, including axonal transport, emphasizing the role of BDNF signaling endosomes, particularly Rab5-Rab11 endosomes, in neuronal plasticity. Finally, we discuss the evidence indicating that the dysfunction of the early-recycling pathway impairs BDNF signaling, contributing to several neurodegenerative diseases.

Predictors of Mortality and Refracture in Patients Older Than 65 Years With a Proximal Femur Fracture.

OBJECTIVES: To evaluate potential predictors of subsequent fracture and increased mortality in a population 65 years or older who suffered a proximal femur fragility fracture. METHODS: This was a longitudinal study that included patients with a proximal femur fragility fracture, referred from the Orthopedics Inpatient Department to the Rheumatology Department's Fracture Liaison Service, from March 2015 to March 2017. RESULTS: Five hundred twenty-two patients were included, with a median age (IQR) of 84 years (interquartile range [IQR], 11 years), 79.7% (n = 416) female. Nine percent (n = 47) suffered a new fracture, with a median time to event of 298 days (IQR, 331 days). Cumulative probability without refracture at 12 months was 93% (95% confidence interval [CI], 90.2%-95.0%); 22.8% (n = 119) patients died, with median time to death of 126 days (IQR, 336 days). Cumulative survival probability at 12 months was 81.7 (95% CI, 77.9-84.8). Neurologic disease (hazard ratio [HR], 2.30; 95% CI, 0.97-5.50; p = 0.06) and chronic obstructive pulmonary disease (HR, 3.61; 95% CI, 1.20-10.9; p = 0.022) were both predictors of refracture. Age older than 80 years (HR, 1.54; 95% CI, 0.99-2.38; p = 0.052), higher degree of dependence (HR, 1.24;95% CI, 1.09-1.42; p = 0.001), male sex (HR, 1.55; 95% CI, 1.03-2.33; p = 0.034), femoral neck fracture (HR, 0.45; 95% CI, 0.24-0.88; p = 0.018), Charlson score (HR, 2.08; 95% CI, 1.17-3.69; p = 0.012), heart failure (HR, 2.44; 95% CI, 1.06-5.63; p = 0.037), hip bone mass density (HR, 3.99; 95% CI, 1.19-13.4; p = 0.025), hip T score (HR, 0.64; 95% CI, 0.44-0.93; p = 0.021), and ß-crosslaps (HR, 1.98; 95% CI, 1.02-3.84; p = 0.042) all predicted a higher mortality. CONCLUSIONS: Neurologic disease and chronic obstructive pulmonary disease may increase the risk of subsequent fracture after a hip fracture. Male sex, age, autonomy degree, femur bone mass density/T score, fracture type, Charlson score, diabetes mellitus, heart failure, and ß-crosslaps had significant impact on survival. The authors highlight ß-crosslaps as a potential serological marker of increased mortality in clinical practice.

Plastid genome evolution in Amazonian açaí palm (Euterpe oleracea Mart.) and Atlantic forest açaí palm (Euterpe edulis Mart.).

KEY MESSAGE: The plastomes of E. edulis and E. oleracea revealed several molecular markers useful for genetic studies in natural populations and indicate specific evolutionary features determined by vicariant speciation. Arecaceae is a large and diverse family occurring in tropical and subtropical ecosystems worldwide. E. oleracea is a hyperdominant species of the Amazon forest, while E. edulis is a keystone species of the Atlantic forest. It has reported that E. edulis arose from vicariant speciation after the emergence of the belt barrier of dry environment (Cerrado and Caatinga biomes) between Amazon and Atlantic forests, isolating the E. edulis in the Atlantic forest. We sequenced the complete plastomes of E. edulis and E. oleracea and compared them concerning plastome structure, SSRs, tandem repeats, SNPs, indels, hotspots of nucleotide polymorphism, codon Ka/Ks ratios and RNA editing sites aiming to investigate evolutionary traits possibly affected by distinct environments. Our analyses revealed 303 SNPs, 91 indels, and 82 polymorphic SSRs among both species. Curiously, the narrow correlation among localization of repetitive sequences and indels strongly suggests that replication slippage is involved in plastid DNA mutations in Euterpe. Moreover, most non-synonymous substitutions represent amino acid variants in E. edulis that evolved specifically or in a convergent manner across the palm phylogeny. Amino acid variants observed in several plastid proteins in E. edulis were also identified as positive signatures across palm phylogeny. The higher incidence of specific amino acid changes in plastid genes of E. edulis in comparison with E. oleracea probably configures adaptive genetic variations determined by vicariant speciation. Our data indicate that the environment generates a selective pressure on the plastome making it more adapted to specific conditions.

Happiness, quality of life and their determinants among people with systemic sclerosis: a structural equation modelling approach.

BACKGROUND: Patients' objectives and experiences must be core to the study and management of chronic diseases, such as SSc. Although patient-reported outcomes are attracting increasing attention, evaluation of the impact of disease on the overall subjective well-being, equivalent to 'happiness', is remarkably lacking. OBJECTIVES: To examine the determinants of happiness and quality of life in patients with SSc, with emphasis on disease features and personality traits. METHODS: Observational, cross-sectional multicentre study, including 142 patients, with complete data regarding disease activity, disease impact, personality, health-related quality of life (HR-QoL) and happiness. Structural equation modelling was used to evaluate the association between the variables. RESULTS: The results indicated an acceptable fit of the model to the data. Perceived disease impact had a significant negative direct relation with HR-QoL (ß = -0.79, P < 0.001) and with happiness (ß = -0.52, P < 0.001). Positive personality traits had a positive relation with happiness (ß = 0.36, P = 0.002) and an important indirect association upon QoL (ß = 0.43) and happiness (ß = 0.23). Perceived disease impact is influenced by body image, fatigue and SSc-related disability to a higher degree (ß = 0.6-0.7) than by disease activity (ß = 0.28) or form (ß = 0.17). Impact of disease had a much stronger relation with HR-QoL than with happiness. CONCLUSIONS: The results suggest that treatment strategies targeting not only disease control but also the mitigation of relevant domains of disease impact (body image, fatigue, global disability) may be important to improve patients' experience of the disease. The reinforcement of resilience factors, such as positive psychological traits, may also play a contributory role towards better patient outcomes.

Serendipita restingae sp. nov. (Sebacinales): an orchid mycorrhizal agaricomycete with wide host range.

The Serendipitaceae family was erected in 2016 to accommodate the Sebacinales 'group B' clade, which contains peculiar species of cultivable root-associated fungi involved in symbiotic associations with a wide range of plant species. Here we report the isolation of a new Serendipita species which was obtained from protocorms of the terrestrial orchid Epidendrum fulgens cultivated in a greenhouse. This species is described based on phylogenetic analysis and on its microscopic and ultrastructural features in pure culture and in association with the host's protocorms. Its genome size was estimated using flow cytometry, and its capacity to promote the germination of E. fulgens seeds and to associate with roots of Arabidopsis thaliana was also investigated. Serendipita restingae sp. nov. is closely related to Serendipita sp. MAFF305841, isolated from Microtis rara (Orchidaceae), from which it differs by 14.2% in the ITS region and by 6.5% in the LSU region. It produces microsclerotia formed of non-monilioid hyphae, a feature that was not reported for the Sebacinales hitherto. Serendipita restingae promoted the germination of E. fulgens seeds, forming typical mycorrhizal pelotons within protocorm cells. It was also able to colonize the roots of Arabidopsis thaliana under in vitro conditions. Arabidopsis plants grown in association with S. restingae increased their biomass more than fourfold. Serendipita restingae is the first Serendipitaceae species described for the Americas.

Interventional pain training using phantom model during COVID-19 pandemic.

BACKGROUND: Fluoroscopic-guided lumbar procedures have increased in daily pain practice because the lumbar spine is one of the most common sources of pain. Interventional pain fellows must develop a minimum number of skills during their training in order to achieve the competences without neglecting radiological safety. However, medical training in fluoroscopic-guided interventions is being affected by the current coronavirus disease 2019 (COVID-19) situation. METHODS: The objective of this study was to evaluate the use of a phantom model for lumbar injection as a training strategy during the COVID-19 pandemic in fellows of interventional pain. The study was divided into theoretical and practical modules. The hands-on practice was performed in a lumbar model phantom where fellows were evaluated in four fluoroscopically guided approaches: intra-articular facet block (IAFB), medial branch block (MBB), transforaminal block (TFB), and interlaminar block (ILB) divided in 5 sessions. The aim was to make as many punctures as possible in every session. We measured total procedural performance (TPP), total needle hand time (TNH), and total radiation dose generated by the fluoroscopic machine (TRD) during each procedure. Additionally, a survey was applied to evaluate confidence and satisfaction before and after training. RESULTS: A total of 320 lumbar punctures were completed. The results were statistically significant in all approaches attempted (p < 0.01). The fellow's survey for satisfaction and confidence demonstrated a significant difference between pre and post-test (p < 0.01). CONCLUSIONS: The results of this study highlight the importance of adaptations and adoption of new educational models. The use of the phantom model for simulation could be a strategy for other emerging situations, like the COVID-19 pandemic. Including this practice in the interventional pain programs could lead to better results for the patient and operator radiology safety.

Characterization of the complete plastid genome of Butia eriospatha (Arecaceae).

Butia eriospatha is an endemic palm species from the Atlantic Rainforest in Brazil, a biodiversity hotspot. This species is currently listed in the IUCN red list as vulnerable and lacks specific plastid markers for population genetics studies. In addition, the evolutionary relationship within the genus Butia is not yet well resolved. Here, we sequenced and characterized the complete plastid genome (plastome) sequence of B. eriospatha. The complete plastome sequence is 154,048 bp in length, with the typical quadripartite structure. This plastome length and genes content is consistent with other six species from tribe Cocoseae. However, the Inverted Repeat (IR) borders show some variation among the analyzed species from this tribe. Species from the Bactridinae (Astrocaryum and Acrocomia) and Elaeidinae (Elaeis) subtribes present the rps19 gene completely duplicated in the IR region. In contrast, all plastomes sequenced from the subtribe Attaleinae (Butia, Cocos, Syagrus) present one complete CDS of rps19 and one partial copy of rps19. The difference in the IR/LSC junctions between Attaleinae and the sister clades Bactridinae + Elaeidinae might be considered an evolutionary signal and the plastome sequence of B. eriopatha may be used in future studies of population genetics and phylogeny.

Molecular relationships of Campomanesia xanthocarpa within Myrtaceae based on the complete plastome sequence and on the plastid ycf2 gene.

Plastomes are very informative structures for comparative phylogenetic and evolutionary analyses. We sequenced and analyzed the complete plastome of Campomanesia xanthocarpa and compared its gene order, structure, and evolutionary characteristics within Myrtaceae. Analyzing 48 species of Myrtaceae, we identified six genes representing 'hotspots' of variability within the plastomes (ycf2, atpA, rpoC2, pcbE, ndhH and rps16), and performed phylogenetic analyses based on: (i) the ycf2 gene, (ii) all the six genes identified as 'hotspots' of variability, and (iii) the genes identified as 'hotspots' of variability, except the ycf2 gene. The structure, gene order, and gene content of the C. xanthocarpa plastome are similar to other Myrtaceae species. Phylogenetic analyses revealed the ycf2 gene as a promissing region for barcoding within this family, having also a robust phylogenetic signal. The synonymous and nonsynonymous substitution rates and the Ka/Ks ratio revealed low values for the ycf2 gene among C. xanthocarpa and the other 47 analyzed species of Myrtaceae, with moderate purifying selection acting on this gene. The average nucleotide identity (ANI) analysis of the whole plastomes produced phylogenetic trees supporting the monophyly of three Myrtaceae tribes. The findings of this study provide support for planning conservation, breeding, and biotechnological programs for this species.