The study of galactomannans with different molecular weights and their ability to form microparticles suitable for pulmonary delivery.

The influence of locust bean gum (LBG) galactomannans (GMs) molecular weight (Mw) to assemble microparticulate systems was evaluated, and carriers for deep lung delivery were developed. A commercial batch of LBG with a mannose/galactose (M/G) ratio of 2.4 (batch 1) was used to study the influence of different microwave partial acid hydrolysis conditions on carbohydrate composition, glycosidic linkages, and aqueous solutions viscosity. The microwave treatment did not affect the composition, presenting 4-Man (36-42 %), 4,6-Man (27-35 %), and T-Gal (24-25 %) as the main glycosidic linkages. Depolymerization led to a viscosity reduction (≤0.005 Pa·s) with no major impact on polysaccharide debranching. The structural composition of the LBG galactomannans were further elucidated with sequence-specific proteins using carbohydrate microarray technologies. A second batch of LBG (M/G 3.3) was used to study the impact of GMs with different Mw on microparticle assembling, characteristics, and insulin release kinetics. The low-Mw GMs microparticles led to a faster release (20 min) than the higher-Mw (40 min) ones, impacting the release kinetics. All microparticles exhibited a safety profile to cells of the respiratory tract. However, only the higher-Mw GMs allowed the assembly of microparticles with sizes suitable for this type of administration.

Effects of vitamin D3, omega-3 s and a simple strength training exercise program on bone health: the DO-HEALTH randomized controlled trial.

INTRODUCTION: Evidence on the effects of Vitamin D, omega-3 s and exercise on aBMD in healthy older adults is limited. We examined whether vitamin D3, omega-3 s, or a simple home-based exercise program (SHEP), alone or in combination, over three years, improve lumbar spine (LS), femoral neck (FN) or total hip (TH) aBMD assessed by DXA. METHODS: aBMD was a secondary outcome in DO-HEALTH, a 3-year, multicenter, double-blind, randomized 2 × 2 × 2 factorial design trial in generally healthy older adults age ≥ 70 years. The study interventions were vitamin D3 (2000IU/d), omega-3 s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination in 8 treatment arms. Mixed effect models were used adjusting for age, sex, BMI, prior fall, study site and baseline level of the outcome. Main effects were assessed in the absence of an interaction between the interventions. Subgroup analyses by sex, physical activity level, dietary calcium intake, serum 25(OH)D levels, and fracture history were conducted. RESULTS: DXA scans were available for 1493 participants (mean age 75 years; 80.4% were physically active, 44% had 25(OH)D levels <20 ng/ml). At the LS and FN sites, none of the treatments showed a benefit. At the TH, vitamin D vs. no vitamin D treatment showed a significant benefit across 3 years (difference in adjusted means [AM]: 0.0035 [95% CI 0.0011, 0.0059] g/cm2). Furthermore, there was a benefit for vitamin D vs. no vitamin D treatment on LS aBMD in the male subgroup of (interaction P = 0.003; ∆AM: 0.0070 [95% CI 0.0007, 0.0132] g/cm2). CONCLUSIONS: Omega-3 and SHEP had no benefit on aBMD in healthy, active and largely vitamin D replete older adults. Our study suggests a small benefit of 2000 IU vitamin D daily on TH aBMD overall and LS aBMD among men, however, effect sizes were very modest and the clinical impact of these findings is unclear.

Vitamin D, omega-3 fatty acids (omega-3 s) and strength training are simple but promising strategies to improve bone health, however, their effect in healthy older adults over a period of three years was unclear. In this study, we examined whether daily vitamin D supplementation (2000 IU/d), daily omega-3 s supplementation (1 g/d) or a simple strength training program performed three times per week, either applied alone (e.g., only vitamin D supplements) or in combination (e.g., vitamin D and omega-3 s supplements) could improve bone density at the spine, hip or femoral neck. We included 1493 healthy older adults from Switzerland, Germany, France and Portugal who were at least 70 years of age and who had not experienced any major health events in the five years before study start. Taking omega-3 s supplements showed no benefit for bone density. Similarly, the simple strength exercise program showed no benefit. In contrast, participants receiving daily vitamin D supplements experienced a benefit at the hip. However, it should be noted that the effect across three years was very small.

Effects of vitamin D, omega-3 and a simple strength exercise programme in cardiovascular disease prevention: The DO-HEALTH randomized controlled trial.

BACKGROUND: The effects of non-pharmaceutical interventions in the prevention of cardiovascular diseases (CVD) in older adults remains unclear. Therefore, the aim was to investigate the effect of 2000 IU/day of vitamin D3, omega-3 fatty acids (1 g/day), and a simple home strength exercise program (SHEP) (3×/week) on lipid and CVD biomarkers plasma changes over 3 years, incident hypertension and major cardiovascular events (MACE). METHODS: The risk of MACE (coronary heart event or intervention, heart failure, stroke) was an exploratory endpoint of DO-HEALTH, incident hypertension and change in biomarkers were secondary endpoints. DO-HEALTH is a completed multicentre, randomised, placebo-controlled, 2 × 2 × 2 factorial design trial enrolling 2157 Europeans aged ≥70 years. RESULTS: Participants' median age was 74 [72, 77] years, 61.7% were women, 82.5% were at least moderately physically active, and 40.7% had 25(OH)D < 20 ng/mL at baseline. Compared to their controls, omega-3 increased HDL-cholesterol (difference in change over 3 years: 0.08 mmol/L, 95% CI 0.05-0.10), decreased triglycerides (-0.08 mmol/L, (95%CI -0.12 to -0.03), but increased total- (0.15 mmol/L, 95%CI 0.09; 0.2), LDL- (0.11 mmol/L, 0.06; 0.16), and non-HDL-cholesterol (0.07 mmol/L, 95%CI 0.02; 0.12). However, neither omega-3 (adjustedHR 1.00, 95%CI 0.64-1.56), nor vitamin D3 (aHR 1.37, 95%CI 0.88-2.14), nor SHEP (aHR 1.18, 95%CI 0.76-1.84) reduced risk of MACE or incident hypertension compared to control. CONCLUSION: Among generally healthy, active, and largely vitamin D replete, older adults, treatment with omega-3, vitamin D3, and/or SHEP had no benefit on MACE prevention. Only omega-3 supplementation changed lipid biomarkers, but with mixed effects. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT01745263.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

The SLE-DAS provides an accurate and feasible flare tool in the clinical setting: a validation study.

OBJECTIVE: To assess the criterion validity of the SLE disease activity score (SLE-DAS) flare tool and compare its performance in identifying flares against other instruments. METHODS: Patients with SLE fulfilling SLE-DAS low disease activity at baseline were included from two academic lupus clinics. During follow-up, flares were identified by the senior attending clinician, applying the expert-consensus-based definition as gold-standard. The first clinical flare from flaring patients, and the first visit after baseline in patients without flares were analysed. In each no flare/flare visits, we assessed flares by SLE-DAS (score increase ≥1.72), classic-SELENA Flare Index (c-SELENA FI), revised-SELENA FI (r-SELENA FI), and SLEDAI-2K (score increase ≥4). We estimated the sensitivity, specificity, and Cohen's Kappa agreement of each flare tool against the gold-standard. RESULTS: A total of 442 patients were included and followed-up for 22.9 (14.2) months. Incidence of flares was 8.19/100 patient-years, with 69 patients experiencing flares. The SLE-DAS identified 96.6% of the expert-defined flares implying a treatment change and classified 28.0% of those as moderate/severe. Sensitivity and specificity for the gold-standard flare definition were: SLE-DAS 97.1% and 97.3%, c-SELENA FI 88.4% and 98.1%, r-SELENA FI 88.4% and 96.8%, SLEDAI-2K 56.5% and 99.2%, respectively. Kappa coefficients of these instruments were 0.902 (95% CI: 0.847, 0.957), 0.870 (95% CI: 0.805, 0.935), 0.832 (95% CI: 0.761, 0.903), and 0.663 (95% CI: 0.557, 0.769), respectively. The number of flare misclassifications was lowest with the SLE-DAS, and highest with the SLEDAI-2K. CONCLUSION: The SLE-DAS accurately identifies and categorizes flares as mild or moderate/severe. It is feasible and, thus, may help the physicians' treatment decisions in the clinical practice setting.

Capillary electrophoresis with capacitively coupled contactless conductivity detection (C4 D) for rapid and simple determination of lactate in sweat.

An analytical method based on capillary electrophoresis (CE) using capacitively coupled contactless conductivity detection (C4 D) was developed and validated for fast, straightforward, and reliable determination of lactate in artificial and human sweat samples. The background electrolyte was composed of equimolar concentrations (10 mmol/L) of 2-(N-morpholino)ethanesulfonic acid and histidine, with 0.2 mmol/L of cetyltrimethylammonium bromide as electroosmotic flow inverter. The limit of detection and quantification were 3.1 and 10.3 µmol/L, respectively. Recoveries in the 97 to 118% range were obtained using sweat samples spiked with lactate at three concentration levels, indicating an acceptable accuracy. The intraday and interday precisions were 1.49 and 7.08%, respectively. The proposed CE-C4 D method can be a starting point for monitoring lactate concentrations in sweat samples for diagnostics, physiological studies, and sports performance assessment applications.

A taxonomy of threat and soothing influences in rheumatic and musculoskeletal diseases and central sensitivity syndromes.

Background: An imbalance in affect regulation, reflected by a hyperactive threat system and hypoactive soothing system, may impact physical symptoms in people with rheumatic and musculoskeletal diseases (RMD) and central sensitivity syndromes (CSS), including chronic fatigue syndrome, fibromyalgia, and irritable bowel syndrome. This study aimed to identify and structure comprehensive overviews of threat and soothing influences that may worsen or alleviate physical symptoms in people with RMD or CSS. Method: A concept mapping procedure was used. An online open-question survey (N = 686, 641 [93.4%] women) yielded comprehensive sets of 40 threats and 40 soothers that were individually sorted by people with RMD or CSS (N = 115, 112 [97.4%] women). Results: Hierarchical cluster analyses generated eight threat clusters: environmental stimuli, physical symptoms, food and drugs, inactivity, demands, effort, invalidation, and emotional stress. Ten soother clusters were identified: social emotional support, rest and balance, pleasant surroundings, illness understanding, positive mindset and autonomy, spirituality, leisure activity, wellness, treatment and care, and nutrition and treats. Conclusions: Our study provided a comprehensive taxonomy of threats and soothers in people with RMD or CSS. The results can be used in experimental research to label threat and soothing stimuli and in clinical practice to screen and monitor relevant treatment targets.

Effect of DMPEI coating against biofilm formation on PVC catheter surface.

Urinary tract infections (UTIs) are a significant cause of morbidity in healthcare systems and are prominently associated with applying urethral catheters, particularly in surgeries. Polyvinyl chloride (PVC) is extensively utilized in the fabrication of catheters. Biofilms, complex polymeric constructions, provide a protective milieu for cell multiplication and the enhancement of antibiotic resistance. Strategies to counteract biofilm development on medical apparatuses' surfaces incorporate antimicrobial agents such as N,N-dodecyl, and methyl polyethylenimine (DMPEI). This research endeavored to characterize the morphology of PVC and PVC-DMPEI surfaces utilizing Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) and to gauge hydrophobicity through contact angle measurements. Employing Escherichia coli, Staphylococcus aureus, and Candida albicans in adhesion assays enabled the assessment of DMPEI's efficacy in preventing microbial adherence to PVC. Butanol successfully solubilized 2 mg.mL-1 DMPEI without altering the PVC structure. SEM results substantiated the formation of a DMPEI layer on the PVC surface, which led to decreased surface roughness, as validated by AFM, and increased hydrophilicity, as demonstrated by contact angle evaluations. E. coli, S. aureus, and C. albicans exhibited significant adhesion reduction, 89.3%, 94.3%, and 86.6% on PVC-DMPEI surfaces. SEM visualizations confirmed reduced cellular colonization on PVC-DMPEI and highlighted considerable morphological modifications in E. coli. Consequently, DMPEI films effectively minimize the adhesion of E. coli, S. aureus, and C. albicans on PVC surfaces. DMPEI, with its potential as a protective coating for innovative medical devices, promises to inhibit biofilm adherence effectively.

MITIG.RA: study protocol of a tailored psychological intervention for managing fatigue in rheumatoid arthritis randomized controlled trial.

BACKGROUND: Despite remarkable medical advances in the treatment of rheumatoid arthritis (RA), a subset of patients fails to achieve complete clinical remission, as the Patient Global Assessment (PGA) of disease activity remains above 1, even after the inflammatory process is brought under control. This so-called state of 'PGA-near-remission' negatively impacts individuals' functioning and potentiates inadequate care. Fatigue is a distressing and disabling symptom frequently reported by patients in PGA-near-remission, and its management remains challenging. While classic cognitive-behavioural interventions show some benefits in managing fatigue, there is potential for improvement. Recently, contextual-cognitive behavioural therapies (CCBT), like mindfulness, acceptance, and compassion-based interventions, have shown promising results in fatigue-associated disorders and their determinants. This study primarily aims to examine the efficacy of the Compassion and Mindfulness Intervention for RA (MITIG.RA), a novel intervention combining different components of CCBT, compared to treatment-as-usual (TAU) in the management of RA-associated fatigue. Secondary aims involve exploring whether MITIG.RA produces changes in the perceived impact of disease, satisfaction with disease status, levels of depression, and emotion-regulation skills. METHODS: This is a single center, two-arm parallel randomized controlled trial. Patients will be screened for eligibility and willingness to participate and will be assessed and randomized to the experimental (MITIG.RA + TAU) or control condition (TAU) using computer randomization. MITIG.RA will be delivered by a certified psychologist and comprises eight sessions of 2 h, followed by two booster sessions. Outcomes will be assessed through validated self-report measures, including fatigue (primary outcome), perceived impact of disease, depressive symptoms, mindfulness, self-compassion, safety, and satisfaction (secondary outcomes). Assessment will take place at baseline, post-intervention, before the first and second booster sessions (weeks 12 and 20, respectively), and at 32 and 44 weeks after the interventions' beginning. DISCUSSION: We expect MITIG.RA to be effective in reducing levels of RA-associated fatigue. Secondarily, we hypothesize that the experimental group will show improvements in the overall perceived impact of disease, emotional distress, and emotion regulation skills. Our findings will contribute to determine the benefits of combining CCBT approaches for managing fatigue and associated distress in RA. TRIAL REGISTRATION: ClinicalTrials.gov NCT05389189. Registered on May 25, 2022.

High Pressure and Pasteurization Effects on Dairy Cream.

Dairy cream, a common ingredient in various dishes and food products, is susceptible to rapid microbial growth due to its high water activity (≈0.97) and pH (≈6.7). Thus, it requires proper processing conditions to ensure food safety and extend shelf life. High-pressure processing (HPP) has emerged as a nonthermal food pasteurization method, offering an alternative to conventional heat-based techniques to obtain tastier, fresh-like, and safe dairy products without undesirable heat-induced alterations. This study assessed the impact of HPP (450 and 600 MPa for 5 and 15 min at 7 °C) and thermal pasteurization (75 °C for 15 s) on the microbiological and physicochemical attributes of dairy cream immediately after processing and throughout refrigerated storage (4 °C). HPP-treated samples remained microbiologically acceptable even on the 51st day of storage, unlike thermally pasteurized samples. Moreover, HPP decreased inoculated Escherichia coli and Listeria innocua counts by more than 6 log units to undetectable levels (1.00 log CFU/mL). pH, color (maximum variation of ΔE* up to 8.43), and fatty acid profiles remained relatively stable under varying processing conditions and during storage. However, viscosity exhibited higher values for HPP-treated samples (0.028 ± 0.003 Pa·s) compared to thermally processed ones (0.016 ± 0.002 Pa·s) by the 28th day of storage. Furthermore, volatile compounds (VOCs) of all treated samples presented a tendency to increase throughout storage, particularly acids and aliphatic hydrocarbons. These findings show HPP's potential to significantly extend the shelf life of highly perishable dairy cream by at least 15 days compared to thermal pasteurization.

Effects of Sequential Combination of Moderate Pressure and Ultrasound on Subsequent Thermal Pasteurization of Liquid Whole Egg.

As an alternative to commercial whole egg thermal pasteurization (TP), the sequential combination of moderate pressure (MP) and/or ultrasound (US) pre-treatments prior to a shorter TP was evaluated. The use of US alone or in combination with MP or TP resulted in an inactivation that was far from that of commercial TP. Nevertheless, when these three technologies were combined (MP-US-TP, 160 MPa/5 min-50% amplitude/1 min-60 °C/1.75 min), a safety level comparable to that of commercial TP was established. This was likely due to a decrease in the thermal resistance of Salmonella Senftenberg 775/W caused by MP and US pre-treatments. Regarding liquid whole egg (LWE) properties, using raw LWE as a reference, TP and MP treatments each decreased protein solubility (7-12%), which was accompanied by a viscosity increment (41-59%), whereas the US-only and MP-US-TP treatments improved protein solubility (about 4%) and reduced viscosity (about 34%). On average, all treatments lowered the emulsifying properties of LWE by 35-63%, with the MP-US-TP treatment having a more dramatic impact than commercial TP. In addition, the US-only, MP-only, and MP-US-TP treatments had the greatest impact on the volatile profile of LWE, lowering the concentration of the total volatile components. In comparison to commercial TP, LWE treated with MP-US-TP exhibited greater protein solubility (19%), lower viscosity (56%), and comparable emulsifying stability, but with a decreased emulsifying capacity (39%) and a lower total volatile compounds content (77%). Considering that a combined treatment (MP-US-TP) is lethally equivalent to commercial TP, but the latter better retained the quality properties of raw LWE, including volatiles, the application of MP followed by US pre-treatments before a shorter TP did not demonstrate significant advantages on quality parameters in comparison to commercial TP.

Comparing Different Packaging Conditions on Quality Stability of High-Pressure Treated Serra da Estrela Cheeses during Cold Storage.

Serra da Estrela cheese with a Protected Designation of Origin (PDO) is a traditional cheese that is wrapped in paper without vacuum. High-pressure processing (HPP), which requires vacuum packaging of the cheese, has been used for its cold pasteurization to overcome safety issues. In this study, two packaging systems were studied: non-vacuum greaseproof paper wrapping package and vacuum packaging in plastic film. Lactococci, lactobacilli, enterococci, and total mesophiles reached ca. 8 log cfu g-1 and 4-6 log cfu g-1 in control (unpasteurized) and HPP-treated cheeses, respectively, with no significant differences between packaging systems. Spoilage microorganisms' viable cell numbers were reduced to <3 log cfu g-1 (quantification limit) in HPP-treated cheeses, independently of the packaging system. Yeasts and molds reached >5 log cfu g-1 in non-vacuum paper-wrapped cheeses. A vacuum-packaging system enabled better control of cheese proteolysis, which was revealed to be closer to that of the original control cheese values at the end of the 10-month storage period. In addition, cheese stored under vacuum film packaging became harder than non-vacuum paper-wrapped cheeses at each time point. Overall, conventional non-vacuum paper wrapping is adequate for short storage periods (<3 months), but for long periods vacuum packaging in plastic film is preferable.

Umbilical-Cord-Derived Mesenchymal Stromal Cells Modulate 26 Out of 41 T Cell Subsets from Systemic Sclerosis Patients.

Systemic sclerosis (SSc) is an immune-mediated disease wherein T cells are particularly implicated, presenting a poor prognosis and limited therapeutic options. Thus, mesenchymal-stem/stromal-cell (MSC)-based therapies can be of great benefit to SSc patients given their immunomodulatory, anti-fibrotic, and pro-angiogenic potential, which is associated with low toxicity. In this study, peripheral blood mononuclear cells from healthy individuals (HC, n = 6) and SSc patients (n = 9) were co-cultured with MSCs in order to assess how MSCs affected the activation and polarization of 58 different T cell subsets, including Th1, Th17, and Treg. It was found that MSCs downregulated the activation of 26 out of the 41 T cell subsets identified within CD4+, CD8+, CD4+CD8+, CD4-CD8-, and γδ T cells in SSc patients (HC: 29/42) and affected the polarization of 13 out of 58 T cell subsets in SSc patients (HC: 22/64). Interestingly, SSc patients displayed some T cell subsets with an increased activation status and MSCs were able to downregulate all of them. This study provides a wide-ranging perspective of how MSCs affect T cells, including minor subsets. The ability to inhibit the activation and modulate the polarization of several T cell subsets, including those implicated in SSc's pathogenesis, further supports the potential of MSC-based therapies to regulate T cells in a disease whose onset/development may be due to immune system's malfunction.

Points to consider: EULAR-UEMS standards for the training of European rheumatologists.

BACKGROUND: Postgraduate rheumatology training programmes are already established at a national level in most European countries. However, previous work has highlighted a substantial level of heterogeneity in the organisation and, in part, content of programmes. OBJECTIVE: To define competences and standards of knowledge, skills and professional behaviours required for the training of rheumatologists. METHODS: A European Alliance of Associations for Rheumatology (EULAR) task force (TF) of 23 experts, including two members of the European Union of Medical Specialists (UEMS) section of rheumatology, was convened. The mapping phase consisted of the retrieval of key documents on specialty training in rheumatology and other related specialties across a broad set of international sources. The content of these documents was extracted and represented the foundation for the document draft that underwent several rounds of online discussion within the TF, and afterwards was also distributed to a broad group of stakeholders for collecting feedback. The list of generated competences was voted on during the TF meetings, while the level of agreement (LoA) with each statement was established by anonymous online voting. RESULTS: A total of 132 international training curricula were retrieved and extracted. In addition to the TF members, 253 stakeholders commented and voted on the competences through an online anonymous survey. The TF developed (1) an overarching framework indicating the areas that should be addressed during training, (2) 7 domains defining broad areas that rheumatology trainees should master by the end of the training programme, (3) 8 core themes defining the nuances of each domain and (4) 28 competences that trainees should acquire to cover each of the areas outlined in the overarching framework. A high LoA was achieved for all competences. CONCLUSION: These points to consider for EULAR-UEMS standards for the training of European rheumatologists are now defined. Their dissemination and use can hopefully contribute to harmonising training across European countries.

Neurophysiological and psychosocial mechanisms of fibromyalgia: A comprehensive review and call for an integrative model.

Research into the neurobiological and psychosocial mechanisms involved in fibromyalgia has progressed remarkably in recent years. Despite this, current accounts of fibromyalgia fail to capture the complex, dynamic, and mutual crosstalk between neurophysiological and psychosocial domains. We conducted a comprehensive review of the existing literature in order to: a) synthesize current knowledge on fibromyalgia; b) explore and highlight multi-level links and pathways between different systems; and c) build bridges connecting disparate perspectives. An extensive panel of international experts in neurophysiological and psychosocial aspects of fibromyalgia discussed the collected evidence and progressively refined and conceptualized its interpretation. This work constitutes an essential step towards the development of a model capable of integrating the main factors implicated in fibromyalgia into a single, unified construct which appears indispensable to foster the understanding, assessment, and intervention for fibromyalgia.

Boron as a Hypothetical Participant in the Prebiological Enantiomeric Enrichment.

Boron, as borate (or boric acid), is known as a mediator of the synthesis of ribose, ribonucleosides, and ribonucleotides (precursors of RNA) under plausible prebiotic conditions. With regard to these phenomena, the potential participation of this chemical element (as a constituent of minerals or hydrogels) for the emergence of prebiological homochirality is considered. This hypothesis is based on characteristics of crystalline surfaces as well as solubility of some minerals of boron in water or specific features of hydrogels with ester bonds from reaction of ribonucleosides and borate.

Safety and efficacy associated with long-term low-dose glucocorticoids in rheumatoid arthritis: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to assess the safety and efficacy of long-term low-dose glucocorticoids (GCs) in RA. METHODS: A protocolised systematic review and meta-analysis (PROSPERO No. CRD42021252528) of double-blind, placebo-controlled randomised trials (RCTs) comparing a low dose of GCs (≤ 7.5mg/day prednisone) to placebo over at least 2 years was performed. The primary outcome investigated was adverse events (AEs). We performed random-effects meta-analyses and used the Cochrane RoB tool and GRADE to assess risk of bias and quality of evidence (QoE). RESULTS: Six trials with 1078 participants were included. There was no evidence of an increased risk of AEs (incidence rate ratio 1.08; 95% CI 0.86, 1.34; P = 0.52); however, the QoE was low. The risks of death, serious AEs, withdrawals due to AEs, and AEs of special interest did not differ from placebo (very low to moderate QoE). Infections occurred more frequently with GCs (risk ratio 1.4; 1.19-1.65; moderate QoE). Concerning benefit, we found moderate to high quality evidence of improvement in disease activity (DAS28: -0.23; -0.43 to -0.03), function (HAQ -0.09; -0.18 to 0.00), and Larsen scores (-4.61; -7.52 to -1.69). In other efficacy outcomes, including Sharp van der Heijde scores, there was no evidence of benefits with GCs. CONCLUSION: There is very low to moderate QoE for no harm with long-term low dose GCs in RA, except for an increased risk of infections in GC users. The benefit-risk ratio might be reasonable forusing low-dose long-term GCs considering the moderate to high quality evidence for disease-modifying properties.