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Photoinduced chemical reactions and the development of new materials represent a current and significant topic. We present a sustainable and eco-friendly approach to the Knoevenagel condensation reaction involving carbonyl and active methylene compounds. Our method utilizes photo-activated carbon dots (CDs) derived from 5-hydroxymethylfurfural (5HMF) within an aqueous medium and does not require acidic, basic, or thermal conditions. This protocol operates effectively with aromatic, aliphatic, and heteroaromatic aldehydes and ketones. The 5HMF-derived-CDs can be reused four times without significant loss of activity. Moreover, this methodology is suitable for scaling up reactions, thereby highlighting its potential for industrial applications.

Objective: To determine the association between patient-reported spinal morning stiffness and lumbar disc degeneration (LDD) and systemic inflammation, as measured by C-reactive protein (CRP), in older patients with non-specific back pain. The ultimate objective is to help shape a future definition of spinal osteoarthritis (OA). Design: Baseline data from the Dutch “Back Complaints in the Older Adults” (BACE) study was used. The relationship between the severity and duration of patient-reported spinal morning stiffness, LDD (i.e., multilevel disc space narrowing and multilevel osteophytes), and CRP was assessed. Regression models adjusted for confounding variables were performed. Results: Six hundred and seventy-five patients were included. The mean age was 66.52 years (SD 7.69), with a mean CRP of 3.20 ​mg/L (SD 7.61). The severity of spinal morning stiffness was associated with multilevel disc space narrowing: OR 2.89 (95 ​% CI: 1.24 to 6.74) for ‘mild’, OR 2.97 (95 ​% CI: 1.18 to 7.44) for ‘moderate’, OR 3.23 (95 ​% CI: 1.17 to 8.90) for ‘severe’, and OR 5.62 (95 ​% CI: 1.70 to 18.60) for ‘extreme’ morning stiffness severity. However, spinal morning stiffness severity was not associated with multilevel osteophytes, and both multilevel features of LDD showed no associations with the duration of spinal morning stiffness. No associations were found between spinal morning stiffness severity or duration, and CRP levels. Conclusions: Our results suggest that the severity of patient-reported spinal morning stiffness might be considered in future definitions of symptomatic spinal OA and that spinal morning stiffness is probably a symptom of a degenerative process in the spine rather than a symptom of systemic inflammation in patients with back pain.

Objective: It is difficult for health care providers to diagnose structural spinal osteoarthritis (OA), because current guidelines recommend against imaging in patients with back pain. Therefore, the aim of this study was to develop and internally validate multivariable diagnostic prediction models based on a set of clinical and demographic features to be used for the diagnosis of structural spinal OA on lumbar radiographs in older patients with back pain. Design: Three diagnostic prediction models, for structural spinal OA on lumbar radiographs (i.e. multilevel osteophytes, multilevel disc space narrowing (DSN), and both combined), were developed and internally validated in the ‘Back Complaints in Older Adults’ (BACE) cohort (N ​= ​669). Model performance (i.e. overall performance, discrimination and calibration) and clinical utility (i.e. decision curve analysis) were assessed. Internal validation was performed by bootstrapping. Results: Mean age of the cohort was 66.9 years (±7.6 years) and 59% were female. All three models included age, gender, back pain duration and duration of spinal morning stiffness as predictors. The combined model additionally included restricted lateral flexion and spinal morning stiffness severity, and exhibited the best model performance (optimism adjusted c-statistic 0.661; good calibration with intercept −0.030 and slope of 0.886) and acceptable clinical utility. The other models showed suboptimal discrimination, good calibration and acceptable decision curves. Conclusion: All three models for structural spinal OA displayed lesuboptimal discrimination and need improvement. However, these internally validated models have potential to inform primary care clinicians about a patient with risk of having structural spinal OA on lumbar radiographs. External validation before implementation in clinical care is recommended.

BackgroundChronic noncancer pain (CNCP) is highly present among older adults, affecting their physical, psychological, and social functioning. A biopsychosocial multimodal approach to CNCP management is currently extensively suggested by international clinical practice guidelines. Recently, the growing development and application of eHealth within pain management has yielded encouraging results in terms of effectiveness and feasibility; however, its use among the older population remains underexamined. ObjectiveThe overall aim of this scoping review was to systematically map existing literature about eHealth multimodal interventions (including both physical and psychosocial components) targeting older adults with CNCP. MethodsThis review adhered to the JBI methodology, a protocol was a priori registered as a preprint on the medRxiv platform, and the results were reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Four electronic databases (PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and PsycINFO) were systematically searched for relevant articles. Studies were included if they reported on multimodal interventions (including both physical and psychosocial components) delivered through any eHealth modality to an older population with any type of CNCP. Two reviewers selected the studies: first by screening titles and abstracts and second by screening full-text articles. The quality of the included studies was evaluated using the Quality Assessment Tool for Studies with Diverse Designs. The results of the studies were summarized narratively. ResultsA total of 9 studies (n=6, 67% published between 2021 and 2023) with quality rated as medium to high were included, of which 7 (78%) were randomized controlled trials (n=5, 71% were pilot and feasibility studies). All the included studies evaluated self-management interventions, most of them (n=7, 78%) specifically designed for older adults. The participants were aged between 65 and 75 years on average (mean 68.5, SD 3.5 y) and had been diagnosed with different types of CNCP (eg, osteoarthritis and chronic low back pain). Most of the included studies (5/9, 56%) involved the use of multiple eHealth modalities, with a higher use of web-based programs and video consulting. Only 1 (11%) of the 9 studies involved a virtual reality–based intervention. The evaluated interventions showed signs of effectiveness in the targeted biopsychosocial outcomes, and the participants’ engagement and ratings of satisfaction were generally positive. However, several research gaps were identified and discussed. ConclusionsOverall, of late, there has been a growing interest in the potential that eHealth multimodal interventions offer in terms of improving pain, physical, and psychosocial outcomes in older adults with CNCP. However, existing literature on this topic still seems scarce and highly heterogeneous, with few proper randomized controlled trials, precluding robust conclusions. Several gaps emerged in terms of the older population considered and the lack of evaluation of comorbidities. International Registered Report Identifier (IRRID)RR2-10.1101/2023.07.27.23293235

There is increasing recognition of the need for researchers to collect and report data that can illuminate health inequities. In pain research, routinely collecting equity-relevant data has the potential to inform about the generalisability of findings; whether the intervention has differential effects across strata of society; or it could be used to guide population targeting for clinical studies. Developing clarity and consensus on what data should be collected and how to collect it is required to prompt researchers to further consider equity issues in the planning, conduct, interpretation, and reporting of research. The overarching aim of the ‘Identifying Social Factors that Stratify Health Opportunities and Outcomes’ (ISSHOOs) in pain research project is to provide researchers in the pain field with recommendations to guide the routine collection of equity-relevant data. The design of this project is consistent with the methods outlined in the ‘Guidance for Developers of Health Research Reporting Guidelines’ and involves 4 stages: (i) Scoping review; (ii) Delphi Study; (iii) Consensus Meeting; and (iv) Focus Groups. This stakeholder-engaged project will produce a minimum dataset that has global, expert consensus. Results will be disseminated along with explanation and elaboration as a crucial step towards facilitating future action to address avoidable disparities in pain outcomes.

Abstract. Introduction:. Many people worldwide suffer from chronic pain. Improving our knowledge on chronic pain prevalence and management requires methods to collect pain self-reports in large populations. Smartphone-based tools could aid data collection by allowing people to use their own device, but the measurement properties of such tools are largely unknown. Objectives:. To assess the reliability, validity, and responsiveness of a smartphone-based manikin to support pain self-reporting. Methods:. We recruited people with fibromyalgia, rheumatoid arthritis, and/or osteoarthritis and access to a smartphone and the internet. Data collection included the Global Pain Scale at baseline and follow-up, and 30 daily pain drawings completed on a 2-dimensional, gender-neutral manikin. After deriving participants' pain extent from their manikin drawings, we evaluated convergent and discriminative validity, test–retest reliability, and responsiveness and assessed findings against internationally agreed criteria for good measurement properties. Results:. We recruited 131 people; 104 were included in the full sample, submitting 2185 unique pain drawings. Manikin-derived pain extent had excellent test–retest reliability (intraclass correlation coefficient, 0.94), moderate convergent validity (ρ, 0.46), and an ability to distinguish fibromyalgia and osteoarthritis from rheumatoid arthritis (F statistics, 30.41 and 14.36, respectively; P < 0.001). Responsiveness was poor (ρ, 0.2; P, 0.06) and did not meet the respective criterion for good measurement properties. Conclusion:. Our findings suggest that smartphone-based manikins can be a reliable and valid method for pain self-reporting, but that further research is warranted to explore, enhance, and confirm the ability of such manikins to detect a change in pain over time.

Abstract Background Core outcome sets (COSs) aim to reduce outcome heterogeneity in clinical practice and research by suggesting a minimum number of agreed-upon outcomes in clinical trials. Most COSs in the musculoskeletal field are developed for specific conditions. We propose that there are likely to be common core domains within existing musculoskeletal COSs that may be used as a starting point in the development of future COSs. We aim to identify common core domains from existing COSs and to facilitate the development of new COSs for musculoskeletal conditions. As a secondary aim, we will assess the development quality of these COSs. Methods A systematic review including musculoskeletal COSs. We will search Core Outcome Measures in Effectiveness Trials (COMET) database, MEDLINE, EMBASE, Scopus, Cochrane Methodology Register and International Consortium for Health Outcome Measurement (ICHOM). Studies will be included if related to the development of a COS in adults with musculoskeletal conditions and for any type of intervention. Quality will be assessed using the Core Outcome Set-Standards for Development (COS-STAD) recommendations. Data extracted will include scope of the COS, health condition, interventions and outcome domains. Primary outcomes will be all core domains recommended within each COS. We define a common core outcome domain as one present in at least 67% of all COSs. All findings will be summarized and presented using descriptive statistics. Discussion This systematic review of COSs will describe the core domains recommended within each musculoskeletal COS. Common domains found may be used in the initial stages of development of future musculoskeletal COSs. Systematic review registration PROSPERO CRD42021239141

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Background As management of chronic pain continues to be suboptimal, there is a need for tools that support frequent, longitudinal pain self-reporting to improve our understanding of pain. This study aimed to assess the feasibility and acceptability of daily pain self-reporting using a smartphone-based pain manikin. Methods For this prospective feasibility study, we recruited adults with lived experience of painful musculoskeletal condition. They were asked to complete daily pain self-reports via an app for 30 days. We assessed feasibility by calculating pain report completion levels, and investigated differences in completion levels between subgroups. We assessed acceptability via an end-of-study questionnaire, which we analysed descriptively. Results Of the 104 participants, the majority were female ( n = 87; 84%), aged 45-64 ( n = 59; 57%), and of white ethnic background ( n = 89; 86%). The mean completion levels was 21 (± 7.7) pain self-reports. People who were not working (odds ratio (OR) = 1.84; 95% confidence interval (CI), 1.52-2.23) were more likely, and people living in less deprived areas (OR = 0.77; 95% CI, 0.62-0.97) and of non-white ethnicity (OR = 0.45; 95% CI, 0.36-0.57) were less likely to complete pain self-reports than their employed, more deprived and white counterparts, respectively. Of the 96 participants completing the end-of-study questionnaire, almost all participants agreed that it was easy to complete a pain drawing ( n = 89; 93%). Conclusion It is feasible and acceptable to self–report pain using a smartphone–based manikin over a month. For its wider adoption for pain self–reporting, the feasibility and acceptability should be further explored among people with diverse socio–economic and ethnic backgrounds.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that progressively affects motoneurons, causing muscle atrophy and evolving to death. Astrocytes inhibit the expression of MHC-I by neurons, contributing to a degenerative outcome. The present study verified the influence of interferon β (IFN β) treatment, a proinflammatory cytokine that upregulates MHC-I expression, in SOD1G93A transgenic mice. For that, 17 days old presymptomatic female mice were subjected to subcutaneous application of IFN β (250, 1,000, and 10,000 IU) every other day for 20 days. Rotarod motor test, clinical score, and body weight assessment were conducted every third day throughout the treatment period. No significant intergroup variations were observed in such parameters during the pre-symptomatic phase. All mice were then euthanized, and the spinal cords collected for comparative analysis of motoneuron survival, reactive gliosis, synapse coverage, microglia morphology classification, cytokine analysis by flow cytometry, and RT–qPCR quantification of gene transcripts. Additionally, mice underwent Rotarod motor assessment, weight monitoring, and neurological scoring. The results show that IFN β treatment led to an increase in the expression of MHC-I, which, even at the lowest dose (250 IU), resulted in a significant increase in neuronal survival in the ALS presymptomatic period which lasted until the onset of the disease. The treatment also influenced synaptic preservation by decreasing excitatory inputs and upregulating the expression of AMPA receptors by astrocytes. Microglial reactivity quantified by the integrated density of pixels did not decrease with treatment but showed a less activated morphology, coupled with polarization to an M1 profile. Disease progression upregulated gene transcripts for pro- and anti-inflammatory cytokines, and IFN β treatment significantly decreased mRNA expression for IL4. Overall, the present results demonstrate that a low dosage of IFN β shows therapeutic potential by increasing MHC-I expression, resulting in neuroprotection and immunomodulation.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective and progressive loss of motor neurons from the spinal cord, brain stem, and motor cortex. Although the hallmark of ALS is motor neuron degeneration, astrocytes, microglia, and T cells actively participate. Pharmacological treatment with riluzole has little effect on the lifespan of the patient. Thus, the development of new therapeutic strategies is of utmost importance. The objective of this study was to verify whether human mesenchymal stem cells (hMSCs) from adipose tissue have therapeutic potential in SOD1G93A transgenic mice. The treatment was carried out in the asymptomatic phase of the disease (10th week) by a single systemic application of ad-hMSCs (1 ×105 cells). The animals were sacrificed at the 14th week (the initial stage of symptoms) or the end-stage (ES) of the disease. The lumbar spinal cords were dissected and processed for Nissl staining (neuronal survival), immunohistochemistry (gliosis and synaptic preservation), and gene transcript expression (qRT–PCR). Behavioral analyses considering the onset of disease and its progression, neurological score, body weight, and motor control (rotarod test) started on the 10th week and were performed every three days until the ES of the disease. The results revealed that treatment with ad-hMSCs promoted greater neuronal survival (44%) than vehicle treatment. However, no effect was seen at the ES of the disease. Better structural preservation of the ventral horn in animals treated with ad-hMSCs was observed, together with decreased gliosis and greater synapse protection. In line with this, we found that the transcript levels of Hgf1 were upregulated in ad-hMSCs-treated mice. These results corroborate the behavioral data showing that ad-hMSCs had delayed motor deficits and reduced weight loss compared to vehicle animals. Additionally, cell therapy delayed the course of the disease and significantly improved survival by 20 days. Overall, our results indicate that treatment with ad-hMSCs has beneficial effects, enhancing neuronal survival and promoting a less degenerative neuronal microenvironment. Thus, this may be a potential therapy to improve the quality of life and to extend the lifespan of ALS patients.

Abstract Carbon dots (CDs) samples were synthesized from orange peel waste (OPW) via a simple and eco‐friendly hydrothermal carbonization (HTC) and electrochemical (EC) bottom‐up synthesis integrated approach. The comprehensive chemical‐physical characterization of CDs samples, carried out by various techniques such as TEM, EDX, XRD, FT‐IR, underlined their morphological and microstructural features. The CDs exhibited attractive electrochemical properties, and thus an electrochemical sensor by modifying a screen printed carbon electrode (CDs/SPCE) for the detection of nitrobenzene (NB) in water was developed. Electroanalytical performances of CDs/SPCE sensor using differential pulse voltammetry (DPV) demonstrated its high sensitivity (9.36 μA μM−1 cm−2) towards NB in a wide linear dynamic range (0.1–2000 μM) and a low limit of detection (LOD=13 nM). The electrochemical sensor also shown high selectivity, long‐term stability, and repeatability. This paper might open the way to a new synergistic HTC‐EC approach for the synthesis of CDs from waste biomass material and their advanced application in highly efficient electrochemical sensors.

Abstract Background Back pain is an extensive burden to our healthcare system, yet few studies have explored modifiable prognostic factors associated with high costs related to healthcare utilization, especially among older back pain patients. The aims of this study were to identify modifiable prognostic factors for high costs related to healthcare utilization among older people seeking primary care with a new episode of back pain; and to replicate the identified associations in a similar cohort, in a different country. Methods Data from two cohort studies within the BACE consortium were used, including 452 and 675 people aged ≥55 years seeking primary care with a new episode of back pain. High costs were defined as costs in the top 25th percentile. Healthcare utilization was self-reported, aggregated for one-year of follow-up and included: primary care consultations, medications, examinations, hospitalization, rehabilitation stay and operations. Costs were estimated based on unit costs collected from national pricelists. Nine potential modifiable prognostic factors were selected based on previous literature. Univariable and multivariable binary logistic regression models were used to identify and replicate associations (crude and adjusted for selected covariates) between each modifiable prognostic factor and high costs related to healthcare utilization. Results Four modifiable prognostic factors associated with high costs related to healthcare utilization were identified and replicated: a higher degree of pain severity, disability, depression, and a lower degree of physical health-related quality of life. Kinesiophobia and recovery expectations showed no prognostic value. There were inconsistent results across the two cohorts with regards to comorbidity, radiating pain below the knee and mental health-related quality of life. Conclusion The factors identified in this study may be future targets for intervention with the potential to reduce high costs related to healthcare utilization among older back pain patients. Trial registration ClinicalTrials.gov NCT04261309, 07 February 2020. Retrospectively registered.