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1.
J Am Chem Soc ; 146(9): 6217-6224, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38382047

ABSTRACT

In this study, we present an efficient approach for the depolymerization of poly(methyl methacrylate) (PMMA) copolymers synthesized via conventional radical polymerization. By incorporating low mol % phthalimide ester-containing monomers during the polymerization process, colorless and transparent polymers closely resembling unfunctionalized PMMA are obtained, which can achieve >95% reversion to methyl methacrylate (MMA). Notably, our catalyst-free bulk depolymerization method exhibits exceptional efficiency, even for high-molecular-weight polymers, including ultrahigh-molecular-weight (106-107 g/mol) PMMA, where near-quantitative depolymerization is achieved. Moreover, this approach yields polymer byproducts of significantly lower molecular weight, distinguishing it from bulk depolymerization methods initiated from chain ends. Furthermore, we extend our investigation to polymethacrylate networks, demonstrating high extents of depolymerization. This innovative depolymerization strategy offers promising opportunities for the development of sustainable polymethacrylate materials, holding great potential for various applications in polymer science.

2.
Osteoarthritis Cartilage ; 32(2): 159-165, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38035975

ABSTRACT

OBJECTIVE: To highlight some important findings from osteoarthritis (OA) epidemiology and therapy research undertaken over the past year. METHODS: Search of MEDLINE and EMBASE databases between April 1, 2022 to March 3, 2023 using "exp *Osteoarthritis/" as the preliminary search term. The search was limited to articles published in English and including human subjects. Final inclusions were based on perceived importance and results that may inform improved identification of risk factors or OA treatments, as well as OA subgroups of potential relevance to risk factors or treatment approaches. RESULTS: 3182 studies were screened, leaving 208 eligible for inclusion. This narrative review of thirty-three selected studies was arranged into: a) OA predictors - population-based studies, b) Specific predictors of OA and OA outcome; c) Intra-articular injections, and d) OA phenotypes. There was some suggestion of sex differences in predictors of incidence or outcomes. Body mass index changes appear largely to affect knee OA outcomes. Evidence points to a lack of benefit of viscosupplementation in knee OA; findings were variable for other injectables. Studies of OA phenotypes reveal potentially relevant clinical and pathophysiological differences. CONCLUSIONS: Identifying risk factors for the incidence/progression of OA represents an ongoing and important area of OA research. Sex may play a role in this understanding and bears consideration and further study. For knee injectables other than viscosupplementation, additional high-quality trials appear warranted. Continued investigation and application of phenotyping across the OA disease, illness and care spectrum may be key to developing disease-modifying agents and their appropriate selection for individuals.


Subject(s)
Osteoarthritis, Knee , Viscosupplementation , Humans , Female , Male , Hyaluronic Acid , Osteoarthritis, Knee/therapy , Osteoarthritis, Knee/drug therapy , Viscosupplementation/methods , Injections, Intra-Articular , Knee Joint
3.
J Rheumatol ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38879187

ABSTRACT

OBJECTIVE: Difficulty walking is a primary reason that individuals with knee osteoarthritis (OA) seek care. We examined the change in self-reported difficulty walking after participating in the Good Life With Osteoarthritis in Denmark (GLA:D) 8-week education and exercise program and assessed patient factors associated with improvement in difficulty walking. METHODS: This was a registry-based cohort study of individuals in Denmark with knee OA who enrolled in GLA:D. Assessments were administered at baseline, program completion (~3 months), and 12 months. Our prespecified primary outcome was change in self-reported difficulty walking assessed using the EuroQol 5-dimension 5-level walking item. Exposures included sociodemographic factors, measures of OA illness severity, comorbidities, and psychological factors. In those with baseline moderate/severe difficulty walking, using multivariable regression analysis, we assessed the relationship between exposures of interest and improvement to no/slight difficulty walking. RESULTS: We included 5262 participants. Of 2178 (41.4%) individuals with baseline moderate/severe difficulty walking, 51.4% and 58.3% reported no/slight difficulty walking at 3 and 12 months, respectively. Greater self-efficacy, younger age, female sex, lower BMI, less intense knee pain, and better function at baseline were associated with greater likelihood of improvement in difficulty walking, whereas severe difficulty walking at baseline and back pain intensity were associated with decreased likelihood of improvement. CONCLUSION: More than half of those with baseline difficulty walking experienced substantial improvement after completing GLA:D and this improvement was maintained at 12 months. Several patient factors were associated with the outcome, suggesting that some individuals may require additional support and extended treatment.

4.
Epilepsy Behav ; 152: 109659, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38301454

ABSTRACT

Depression is prevalent in epilepsy patients and their intracranial brain activity recordings can be used to determine the types of brain activity that are associated with comorbid depression. We performed case-control comparison of spectral power and phase amplitude coupling (PAC) in 34 invasively monitored drug resistant epilepsy patients' brain recordings. The values of spectral power and PAC for one-minute segments out of every hour in a patient's study were correlated with pre-operative assessment of depressive symptoms by Beck Depression Inventory-II (BDI). We identified an elevated PAC signal (theta-alpha-beta phase (5-25 Hz)/gamma frequency (80-100 Hz) band) that is present in high BDI scores but not low BDI scores adult epilepsy patients in brain regions implicated in primary depression, including anterior cingulate cortex, amygdala and orbitofrontal cortex. Our results showed the application of PAC as a network-specific, electrophysiologic biomarker candidate for comorbid depression and its potential as treatment target for neuromodulation.


Subject(s)
Brain Waves , Epilepsy , Adult , Humans , Depression/diagnosis , Depression/etiology , Epilepsy/complications , Epilepsy/diagnosis , Brain , Brain Waves/physiology , Prefrontal Cortex , Electroencephalography
5.
Pain Med ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38741219

ABSTRACT

OBJECTIVE: We evaluated whether more severe back pain phenotypes-persistent, frequent or disabling back pain-are associated with higher mortality among older men. METHODS: In this secondary analysis of a prospective cohort, the Osteoporotic Fractures in Men (MrOS) study, we evaluated mortality rates by back pain phenotype among 5215 older community-dwelling men (mean age, 73 years, SD = 5.6) from six U.S. sites. The primary back pain measure used baseline and year five back pain questionnaire data to characterize participants as having: no back pain; non-persistent back pain; infrequent persistent back pain; or frequent persistent back pain. Secondary measures of back pain from year five questionnaire included disabling back pain phenotypes. The main outcomes measured were all-cause and cause-specific mortality. RESULTS: After the year five exam, during up to 18 years of follow-up (mean follow-up=10.3 years), there were 3513 deaths (1218 cardiovascular, 764 cancer, 1531 other). A higher proportion of men with frequent persistent back pain versus no back pain died (78% versus 69%; sociodemographic-adjusted HR = 1.27, 95%CI=1.11-1.45). No association was evident after further adjusting for health-related factors such as self-reported general health and comorbid chronic health conditions (fully-adjusted HR = 1.00; 95%CI=0.86-1.15). Results were similar for cardiovascular mortality and other mortality, but we observed no association of back pain with cancer mortality. Secondary back pain measures including back-related disability were associated with increased mortality risk that remained statistically significant in fully-adjusted models. CONCLUSION: While frequent persistent back pain was not independently associated with mortality in older men, additional secondary disabling back pain phenotypes were independently associated with increased mortality. Future investigations should evaluate whether improvements in disabling back pain effect general health and well-being or mortality.

6.
Health Expect ; 27(2): e14022, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38528661

ABSTRACT

BACKGROUND: This study investigated healthcare access and quality for people who are transgender and gender-diverse (PTGD) in Saskatchewan (SK), Canada, to inform a larger project that was piloting two peer health navigators for PTGD. METHODS: Two online focus groups were held. Nineteen participants were recruited to represent a broad range in age, gender and location in SK. Transcripts of the focus groups were analyzed using a thematic approach. RESULTS: The core theme that was identified was participants' desire for culturally safe healthcare. This core theme had two component themes: (1) systemic healthcare factors and (2) individual healthcare provider (HCP) factors. The healthcare system primarily acted as a barrier to culturally safe healthcare. HCPs could be either barriers or facilitators of culturally safe care; however, negative experiences outweighed positive ones. CONCLUSIONS: PTGD in SK face discrimination, with delays and barriers to care at all levels of the healthcare system. Peer health navigators can address some of these discrepancies; however, greater support is required for PTGD to be able to access culturally safe healthcare. PATIENT OR PUBLIC CONTRIBUTION: People with lived experience/PTGD were involved in all stages of this project. They were included on the team as community researchers and co-developed the research project, conducted the focus groups, participated in the analyses and are co-authors. As well, both navigators and all the participants in the focus groups were also PTGD.


Subject(s)
Transgender Persons , Humans , Focus Groups , Saskatchewan , Qualitative Research , Health Services
7.
Proc Natl Acad Sci U S A ; 118(51)2021 12 21.
Article in English | MEDLINE | ID: mdl-34903661

ABSTRACT

Local blood flow control within the central nervous system (CNS) is critical to proper function and is dependent on coordination between neurons, glia, and blood vessels. Macroglia, such as astrocytes and Müller cells, contribute to this neurovascular unit within the brain and retina, respectively. This study explored the role of microglia, the innate immune cell of the CNS, in retinal vasoregulation, and highlights changes during early diabetes. Structurally, microglia were found to contact retinal capillaries and neuronal synapses. In the brain and retinal explants, the addition of fractalkine, the sole ligand for monocyte receptor Cx3cr1, resulted in capillary constriction at regions of microglial contact. This vascular regulation was dependent on microglial Cx3cr1 involvement, since genetic and pharmacological inhibition of Cx3cr1 abolished fractalkine-induced constriction. Analysis of the microglial transcriptome identified several vasoactive genes, including angiotensinogen, a constituent of the renin-angiotensin system (RAS). Subsequent functional analysis showed that RAS blockade via candesartan abolished microglial-induced capillary constriction. Microglial regulation was explored in a rat streptozotocin (STZ) model of diabetic retinopathy. Retinal blood flow was reduced after 4 wk due to reduced capillary diameter and this was coincident with increased microglial association. Functional assessment showed loss of microglial-capillary response in STZ-treated animals and transcriptome analysis showed evidence of RAS pathway dysregulation in microglia. While candesartan treatment reversed capillary constriction in STZ-treated animals, blood flow remained decreased likely due to dilation of larger vessels. This work shows microglia actively participate in the neurovascular unit, with aberrant microglial-vascular function possibly contributing to the early vascular compromise during diabetic retinopathy.


Subject(s)
Chemokine CX3CL1/metabolism , Diabetic Retinopathy/pathology , Microglia/physiology , Retina/pathology , Animals , Benzimidazoles/pharmacology , Biphenyl Compounds/pharmacology , Chemokine CX3CL1/pharmacology , Diabetic Retinopathy/chemically induced , Diabetic Retinopathy/metabolism , Gene Expression Profiling , Mice , Microglia/metabolism , Neurons/physiology , Pericytes/pathology , Rats , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/genetics , Retina/metabolism , Retinal Vessels/drug effects , Retinal Vessels/pathology , Signal Transduction/drug effects , Streptozocin/pharmacology , Tetrazoles/pharmacology , Vasoconstriction/drug effects
8.
J Arthroplasty ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38697319

ABSTRACT

BACKGROUND: Total hip arthroplasty (THA) for osteoarthritis (OA) is a major health system cost. Education and exercise (Edu + Ex) programs may reduce the number of THAs needed, but supporting data are limited. This study aimed to estimate the treatment effect of THA versus Edu + Ex on pain, function, and quality of life outcomes 3 and 12 months after treatment initiation for hip OA. METHODS: Patients who had hip OA who underwent THA or an Edu + Ex program were included in this propensity-matched study. In 778 patients (Edu + Ex, n = 303; THA, n = 475), propensity scores were based on pretreatment characteristics, and patients were matched on a 1:1 ratio. Between-group treatment effects (pain, function, and quality of life) were estimated as the mean difference (MD) in change from pretreatment to 3-month and 12-month follow-up using linear mixed models. RESULTS: The matched sample consisted of 266 patients (Edu + Ex, n = 133; THA, n = 133) who were balanced on all pretreatment characteristics except opioid use. At 12-month follow-up, THA resulted in significantly greater improvements in pain (MD 35.4; 95% confidence interval [CI] 31.4 to 39.4), function (MD 30.5; 95% CI 26.3 to 34.7), and quality of life (MD 33.6; 95% CI 28.8 to 38.4). Between 17% and 30% of patients receiving Edu + Ex experienced a surgical threshold for clinically meaningful improvement in outcomes, compared to 84% and 90% of THA patients. CONCLUSIONS: A THA provides greater improvements in pain, function, and quality of life. A notable proportion of Edu + Ex patients had clinically meaningful improvements, suggesting Edu + Ex may result in THA deferral in some patients, but confirmatory trials are needed.

9.
Trop Anim Health Prod ; 56(5): 166, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758410

ABSTRACT

African Swine Fever (ASF) disease transmission parameters are crucial for making response and control decisions when faced with an outbreak, yet they are poorly quantified for smallholder and village contexts within Southeast Asia. Whilst disease-specific factors - such as latent and infectious periods - should remain reasonably consistent, host, environmental and management factors are likely to affect the rate of disease spread. These differences are investigated using Approximate Bayesian Computation with Sequential Monte-Carlo methods to provide disease parameter estimates in four naïve pig populations in villages of Lao People's Democratic Republic. The villages represent smallholder pig farmers of the Northern province of Oudomxay and the Southern province of Savannakhet, and the model utilised field mortality data to validate the transmission parameter estimates over the course of multiple model generations. The basic reproductive number between-pigs was estimated to range from 3.08 to 7.80, whilst the latent and infectious periods were consistent with those published in the literature for similar genotypes in the region (4.72 to 6.19 days and 2.63 to 5.50 days, respectively). These findings demonstrate that smallholder village pigs interact similarly to commercial pigs, however the spread of disease may occur slightly slower than in commercial study groups. Furthermore, the findings demonstrated that despite diversity across the study groups, the disease behaved in a consistent manner. This data can be used in disease control programs or for future modelling of ASF in smallholder contexts.


Subject(s)
African Swine Fever , Bayes Theorem , Animals , African Swine Fever/transmission , African Swine Fever/epidemiology , Swine , Laos/epidemiology , Basic Reproduction Number , Animal Husbandry/methods , Monte Carlo Method , Sus scrofa , African Swine Fever Virus/physiology , Disease Outbreaks/veterinary
10.
Angew Chem Int Ed Engl ; : e202408592, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007541

ABSTRACT

We describe a methodology of post-polymerization functionalization to enable subsequent bulk depolymerization to monomer by utilizing mechanochemical macro-radical generation. By harnessing ultrasonic chain-scission in the presence of N-hydroxyphthalimide methacrylate (PhthMA), we successfully chain-end functionalize polymers to promote subsequent depolymerization in bulk, achieving up to 81% depolymerization of poly(methyl methacrylate) (PMMA) and poly(α-methylstyrene) (PAMS) within 30 min. This method of depolymerization yields a high-purity monomer that can be repolymerized. Moreover, as compared to the most common methods of depolymerization, this work is most efficient with ultra-high molecular weight (UHMW) polymers, establishing a method with the potential to address highly persistent, non-degradable all-carbon backbone plastic materials. Lastly, we demonstrate the expansion of this depolymerization method to commercial cell cast PMMA, achieving high degrees of depolymerization from post-consumer waste. This work is the first demonstration of applying PhthMA-promoted depolymerization strategies in homopolymer PMMA and PAMS prepared by conventional polymerization methods.

11.
Angew Chem Int Ed Engl ; 63(20): e202403026, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38416815

ABSTRACT

We demonstrate that electrochemical-induced decarboxylation enables reliable post-polymerization modification and degradation of polymers. Polymers containing N-(acryloxy)phthalimides were subjected to electrochemical decarboxylation under mild conditions, which led to the formation of transient alkyl radicals. By installing these redox-active units, we systematically modified the pendent groups and chain ends of polyacrylates. This approach enabled the production of poly(ethylene-co-methyl acrylate) and poly(propylene-co-methyl acrylate) copolymers, which are difficult to synthesize by direct polymerization. Spectroscopic and chromatographic techniques reveal these transformations are near-quantitative on several polymer systems. Electrochemical decarboxylation also enables the degradation of all-methacrylate poly(N-(methacryloxy)phthalimide-co-methyl methacrylate) copolymers with a degradation efficiency of >95 %. Chain cleavage is achieved through the decarboxylation of the N-hydroxyphthalimide ester and subsequent ß-scission of the backbone radical. Electrochemistry is thus shown to be a powerful tool in selective polymer transformations and controlled macromolecular degradation.

12.
Br J Haematol ; 203(5): 840-851, 2023 12.
Article in English | MEDLINE | ID: mdl-37614192

ABSTRACT

Comorbidity assessment before allogeneic haematopoietic cell transplantation (allo-HCT) is essential for estimating non-relapse mortality (NRM) risk. We previously developed the Simplified Comorbidity Index (SCI), which captures a small number of 'high-yield' comorbidities and older age. The SCI was predictive of NRM in myeloablative CD34-selected allo-HCT. Here, we evaluated the SCI in a single-centre cohort of 327 patients receiving reduced-intensity conditioning followed by unmanipulated allografts from HLA-matched donors. Among the SCI factors, age above 60, mild renal impairment, moderate pulmonary disease and cardiac disease were most frequent. SCI scores ranged from 0 to 8, with 39%, 20%, 20% and 21% having scores of 0-1, 2, 3 and ≥4 respectively. Corresponding cumulative incidences of 3-year NRM were 11%, 16%, 22% and 27%; p = 0.03. In multivariable models, higher SCI scores were associated with incremental risks of all-cause mortality and NRM. The SCI had an area under the receiver operating characteristic curve of 65.9%, 64.1% and 62.9% for predicting 1-, 2- and 3-year NRM versus 58.4%, 60.4% and 59.3% with the haematopoietic cell transplantation comorbidity index. These results demonstrate for the first time that the SCI is predictive of NRM in patients receiving allo-HCT from HLA-matched donors after reduced-intensity conditioning.


Subject(s)
Hematopoietic Stem Cell Transplantation , Tissue Donors , Humans , Comorbidity , Hematopoietic Stem Cell Transplantation/methods , Recurrence , Retrospective Studies , Transplantation Conditioning/methods , Transplantation, Homologous/methods , Mortality
13.
J Cardiovasc Electrophysiol ; 34(9): 1914-1924, 2023 09.
Article in English | MEDLINE | ID: mdl-37522254

ABSTRACT

AIMS: To investigate the association of cardiac resynchronization therapy (CRT) on outcomes among participants with and without a history of atrial fibrillation (AF). METHODS: Individual-patient-data from four randomized trials investigating CRT-Defibrillators (COMPANION, MADIT-CRT, REVERSE) or CRT-Pacemakers (COMPANION, MIRACLE) were analyzed. Outcomes were time to a composite of heart failure hospitalization or all-cause mortality or to all-cause mortality alone. The association of CRT on outcomes for patients with and without a history of AF was assessed using a Bayesian-Weibull survival regression model adjusting for baseline characteristics. RESULTS: Of 3964 patients included, 586 (14.8%) had a history of AF; 2245 (66%) were randomized to CRT. Overall, CRT reduced the risk of the primary composite endpoint (hazard ratio [HR]: 0.69, 95% credible interval [CI]: 0.56-0.81). The effect was similar (posterior probability of no interaction = 0.26) in patients with (HR: 0.78, 95% CI: 0.55-1.10) and without a history of AF (HR: 0.67, 95% CI: 0.55-0.80). In these four trials, CRT did not reduce mortality overall (HR: 0.82, 95% CI: 0.66-1.01) without evidence of interaction (posterior probability of no interaction = 0.14) for patients with (HR: 1.09, 95% CI: 0.70-1.74) or without a history of AF (HR: 0.70, 95% CI: 0.60-0.97). CONCLUSION: The association of CRT on the composite endpoint or mortality was not statistically different for patients with or without a history of AF, but this could reflect inadequate power. Our results call for trials to confirm the benefit of CRT recipients with a history of AF.


Subject(s)
Atrial Fibrillation , Cardiac Resynchronization Therapy , Defibrillators, Implantable , Heart Failure , Humans , Atrial Fibrillation/diagnosis , Atrial Fibrillation/therapy , Cardiac Resynchronization Therapy/methods , Bayes Theorem , Treatment Outcome , Heart Failure/diagnosis , Heart Failure/therapy
14.
Epilepsia ; 64(10): 2725-2737, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37452760

ABSTRACT

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is associated with mortality in persons with comorbidities. The aim of this study was to evaluate in-hospital outcomes in patients with COVID-19 with and without epilepsy. METHODS: We conducted a retrospective study of patients with COVID-19 admitted to a multicenter health system between March 15, 2020, and May 17, 2021. Patients with epilepsy were identified using a validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM case definition. Logistic regression models and Kaplan-Meier analyses were conducted for mortality and non-routine discharges (i.e., not discharged home). An ordinary least-squares regression model was fitted for length of stay (LOS). RESULTS: We identified 9833 people with COVID-19 including 334 with epilepsy. On univariate analysis, people with epilepsy had significantly higher ventilator use (37.70% vs 14.30%, p < .001), intensive care unit (ICU) admissions (39.20% vs 17.70%, p < .001) mortality rate (29.60% vs 19.90%, p < .001), and longer LOS (12 days vs 7 days, p < .001). and fewer were discharged home (29.64% vs 57.37%, p < .001). On multivariate analysis, only non-routine discharge (adjusted odds ratio [aOR] 2.70, 95% confidence interval [CI] 2.00-3.70; p < .001) and LOS (32.50% longer, 95% CI 22.20%-43.60%; p < .001) were significantly different. Factors associated with higher odds of mortality in epilepsy were older age (aOR 1.05, 95% CI 1.03-1.08; p < .001), ventilator support (aOR 7.18, 95% CI 3.12-16.48; p < .001), and higher Charlson comorbidity index (CCI) (aOR 1.18, 95% CI 1.04-1.34; p = .010). In epilepsy, admissions between August and December 2020 or January and May 2021 were associated with a lower odds of non-routine discharge and decreased LOS compared to admissions between March and July 2020, but this difference was not statistically significant. SIGNIFICANCE: People with COVID-19 who had epilepsy had a higher odds of non-routine discharge and longer LOS but not higher mortality. Older age (≥65), ventilator use, and higher CCI were associated with COVID-19 mortality in epilepsy. This suggests that older adults with epilepsy and multimorbidity are more vulnerable than those without and should be monitored closely in the setting of COVID-19.


Subject(s)
COVID-19 , Epilepsy , Humans , Aged , Cohort Studies , Retrospective Studies , Length of Stay , Epilepsy/epidemiology , Hospitals , Hospital Mortality
15.
J Immunol ; 207(1): 34-43, 2021 07 01.
Article in English | MEDLINE | ID: mdl-34108258

ABSTRACT

Systemic lupus erythematosus (SLE) is associated with an IL-2-deficient state, with regulatory T cells (Tregs) showing diminished immune regulatory capacity. A low dose of IL-2 has shown encouraging clinical benefits in SLE patients; however, its clinical utility is limited because of the requirement of daily injections and the observation of increase in proinflammatory cytokines and in non-Tregs. We recently showed that a fusion protein of mouse IL-2 and mouse IL-2Rα (CD25), joined by a noncleavable linker, was effective in treating diabetes in NOD mice by selectively inducing Treg expansion. In this report, we show that mouse IL-2 (mIL-2)/CD25 at doses up to 0.5 mg/kg twice a week induced a robust Treg expansion without showing signs of increase in the numbers of NK, CD4+Foxp3-, or CD8+ T cells or significant increase in proinflammatory cytokines. In both NZB × NZW and MRL/lpr mice, mIL-2/CD25 at 0.2-0.4 mg/kg twice a week demonstrated efficacy in inducing Treg expansion, CD25 upregulation, and inhibiting lupus nephritis based on the levels of proteinuria, autoantibody titers, and kidney histology scores. mIL-2/CD25 was effective even when treatment was initiated at the time when NZB × NZW mice already showed signs of advanced disease. Furthermore, we show coadministration of prednisolone, which SLE patients commonly take, did not interfere with the ability of mIL-2/CD25 to expand Tregs. The prednisolone and mIL-2/CD25 combination treatment results in improvements in most of the efficacy readouts relative to either monotherapy alone. Taken together, our results support further evaluation of IL-2/CD25 in the clinic for treating immune-mediated diseases such as SLE.


Subject(s)
Lupus Erythematosus, Systemic , T-Lymphocytes, Regulatory , Animals , CD8-Positive T-Lymphocytes , Forkhead Transcription Factors , Humans , Interleukin-2 , Interleukin-2 Receptor alpha Subunit , Lupus Erythematosus, Systemic/drug therapy , Mice , Mice, Inbred MRL lpr , Mice, Inbred NOD
16.
BMC Musculoskelet Disord ; 24(1): 839, 2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37880624

ABSTRACT

BACKGROUND: People with nonspecific low back pain (NSLBP) can also experience overlapping symptoms of lumbar spinal stenosis (LSS), but the impact on treatment outcomes is unknown. This study investigated differences in treatment outcomes for disability, back pain intensity, and leg pain intensity following an education and exercise therapy program for NSLBP patients with and without comorbid LSS symptoms. METHODS: This was a longitudinal analysis of 655 Danish participants in the GLA:D® Back program; an education and exercise therapy program for people with persistent NSLBP. Participants were classified as having comorbid LSS symptoms based on self-report. Linear mixed models were used to assess differences in change in disability (Oswestry Disability Index [0-100]) and back and leg pain intensity (Numeric Rating Scale [0-10]) at 3-, 6-, and 12-months between those with and without LSS symptoms. RESULTS: 28% of participants reported LSS symptoms. No certain differences in change in disability or back pain intensity improvement were observed at any time-point between those with and without LSS symptoms. Participants with LSS symptoms had slightly greater improvement in leg pain intensity at 6- (-0.7, 95% CI -1.2 to -0.2) and 12-months (-0.6, 95% CI -1.2 to -0.1). CONCLUSION: Compared to those without LSS symptoms, patients with persistent NSLBP and LSS symptoms can expect similar improvements in disability and back pain intensity, and slightly greater improvements in leg pain intensity with treatment. Therefore, education and exercise therapy programs designed for NSLBP are likely helpful for those also experiencing LSS symptoms.


Subject(s)
Low Back Pain , Spinal Stenosis , Humans , Spinal Stenosis/complications , Spinal Stenosis/therapy , Spinal Stenosis/diagnosis , Low Back Pain/diagnosis , Low Back Pain/therapy , Lumbar Vertebrae , Back Pain , Exercise Therapy , Patient Reported Outcome Measures
17.
BMC Musculoskelet Disord ; 24(1): 250, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-37005607

ABSTRACT

BACKGROUND: Previous studies have found that lumbar spinal stenosis (LSS) often co-occurs with knee or hip OA and can impact treatment response. However, it is unclear what participant characteristics may be helpful in identifying individuals with these co-occurring conditions. The aim of this cross-sectional study was to explore characteristics associated with comorbid symptoms of lumbar spinal stenosis (LSS) in people with knee or hip osteoarthritis (OA) enrolled in a primary care education and exercise program. METHODS: Sociodemographic, clinical characteristics, health status measures, and a self-report questionnaire on the presence of LSS symptoms was collected at baseline from the Good Life with osteoArthritis in Denmark primary care program for knee and hip OA. Cross-sectional associations between characteristics and the presence of comorbid LSS symptoms were assessed separately in participants with primary complaint of knee and hip OA, using domain-specific logistic models and a logistic model including all characteristics. RESULTS: A total of 6,541 participants with a primary complaint of knee OA and 2,595 participants with a primary complaint of hip OA were included, of which 40% and 50% reported comorbid LSS symptoms, respectively. LSS symptoms were associated with similar characteristics in knee and hip OA. Sick leave was the only sociodemographic variable consistently associated with LSS symptoms. For clinical characteristics, back pain, longer symptom duration and bilateral or comorbid knee or hip symptoms were also consistently associated. Health status measures were not consistently related to LSS symptoms. CONCLUSION: Comorbid LSS symptoms in people with knee or hip OA undergoing a primary care treatment program of group-based education and exercise were common and associated with a similar set of characteristics. These characteristics may help to identify people with co-occurring LSS and knee or hip OA, which can be used to help guide clinical decision-making.


Subject(s)
Osteoarthritis, Hip , Osteoarthritis, Knee , Spinal Stenosis , Humans , Osteoarthritis, Hip/diagnosis , Osteoarthritis, Hip/epidemiology , Cross-Sectional Studies , Spinal Stenosis/diagnosis , Spinal Stenosis/epidemiology , Spinal Stenosis/therapy , Osteoarthritis, Knee/diagnosis , Osteoarthritis, Knee/epidemiology , Osteoarthritis, Knee/therapy , Denmark/epidemiology
18.
J Occup Rehabil ; 33(4): 661-672, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37991648

ABSTRACT

PURPOSE: Evaluate benefits and harms of needling therapies (NT) for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing NT compared with placebo/sham, usual care, or no intervention (comparing interventions where the attributable effect could be isolated). We conducted meta-analyses where indicated and graded the certainty of evidence. RESULTS: We screened 1831 citations and 109 full text RCTs, yeilding 37 RCTs. The certainty of evidence was low or very low across all included outcomes. There was little or no difference between NT and comparisons across most outcomes; there may be some benefits for certain outcomes. Compared with sham, NT improved health-related quality of life (HRQoL) (physical) (2 RCTs; SMD = 0.20, 95%CI 0.07; 0.32) at 6 months. Compared with no intervention, NT reduced pain at 2 weeks (21 RCTs; MD = - 1.21, 95%CI - 1.50; - 0.92) and 3 months (9 RCTs; MD = - 1.56, 95%CI - 2.80; - 0.95); and reduced functional limitations at 2 weeks (19 RCTs; SMD = - 1.39, 95%CI - 2.00; - 0.77) and 3 months (8 RCTs; SMD = - 0.57, 95%CI - 0.92; - 0.22). In older adults, NT reduced functional limitations at 2 weeks (SMD = - 1.10, 95%CI - 1.71; - 0.48) and 3 months (SMD = - 1.04, 95%CI - 1.66; - 0.43). Compared with usual care, NT reduced pain (MD = - 1.35, 95%CI - 1.86; - 0.84) and functional limitations (MD = - 2.55, 95%CI - 3.70; - 1.40) at 3 months. CONCLUSION: Based on low to very low certainty evidence, adults with CPLBP experienced some benefits in pain, functioning, or HRQoL with NT; however, evidence showed little to no differences for other outcomes.


Subject(s)
Low Back Pain , Aged , Humans , Low Back Pain/therapy , Quality of Life , Practice Guidelines as Topic , Randomized Controlled Trials as Topic
19.
J Occup Rehabil ; 33(4): 625-635, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37991651

ABSTRACT

PURPOSE: Evaluate benefits and harms of education/advice for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing education/advice compared with placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of education/advice could be isolated). We conducted meta-analyses and graded the certainty of evidence. RESULTS: We screened 2514 citations and 86 full text RCTs and included 15 RCTs. Most outcomes were assessed 3 to 6 months post-intervention. Compared with no intervention, education/advice improved pain (10 RCTs, MD = -1.1, 95% CI -1.63 to -0.56), function (10 RCTs, SMD = -0.51, 95% CI -0.89 to -0.12), physical health-related quality of life (HRQoL) (2 RCTs, MD = 24.27, 95% CI 12.93 to 35.61), fear avoidance (5 RCTs, SMD = -1.4, 95% CI -2.51 to -0.29), depression (1 RCT; MD = 2.10, 95% CI 1.05 to 3.15), and self-efficacy (1 RCT; MD = 4.4, 95% CI 2.77 to 6.03). Education/advice conferred less benefit than sham Kinesio taping for improving fear avoidance regarding physical activity (1 RCT, MD = 5.41, 95% CI 0.28 to 10.54). Compared with usual care, education/advice improved pain (1 RCT, MD = -2.10, 95% CI -3.13 to -1.07) and function (1 RCT, MD = -7.80, 95% CI -14.28 to -1.32). There was little or no difference between education/advice and comparisons for other outcomes. For all outcomes, the certainty of evidence was very low. CONCLUSION: Education/advice in adults with CPLBP was associated with improvements in pain, function, HRQoL, and psychological outcomes, but with very low certainty.


Subject(s)
Low Back Pain , Adult , Humans , Exercise , Low Back Pain/therapy , Quality of Life , Practice Guidelines as Topic , Randomized Controlled Trials as Topic
20.
J Prosthet Dent ; 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37953208

ABSTRACT

This article describes a novel technique that allows the planning and placing of dental implants with their long axis parallel to a path of insertion chosen for a prospective removable partial denture. The technique is straightforward, uses digital technologies efficiently, and enables prosthetically driven implant placement. It also optimizes the outcome when dental implants are used in association with removable partial dentures.

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