To investigate change in knee cartilage composition over 96 months in overweight and obese participants with constant weight compared to those with weight loss (WL), and to assess how different WL ...regimens are associated with these changes.
We studied right knees of 760 participants (age 62.6 ± 9.0y; 465 females) with a baseline body mass index (BMI) >25 kg/m2 from the Osteoarthritis Initiative with mild to moderate or with risk factors for knee osteoarthritis. Participants losing weight (>5% of baseline BMI over 72 months; N = 380) were compared to controls with stable weight (SW, N = 380). Participants losing weight were categorized based on WL method (diet and exercise, diet only, exercise only) and compared to those with stable weight. Magnetic resonance imaging (MRI) at 3T was performed at baseline, 48- and 96-months. The association of WL and WL method with change in cartilage composition, measured with T2 mapping, was analyzed using mixed random effects models.
Compared to SW, WL was associated with a significantly slower increase in global (averaged over all compartments) cartilage T2 (adjusted mean difference of change in T2 ms/year 95% CI between the groups: 0.24 0.20, 0.41 ms/year; P < 0.001) and global deep layer cartilage T2 0.35 0.20, 0.42 ms/year; P < 0.001), suggesting slower cartilage deterioration. Compared to the SW group, slower increases in global T2 were observed in the diet and diet and exercise groups, but not in the exercise only group (P = 0.042, P = 0.003 and P = 0.85, respectively).
Our results suggest that WL may slow knee cartilage degeneration over 96 months, and that these potential benefits may differ by method of WL.
To compare progression over 8 years in knee compositional cartilage degeneration and structural joint abnormalities in knees with different types of anterior cruciate ligament (ACL) abnormalities ...over 8 years.
Baseline MR images of the right knees of 1899 individuals of the Osteoarthritis Initiative (OAI) with no evidence of or mild to moderate radiographic osteoarthritis were assessed for nontraumatic ACL abnormalities. The knees of 91 individuals showed nontraumatic ACL abnormalities (age 60.6 ± 9.8 y, 46 females; mucoid degeneration (MD), N = 37; complete tear (CT), N = 22; partial tear (PT), N = 32) and were frequency-matched to 91 individuals with normal ACL. MRIs were assessed for knee joint abnormalities using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) and cartilage T2 mapping at baseline, 4- and 8-year follow-up.
Over 8 years, cartilage T2 values of the medial tibia showed a significantly greater increase in individuals with MD, PT or CT compared to those with normal ACL (adjusted rate of change/year 95% confidence interval, normal ACL: 0.06 0.01, 0.23, MD: 0.34 0.07, 0.73, PT, 0.21 0.02, 0.33, CT, 0.51 0.16, 0.78), indicating an association of ACL abnormalities and an increased progression rate of cartilage degeneration in subjects with and without knee joint degeneration. This effect was also seen in cartilage T2 values averaged over all compartments (normal ACL: 0.08 0.05, 0.20 vs abnormal ACL: 0.27 0.06, 0.56).
Over 8 years, higher progression rates of cartilage degeneration, especially in the medial tibia, were associated with ACL abnormalities compared to those with normal ACL, in subjects with and without knee joint abnormalities.
Summary Objective To evaluate the association of prevalent unilateral total hip arthroplasty (THA) with worsening of degenerative knee abnormalities and clinical outcomes in the ipsilateral and ...contralateral knee. Methods Both knees of 30 individuals in the Osteoarthritis Initiative (OAI) with unilateral THA ( n = 14 left, n = 16 right) at baseline were assessed at baseline and at 4-year follow-up for Whole-organ MR Imaging Scores (WORMS), cartilage T2 relaxation times (only available for right knees), Western Ontario and McMasters Universities Arthritis Index (WOMAC) scores and upper leg isometric strength. Right knees of 30 individuals without THA were analyzed as controls. Contralateral knees were compared to ipsilateral knees with paired t -tests and to control knees with multivariate regression analysis adjusting for covariates. Results In paired analyses, compared to ipsilateral knees, contralateral knees had higher WORMS total ( P = 0.008) and cartilage scores ( P = 0.007) at baseline. Over 4 years contralateral knees worsened more on WORMS total score ( P = 0.008). Cartilage T2 values were higher in knees contralateral to the THA (baseline, P = 0.02; follow-up, P < 0.001). Contralateral knees had greater declines in knee extension strength ( P = 0.04) and had a trend for greater worsening in WOMAC pain, stiffness, function and total scores ( P = 0.04–0.09). Similar results were found comparing contralateral knees with control knees in multivariate regression models. Conclusions Prevalent unilateral THA is associated with an greater progression of degenerative findings for the knee contralateral to THA.
Background
Lower urinary tract symptoms (LUTS) are associated with prevalent frailty and functional impairment, but longitudinal associations remain unexplored.
Objectives
To assess the association ...of change in phenotypic frailty with concurrent worsening LUTS severity among older men without clinically significant LUTS at baseline.
Design
Multicenter, prospective cohort study.
Setting
Population-based.
Participants
Participants included community-dwelling men age ≥65 years at enrollment in the Osteoporotic Fractures in Men study.
Measurements
Data were collected at 4 visits over 7 years. Phenotypic frailty score (range: 0–5) was defined at each visit using adapted Fried criterion and men were categorized at baseline as robust (0), pre-frail (
1
–
2
), or frail (
3
–
5
). Within-person change in frailty was calculated at each visit as the absolute difference in number of criteria met compared to baseline. LUTS severity was defined using the American Urologic Association Symptom Index (AUASI; range: 0–35) and men with AUASI ≥8 at baseline were excluded. Linear mixed effects models were adjusted for demographics, health-behaviors, and comorbidities to quantify the association between within-person change in frailty and AUASI.
Results
Among 3235 men included in analysis, 48% were robust, 45% were pre-frail, and 7% were frail. Whereas baseline frailty status was not associated with change in LUTS severity, within-person increases in frailty were associated with greater LUTS severity (quadratic P<0.001). Among robust men at baseline, mean predicted AUASI during follow-up was 4.2 (95% CI 3.9, 4.5) among those meeting 0 frailty criteria, 4.6 (95% CI 4.3, 4.9) among those meeting 1 criterion increasing nonlinearly to 11.2 (95% CI 9.8, 12.6) among those meeting 5 criteria.
Conclusions
Greater phenotypic frailty was associated with nonlinear increases in LUTS severity in older men over time, independent of age and comorbidities. Results suggest LUTS and frailty share an underlying mechanism that is not targeted by existing LUTS interventions.
A DNA lesion created by oxidative stress is 7,8-dihydro-8-oxo-guanine (8-oxoG). Because 8-oxoG can mispair with adenine during DNA synthesis, it is of interest to understand the efficiency and ...fidelity of 8-oxoG bypass by DNA polymerases. We quantify bypass parameters for two DNA polymerases implicated in 8-oxoG bypass, Pols δ and η. Yeast Pol δ and yeast Pol η both bypass 8-oxoG and misincorporate adenine during bypass. However, yeast Pol η is 10-fold more efficient than Pol δ, and following bypass Pol η switches to less processive synthesis, similar to that observed during bypass of a cis-syn thymine-thymine dimer. Moreover, yeast Pol η is at least 10-fold more accurate than yeast Pol δ during 8-oxoG bypass. These differences are maintained in the presence of the accessory proteins RFC, PCNA and RPA and are consistent with the established role of Pol η in suppressing ogg1-dependent mutagenesis in yeast. Surprisingly different results are obtained with human and mouse Pol η. Both mammalian enzymes bypass 8-oxoG efficiently, but they do so less processively, without a switch point and with much lower fidelity than yeast Pol η. The fact that yeast and mammalian Pol η have intrinsically different catalytic properties has potential biological implications.
There is considerable potential to decarbonise household energy consumption through the electrification of heating systems which can absorb excess renewable power and mitigate power network ...constraints through intelligent control. However, current standards discourage low carbon electricity sources through outdated assumptions; predicated upon a traditional electricity network which had higher emissions. Consequently, the implementation of product Energy labelling across Europe is biased against electric space and water heating systems in favour of gas. This paper examines the impact of this bias through a case study of the European Union's product labelling directive for domestic hot water systems. Laboratory testing of a market leading electric water tank and an A rated instantaneous gas boiler has demonstrated efficiencies of 87.4% and 72.9% respectively. In spite of this, the labelling directive assigns a C rating to the tank. This is due to a conversion coefficient (CC) within the directive's calculation based on an average electricity generation efficiency of 40% without a similar coefficient for gas. This paper advocates the removal of the CC factor from the directive to normalise the comparison, thus promoting a technology uniquely suited towards absorbing intermittent renewable energy sources with negligible costs.
•Current standards discourage low carbon electricity through outdated assumptions.•Bias due to the use of conversion coefficient (CC) for electricity generation.•Higher efficiency electric HWTs have a lower ranking than less efficient gas boiler.•HWT can help integrate more renewables at minimal incremental cost.•Recommendation of removal of CC to unlock the potential of HWT.
Freedom from rejection in pediatric heart transplant recipients is highly variable across centers. This study aimed to assess the center variation in methods used to diagnose rejection in the ...first-year post-transplant and determine the impact of this variation on patient outcomes.
The PHTS registry was queried for all rejection episodes in the first-year post-transplant (2010-2019). The primary method for rejection diagnosis was determined for each event as surveillance biopsy, echo diagnosis, or clinical. The percentage of first-year rejection events diagnosed by surveillance biopsy was used to approximate the surveillance strategy across centers. Methods of rejection diagnosis were described and patient outcomes were assessed based on surveillance biopsy utilization among centers.
A total of 3985 patients from 56 centers were included. Of this group, 873 (22%) developed rejection within the first-year post-transplant. Surveillance biopsy was the most common method of rejection diagnosis (71.7%), but practices were highly variable across centers. The majority (73.6%) of first rejection events occurred within 3-months of transplantation. Diagnosis modality in the first-year was not independently associated with freedom from rejection, freedom from rejection with hemodynamic compromise, or overall graft survival.
Rejection in the first-year after pediatric heart transplant occurs in 22% of patients and most commonly in the first 3 months post-transplant. Significant variation exists across centers in the methods used to diagnose rejection in pediatric heart transplant recipients, however, these variable strategies are not independently associated with freedom from rejection, rejection with hemodynamic compromise, or overall graft survival.
The clinical and MRI presentation differs between earlier- and later-onset pediatric multiple sclerosis (MS), whereas the effect of age on the CSF inflammatory profile is unknown and may contribute ...to delayed diagnosis.
To compare the CSF cellular and immunoglobulin G (IgG) profiles between earlier- and later-onset pediatric MS.
We queried the databases of 6 pediatric MS centers for earlier-onset (onset <11 years) and later-onset (> or = 11 and <18 years) patients with MS or clinically isolated syndrome who underwent CSF analysis within the first 3 months of presentation (observational study). We compared CSF white blood cell (WBC) differential count, IgG index, and IgG oligoclonal bands between age groups.
We identified 40 earlier-onset (mean age at onset = 7.2 +/- 2.7 years, 60% females) and 67 later-onset pediatric MS patients (15.1 +/- 1.7 years, 63% females). Although WBC count tended to be higher in earlier-onset patients (median = 9/mm(3) 0-343 vs 6 0-140, p = 0.15), they had a lower proportion of lymphocytes (70% 0-100 vs 93% 0-100 of WBCs, p = 0.0085; difference = +3% per 1-year increase of age, p = 0.0011) and higher proportion of neutrophils than later-onset patients (0.5% 0-75 vs 0% 0-50 of WBCs, p = 0.16; difference = -1% per 1-year increase of age, p = 0.033). In earlier-onset disease, fewer patients had an elevated IgG index than in the later-onset group (35% vs 68% of patients, p = 0.031).
Age modifies the CSF profile at pediatric multiple sclerosis (MS) onset, which may mislead the diagnosis. Our findings suggest an activation of the innate rather than the adaptive immune system in the earlier stages of MS or an immature immune response.
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