Psychometric properties of the EQ-5D-5L in patients with hip or knee osteoarthritis: reliability,validity and responsiveness

Purpose

To study the psychometric properties, including reliability, validity and responsiveness, of the Spanish EQ-5D-5L questionnaire for patients with hip or knee osteoarthritis (OA).

Methods

We included 758 patients with hip or knee OA who completed the EQ-5D-5L and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline, of whom 644 also did 6 months later. The EQ-5D-5L contains five questions from which a utility index is derived. The WOMAC covers three dimensions: pain, stiffness and physical function. Floor and ceiling effects were calculated. Reliability was assessed using Cronbach’s alpha. Convergent validity was tested using the Spearman correlation coefficient between EQ-5D-5L and WOMAC. We examined known-groups validity by comparing the EQ-5D-5L between subgroups defined by WOMAC scores using ANOVA or the Kruskal–Wallis test. Effect sizes were calculated to assess responsiveness, and minimal clinically important difference (MCID) was estimated.

Results

The EQ-5D-5L showed minimal floor and ceiling effects (<?3%). Cronbach’s alpha was 0.86. The EQ-5D-5L index was strongly correlated with WOMAC pain and function scores (??0.688 and ??0.782). Patients with higher WOMAC scores had significantly (p?<?0.0001) lower EQ-5D-5L index. The 20.19% had hip or knee replacement during the follow-up. Effect sizes were small among non-surgical patients, but >?0.80 among “improved” surgical patients, being the MCID for improvement 0.32 points.

Conclusions

The results support the reliability, validity and responsiveness of the EQ-5D-5L, overcoming the limitations of the EQ-5D-3L in these patients. Therefore, the EQ-5D-5L could be very useful as an outcome measure, at least in patients with hip or knee OA.

     

Development and characterization of poly(lactic-co-glycolic) acid nanoparticles loaded with copaiba oleoresin

Abstract

Copaiba oleoresin (CPO), obtained from Copaifera landgroffii, is described as active to a large number of diseases and more recently in the endometriosis treatment. In this work, poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing CPO were obtained using the design of experiments (DOE) as a tool to optimize the production process. The nanoparticles optimized by means of DOE presented an activity in relation to the cellular viability of endometrial cells. The DOE showed that higher amounts of CPO combined with higher surfactant concentrations resulted in better encapsulation efficiency and size distribution along with good stability after freeze drying. The encapsulation efficiency was over 80% for all produced nanoparticles, which also presented sizes below 300?nm and spherical shape. A decrease in viability of endometrial stromal cells from ectopic endometrium of patients with endometriosis and from eutopic endometriotic lesions was demonstrated after 48?h of incubation with the CPO nanoparticles. The nanoparticles without CPO were not able to alter the cell viability of the same cells, indicating that this material was not cytotoxic to the tested cells and suggesting that the effect was specific to CPO. The results indicate that the use of CPO nanoparticles may represent a promising alternative for the treatment of endometriosis.     

Mediterranean Diet and Cognitive Status in Free-Living Elderly: A Cross-Sectional Study in Northern Italy

Objective: Few data are available on the Italian elderly population with regard to adherence to the Mediterranean diet (MD) and cognitive impairment. Our aim was to investigate adherence to the MD and its association with cognitive function in an Italian urban sample.

Methods: A cross-sectional study of 279 participants aged ≥ 65 years (80 men, 199 women) was carried out at a nutritional center. Adherence to the MD was evaluated using a 14-item questionnaire. Cognitive function was assessed with the Mini-Mental State Examination (MMSE).

Results: The clinical and nutritional assessments performed revealed 30.1% to have a dietary pattern in accordance with the MD; 13.6% had suspected or mild cognitive impairment (MMSE score ≤ 23). The MD pattern was associated with a lower risk of cognitive impairment (odds ratio [OR] = 0.39; 95% confidence interval [CI], 0.15–0.99; p = 0.045), as was the consumption of wine (OR = 0.37; 95% CI, 0.16–0.84; p = 0.018) and nuts (OR = 0.30; 95% CI, 0.13–0.69, p = 0.005). No association was found with other food groups.

Conclusion: A closer adherence to the MD was associated with a better cognitive status. Further cohort studies and randomized controlled trials are warranted.     

The Uruguayan semen donor population: A twenty-eight-year retrospective study

Several studies have reported a global decline in seminal quality over the years. The objective of this study was to describe the semen donor population of Uruguay through comparing data of successive samples banked by the same donors and the analysis of their semen and physical characteristics, ancestry origin and educational level. A total of 3,449 ejaculated samples collected from 71 donors, cryobanked between 1989 and March 2017 at Fertilab, were analysed. Results revealed a mean age of 23.90 ± 3.98 years, an average weight of 74.95 ± 1.09 kg and a mean height of 1.78 ± 0.06 m. The majority of the donors trace their origin to Europe (74.65%, 53/71) and 66.19% (47/71) have a level of education higher than secondary school. We observed longitudinal differences in two parameters, that is sperm concentration and semen volume. Sperm concentration declined, while semen volume increased significantly over the 28-year period. The results of the present study are in accordance with that of previous articles that also reported a decline in sperm concentration over time. However, no differences were observed in total sperm number per ejaculate due to the increase in semen volume values, thus reflecting no real changes in sperm production over time.     

Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) for primary surgical prevention of breast cancer‐related lymphedema: Over 4 years follow‐up

Breast cancer‐related lymphedema (LE) represents an important morbidity that jeopardizes breast cancer patients' quality of life. Different attempts to prevent LE brought about improvements in the incidence of the pathology but LE still represents a frequent occurrence in breast cancer survivors. Over 4 years ago, Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) was proposed and long‐term results are reported in this study. From July 2008 to December 2012, 74 patients underwent axillary nodal dissection for breast cancer treatment together with LYMPHA procedure. Volumetry was performed preoperatively in all patients and after 1, 3, 6, 12 months, and once a year. Lymphoscintigraphy was performed in 45 patients preoperatively and in 30 also postoperatively after at least over 1 year. Seventy one patients had no sign of LE, and volumetry was coincident to preoperative condition. In three patients, LE occurred after 8–12 months postoperatively. Lymphoscintigraphy showed the patency of lymphatic‐venous anastomoses at 1–4 years after operation. LYMPHA technique represents a successful surgical procedure for primary prevention of arm LE in breast cancer patients. © 2014 Wiley Periodicals, Inc. Microsurgery 34:421–424, 2014.     

Formation and Investigation of Physicochemical,Biological and Bacteriostatic Properties of Nanocomposite Foils Containing Silver Nanoparticles and Graphene Oxide in Hyaluronic Acid Matrix

Natural polysaccharides, including hyaluronic acid, find a wide range of applications in biomedical sciences. There is a growing interest in nanocomposites containing hyaluronic acid and nanoparticles such as nanometals or graphene. In this study, we prepared foils of pure sodium hyaluronate and sodium hyaluronate containing nanosilver, graphene oxide, nanosilver/graphene oxide and characterized their properties. UV-vis spectroscopy and scanning electron microscopy (SEM) confirmed the formation of 10–20 nm silver nanoparticles. The structural changes were investigated using Fourier transforms infrared (FTIR) spectra and size exclusion chromatography. The obtained results suggest changes in molecular weights in the samples containing nanoparticles, which was highest in a sample containing nanosilver/graphene oxide. We also assessed the mechanical properties of the foils (thickness, tensile strength and elongation at break) and their wettability. The foils containing nanosilver and nanosilver/graphene oxide presented bacteriostatic activity against E. coli, Staphylococcus spp. and Bacillus spp., which was not observed in the control and sample containing graphene oxide. The composites containing graphene oxide and nanosilver/graphene oxide exhibited a cytotoxic effect on human melanoma WM266-4 cell lines (ATCC, Manassas, VA, USA).     

Identification of Nucleoside Analogs as Inducers of Neuronal Differentiation in a Human Reporter Cell Line and Adult Stem Cells

Nucleoside analogs (NSAs) were among the first chemotherapeutic agents and could also be useful for the manipulation of cell fate. To investigate the potential of NSAs for the induction of neuronal differentiation, we developed a novel phenotypic assay based on a human neuron‐committed teratocarcinoma cell line (NT2) as a model for neuronal progenitors and constructed a NT2‐based reporter cell line that expressed eGFP under the control of a neuron‐specific promoter. We tested 38 structurally related NSAs and determined their activity to induce neuronal differentiation by immunocytochemistry of neuronal marker proteins, live cell imaging, fluorometric detection and immunoblot analysis. We identified twelve NSAs, which induced neuronal differentiation to different extents. NSAs with highest activity carried a halogen substituent at their pyrimidine nucleobase and an unmodified or 2′‐O‐methyl substituted 2‐deoxy‐β‐D‐ribofuranosyl residue as glyconic moiety. Cladribine, a purine nucleoside with similar structural features and in use to treat leukemia and multiple sclerosis, induced also differentiation of adult human neural crest‐derived stem cells. Our results suggest that NSAs could be useful for the manipulation of neuronal cell fate in cell replacement therapy or treatment of neurodegenerative disorders. The data on the structure and function relationship will help to design compounds with increased activity and low toxicity.     

Expression of serum vascular endothelial growth factor correlates with clinical outcome in multiple myeloma

A total of 34 multiple myeloma (MM) patients (17 recently diagnosed and 17 in progression of the disease) treated at the Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation Medical University in Wroc?aw were studied. Among the 19 females and 15 males, aged 31-72 years, there were 17 IgG, 9 IgA and 1 IgM, one with plasma cell leukaemia and 6 with light chain disease. Staging according to Durie and Salmon disclosed: 7--IIA stage, 15--IIIA and 12--IIIB. Blood hyperviscosity symptoms (HS) developed in 9 patients, and precomatic state or coma was observed in four of them. Control group was constituted of 14 healthy subjects--10 women and 4 men aged 32-51 years. Vascular endothelial growth factor (VEGF) serum concentration in MM patients varied from 0 pg/ml to 760 pg/ml, mean 148.75 pg/ml, SD = 204.4 and in controls 0 pg/ml--164 pg/ml, mean 31.5, SD = 23.3; p < 0.05. The mean VEGF level in recently diagnosed patients was higher than in progression of the disease, mean 188.6 pg/ml, SD = 230.6 and mean 110.9 pg/ml, SD = 177.9; respectively, but the difference was not statistically significant. The patients with stage III had significantly (p < 0.05) higher VEGF level than those in stage II (mean 303.1 pg/ml, SD = 302.2 and mean 89.0 pg/ml SD = 121.6) respectively. The group of MM patients with renal failure (creatinine level > 2 mg%) had higher VEGF level than those with normal renal function: mean 199.9 pg/ml, SD = 235, and mean 46.9 SD = 47 respectively, p < 0.01. Elevated VEGF level was also present in comatic and precomatic patients when compared with hyperviscosity patients without these symptoms (p < 0.05). In multiple myeloma patients no correlation was found between the serum VEGF level and percentage of bone marrow plasma cells, serum beta-2-m and monoclonal Ig levels, levels of Hb, albumine and LDH. Median survival time (M-ST) of patients with VEGF higher than 71, 0 pg/ml was 32 months, M-ST of patients with VEGF below 71 pg/ml was 52 months. In summary: serum level of VEGF in advanced state of multiple myeloma was elevated and correlated with clinical state. An elevated serum level of VEGF is associated with a poor prognosis.     

The quest for improved air quality may push China to continue its CO2 reduction beyond the Paris Commitment

China is challenged with the simultaneous goals of improving air quality and mitigating climate change. The “Beautiful China” strategy, launched by the Chinese government in 2020, requires that all cities in China attain 35 μg/m³ or below for annual mean concentration of PM_2.5 (particulate matter with aerodynamic diameter less than 2.5 μm) by 2035. Meanwhile, China adopts a portfolio of low-carbon policies to meet its Nationally Determined Contribution (NDC) pledged in the Paris Agreement. Previous studies demonstrated the cobenefits to air pollution reduction from implementing low-carbon energy policies. Pathways for China to achieve dual targets of both air quality and CO₂ mitigation, however, have not been comprehensively explored. Here, we couple an integrated assessment model and an air quality model to evaluate air quality in China through 2035 under the NDC scenario and an alternative scenario (Co-Benefit Energy [CBE]) with enhanced low-carbon policies. Results indicate that some Chinese cities cannot meet the PM_2.5 target under the NDC scenario by 2035, even with the strictest end-of-pipe controls. Achieving the air quality target would require further reduction in emissions of multiple air pollutants by 6 to 32%, driving additional 22% reduction in CO₂ emissions relative to the NDC scenario. Results show that the incremental health benefit from improved air quality of CBE exceeds 8 times the additional costs of CO₂ mitigation, attributed particularly to the cost-effective reduction in household PM_2.5 exposure. The additional low-carbon energy polices required for China’s air quality targets would lay an important foundation for its deep decarbonization aligned with the 2 °C global temperature target.

China is facing serious air pollution problems, particularly for ambient PM_2.5 (particulate matter with aerodynamic diameter less than 2.5 μm) which has harmful effects on human health (1–3). To protect human health, strengthened air pollution control policies were recently implemented in China targeting 35 μg⋅m⁻³ or less for all cities by 2035 (4). The Action Plan on Prevention and Control of Air Pollution, released in 2013, has resulted in noticeable reductions in urban ambient PM_2.5 concentrations (5, 6). In 2018, however, China’s national PM_2.5 standard of 35 μg⋅m⁻³ annual average was exceeded in 217 of China’s 338 cities at the prefecture or higher level, not to mention exceedance of the World Health Organization (WHO) guideline (annual mean PM_2.5 concentration <10 μg⋅m⁻³). A big challenge for future improvement is that advanced end-of-pipe control technologies have already been widely applied in electric and industrial sectors (7, 8). For example, over 90% of coal-fired power plants had installed end-of-pipe control technologies by 2018 (8). Therefore, the potential for further reductions using end-of-pipe control measures might be limited, and implementation of low-carbon energy policies to constrain total energy consumption and promote a transition to clean energy is expected to be an inevitable option for further reducing air pollution (9).The impacts of climate change on humans and ecosystems have also received considerable attention in China over the past few decades, and strategies for mitigating these impacts have been adopted (10). In 2016, China officially signed its Nationally Determined Contribution (NDC) in the Paris Commitment, which pledges for CO₂ emissions per unit of GDP in 2030 to fall by 60 to 65% compared to 2005. A big concern arises as to whether China will continue its carbon reduction even under a pessimistic international situation after the US withdrawal from the Paris Agreement in 2019. Previous studies (11–18) have suggested that climate mitigation-oriented low-carbon energy policies can result in a reduction in air pollution.Therefore, there is a question as to whether China needs the application of low-carbon energy technologies and fuels to meet its air quality target. Such synergy is important, since many developing countries (e.g., China, India) are currently experiencing serious air pollution problems, and reducing air pollution is typically a more pressing national concern than climate mitigation (19). This could lead to continuous reductions in CO₂ emissions even under a pessimistic international situation for mitigating climate change.Here, we project future air quality attainment in China through 2035, assess the CO₂ reduction cobenefits associated with attaining the ambient PM_2.5 standards, and evaluate the health and climate impacts associated with air quality attainment-oriented energy policies. We accomplish this by coupling an integrated assessment model [GCAM, the Global Climate Assessment Model (20)], tuned with a detailed bottom-up emission inventory (21), and an air quality model [CMAQ, the Community Multiscale Air Quality model (22)] to evaluate future air quality and CO₂ emissions, and an integrated exposure−response (IER) model to evaluate the health effects due to the long-term ambient O₃ and both ambient and household PM_2.5 exposures in China. This integrated approach captures the nonlinearities among energy, emissions, concentrations, and health, thus allowing us to assess the cobenefits of air quality attainment on protecting health and mitigating CO₂ in an internally consistent framework.This study investigates future emissions of air pollutants and CO₂ in China under three future pathways with different considerations of two energy scenarios and two end-of-pipe control levels (Table 1). We first designed the NDC−current legislation (CLE) pathway to represent the CO₂ intensity reduction targets outlined by China’s NDC to meet the Paris Commitment (23), with CLE level of end-of-pipe controls. This pathway represents the current ongoing energy policies and end-of-pipe control measures to be conducted in China following CLE. For the purpose of air quality attainment, we first designed the NDC−maximum feasible reduction (MFR) pathway to represent the same ongoing energy policies as the NDC−CLE scenario, but with MFR level realized by end-of-pipe controls. Additionally, to achieve the air quality attainment in 2035, we also introduce the CBE−MFR pathway, in which low-carbon energy policies beyond the NDC requirements are implemented (i.e., the cobenefit energy scenario [CBE]) with the MFR level of end-of-pipe controls.Table 1.Design of future projection of air pollutant and CO₂ emissions

Persistence of a Repressed Epstein-Barr Virus Genome in Burkitt Lymphoma Cells Made Resistant to 5-Bromodeoxyuridine

The P3HR-1 line of human lymphoblastoid cells that is Epstein-Barr virus positive was made resistant to 5-bromodeoxyuridine. Epstein-Barr virus-associated antigens, but not virus particles, were produced in P3HR-1(BU) cells maintained on 5-bromodeoxyuridine. However, virus particles did appear within 4 days after removal of the drug. Thymidine kinase activity was limited to P3HR-1(BU) cells producing viral antigen, whereas all control P3HR-1 cells showed thymidine kinase activity regardless of viral antigen synthesis.Cellular DNA in most P3HR-1(BU) cells was made via pathways that did not involve thymidine kinase. In cells having a pathway that involved thymidine kinase, a second DNA of density 1.71 g/cm(3), corresponding to Epstein-Barr virus, was detected.IT WAS CONCLUDED THAT: (a) a repressed Epstein-Barr virus genome persists in P3HR-1(BU) cells that do not contain thymidine kinase, with activation of the viral genome being accompanied by productive infection and the appearance of enzyme, and (b) thymidine kinase activity in P3HR-1(BU) cells could be used as a marker for viral genome expression.