Exploring Multifunctional Response of Ca10(PO4)6(OH)2-K0.5Na0.5NbO3 Ceramic Composite for Biomedical Applications.

This study focuses on investigating the intriguing properties of Ca10(PO4)6(OH)2 (HAP)-K0.5Na0.5NbO3 (KNN) bioceramic composites, seeking to elucidate the relationship between their structural, electrical, biological, and optical behavior. The article begins with a close inspection of the O 1s spectra of the specimens obtained from X-ray photoelectron spectroscopy (XPS). The spectra reveal the peak related to lattice oxygen, O vacancy and the surface adsorbed O. The formed O vacancy strongly influences the changes in lattice parameters as observed from the X-ray diffraction (XRD) patterns. The frequency variation of the dielectric response for the composites in the radio frequency (RF) regime has electrical polarization effective for biomedical applications. Nyquist plots along with equivalent RC circuits further confirm that those electrical responses are mainly contributed from the grain boundaries. Adsorption dynamics of protein on the ceramic surface are investigated using bovine serum albumin (BSA), which established the major role of electrostatic interaction. Surface charge and O vacancies are modeled to understand the adsorption of protein and a linear correlation is reported. The role of O vacancies in modulating adsorption dynamics adds a new dimension to this study. The conformational change of BSA has also been considered by constructing the secondary structure following the protein-ceramic interaction. Excitingly, the composites are also found to be fluorescent active, a courtesy of the defects and vacancies leading to electron-hole recombination in the forbidden region. These promising properties envision an exciting future for HAP-KNN composites, especially in the domain of bioimaging and bone-tissue engineering.

Which risk factors determine cartilage thickness and composition change in radiographically normal knees? - Data from the Osteoarthritis Initiative.

Objective: Therapy for osteoarthritis ideally aims at preserving structure before radiographic change occurs. This study tests: a) whether longitudinal deterioration in cartilage thickness and composition (transverse relaxation-time T2) are greater in radiographically normal knees "at risk" of incident osteoarthritis than in those without risk factors; and b) which risk factors may be associated with these deteriorations. Design: 755 knees from the Osteoarthritis Initiative were studied; all were bilaterally Kellgren Lawrence grade [KLG] 0 initially, and had magnetic resonance images available at 12- and 48-month follow-up. 678 knees were "at risk", whereas 77 were not (i.e., non-exposed reference). Cartilage thickness and composition change was determined in 16 femorotibial subregions, with deep and superficial T2 being analyzed in a subset (n â€‹= â€‹59/52). Subregion values were used to compute location-independent change scores. Results: In KLG0 knees "at risk", the femorotibial cartilage thinning score (-634 â€‹± â€‹516 â€‹µm) over 3 years exceeded the thickening score by approximately 20%, and was 27% greater (p â€‹< â€‹0.01; Cohen D -0.27) than the thinning score in "non-exposed" knees (-501 â€‹± â€‹319 â€‹µm). Superficial and deep cartilage T2 change, however, did not differ significantly between both groups (p â€‹≥ â€‹0.38). Age, sex, body mass index, knee trauma/surgery history, family history of joint replacement, presence of Heberden's nodes, repetitive knee bending were not significantly associated with cartilage thinning (r2<1%), with only knee pain reaching statistical significance. Conclusions: Knees "at risk" of incident knee OA displayed greater cartilage thinning scores than those "non-exposed". Except for knee pain, the greater cartilage loss was not significantly associated with demographic or clinical risk factors.

Assessment of groundwater salinity using principal component analysis (PCA): a case study from Mewat (Nuh), Haryana, India.

In the present study, principal component analysis (PCA) is used to investigate the processes controlling groundwater salinity in the Mewat (Nuh) district, Haryana, India. Twenty groundwater samples were collected from salinity-affected areas in the March-April months of years 2018 and 2019 and were analyzed for chemical variables pH, EC, Ca2+, Mg2+, Na+, K+, [Formula: see text], Cl-, SO42-, [Formula: see text], TDS, and total hardness. Three principal components were selected based on the eigen value, which explains 79.58% and 85.08% of the total variation in the years 2018 and 2019, respectively. The first principal component (PC-1) is identified with salinity, the second principal component (PC-2) with alkalinity, and the third principal component (PC-3) described the pollution. When the yearly comparison was made, the samples collected in 2019 were found to have an increased salinity compared to 2018, which shows an increased vulnerability to the aquifer of Mewat on account of the decline in rainfall recharge. It was also evident that declining recharge also triggered the recharge from other sources; thus, the impact of pollution is more pronounced in 2019 compared to 2018.

Performance and Stability of Pearl Millet Varieties for Grain Yield and Micronutrients in Arid and Semi-Arid Regions of India.

Pearl millet [Pennisetum glaucum (L.) R. Br.] is grown under both arid and semi-arid conditions in India, where other cereals are hard to grow. Pearl millet cultivars, hybrids, and OPVs (open pollinated varieties) are tested and released by the All India Coordinated Research Project on Pearl Millet (AICRP-PM) across three zones (A1, A, and B) that are classified based on rainfall pattern. Except in locations with extreme weather conditions, hybrids dominate pearl millet growing areas, which can be attributed to hybrid vigor and the active role of the private sector. The importance of OPVs cannot be ruled out, owing to wider adaptation, lower input cost, and timely seed availability to subsidiary farmers cultivating this crop. This study was conducted to scrutinize the presently used test locations for evaluation of pearl millet OPVs across India, identify the best OPVs across locations, and determine the variation in grain Fe and Zn contents across locations in these regions. Six varieties were evaluated across 20 locations in A1 and A (pooled as A) and B zones along with three common checks and additional three zonal adapted checks in the respective zones during the 2019 rainy season. Recorded data on yield and quality traits were analyzed using genotype main effects and genotype × environment interaction biplot method. The genotype × environment (G × E) interaction was found to be highly significant for all the grain yield and agronomic traits and for both micronutrients (iron and zinc). However, genotypic effect (G) was four (productive tillers) to 49 (grain Fe content) times that of G × E interaction effect for various traits across zones that show the flexibility of OPVs. Ananthapuramu is the ideal test site for selecting pearl millet cultivars effectively for adaptation across India, while Ananthapuramu, Perumallapalle, and Gurugram can also be used as initial testing locations. OPVs MP 599 and MP 600 are identified as ideal genotypes, because they showed higher grain and fodder yields and stability compared with other cultivars. Iron and zinc concentration showed highly significant positive correlation (across environment = 0.83; p < 0.01), indicating possibility of simultaneous effective selection for both traits. Three common checks were found to be significantly low yielders than the test entries or zonal checks in individual zones and across India, indicating the potential of genetic improvement through OPVs.

Deciphering Genotype-By-Environment Interaction for Target Environmental Delineation and Identification of Stable Resistant Sources Against Foliar Blast Disease of Pearl Millet.

Once thought to be a minor disease, foliar blast disease of pearl millet, caused by Magnaporthe grisea, has recently emerged as an important biotic constraint for pearl millet production in India. The presence of a wider host range as well as high pathogenic heterogeneity complicates host-pathogen dynamics. Furthermore, environmental factors play a significant role in exacerbating the disease severity. An attempt was made to unravel the genotype-by-environment interactions for identification and validation of stable resistant genotypes against foliar blast disease through multi-environment testing. A diversity panel consisting of 250 accessions collected from over 20 different countries was screened under natural epiphytotic conditions in five environments. A total of 43 resistant genotypes were found to have high and stable resistance. Interestingly, most of the resistant lines were late maturing. Combined ANOVA of these 250 genotypes exhibited significant genotype-by-environment interaction and indicated the involvement of crossover interaction with a consistent genotypic response. This justifies the necessity of multi-year and multi-location testing. The first two principal components (PCs) accounted for 44.85 and 29.22% of the total variance in the environment-centered blast scoring results. Heritability-adjusted genotype plus genotype × environment interaction (HA-GGE) biplot aptly identified "IP 11353" and "IP 22423, IP 7910 and IP 7941" as "ideal" and "desirable" genotypes, respectively, having stable resistance and genetic buffering capacity against this disease. Bootstrapping at a 95% confidence interval validated the recommendations of genotypes. Therefore, these genotypes can be used in future resistance breeding programs in pearl millet. Mega-environment delineation and desirability index suggested Jaipur as the ideal environment for precise testing of material against the disease and will increase proper resource optimization in future breeding programs. Information obtained in current study will be further used for genome-wide association mapping of foliar blast disease in pearl millet.

An enhanced T-wave delineation method using phasor transform in the electrocardiogram.

Accurate detection of key components plays a vital role in determining cardiovascular diseases in the ECG. In this method, we propose an enhanced T-wave delineation method using the phasor transform. Discrete Wavelet Transform (DWT) and median filters were used to suppress the high-frequency noise and baseline drift during pre-processing. The phasor transform was used to detect and locate the delineation points before and after the T-wave. The proposed method was tested on the QTDB for R-peak, T-peak, and Toffdetection. It achieved both sensitivity (Se%) and positive predictivity (+P%) values of 100 for R-peak detection. In T-peak detection, method shows Se % = 99.46 and +P % = 99.54, respectively. This method has reported Se% = 99.34 and +P% = 99.48 for Toffdetection in the ECG. The achieved results show that the method can be used for cardiac arrhythmia detection related to the morphology of T-wave.

Population genetic screening efficiently identifies carriers of autosomal dominant diseases.

Three inherited autosomal dominant conditions-BRCA-related hereditary breast and ovarian cancer (HBOC), Lynch syndrome (LS) and familial hypercholesterolemia (FH)-have been termed the Centers for Disease Control and Prevention Tier 1 (CDCT1) genetic conditions, for which early identification and intervention have a meaningful potential for clinical actionability and a positive impact on public health1. In typical medical practice, genetic testing for these conditions is based on personal or family history, ethnic background or other demographic characteristics2. In this study of a cohort of 26,906 participants in the Healthy Nevada Project (HNP), we first evaluated whether population screening could efficiently identify carriers of these genetic conditions and, second, we evaluated the impact of genetic risk on health outcomes for these participants. We found a 1.33% combined carrier rate for pathogenic and likely pathogenic (P/LP) genetic variants for HBOC, LS and FH. Of these carriers, 21.9% of participants had clinically relevant disease, among whom 70% had been diagnosed with relevant disease before age 65. Moreover, 90% of the risk carriers had not been previously identified, and less than 19.8% of these had documentation in their medical records of inherited genetic disease risk, including family history. In a direct follow-up survey with all carriers, only 25.2% of individuals reported a family history of relevant disease. Our experience with the HNP suggests that genetic screening in patients could identify at-risk carriers, who would not be otherwise identified in routine care.

Examining Timeliness of Total Knee Replacement Among Patients with Knee Osteoarthritis in the U.S.: Results from the OAI and MOST Longitudinal Cohorts.

BACKGROUND: Patients with knee osteoarthritis may undergo total knee replacement too early or may delay or underuse this procedure. We quantified these categories of total knee replacement utilization in 2 cohorts of participants with knee osteoarthritis and investigated factors associated with each category. METHODS: Data were pooled from 2 multicenter cohort studies that collected demographic, patient-reported, radiographic, clinical examination, and total knee replacement utilization information longitudinally on 8,002 participants who had or were at risk for knee osteoarthritis and were followed for up to 8 years. Validated total knee replacement appropriateness criteria were longitudinally applied to classify participants as either potentially appropriate or likely inappropriate for total knee replacement. Participants were further classified on the basis of total knee replacement utilization into 3 categories: timely (indicating that the patient had total knee replacement within 2 years after the procedure had become potentially appropriate), potentially appropriate but knee not replaced (indicating that the knee had remained unreplaced for >2 years after the procedure had become potentially appropriate), and premature (indicating that the procedure was likely inappropriate but had been performed). Utilization rates were calculated, and factors associated with each category were identified. RESULTS: Among 8,002 participants, 3,417 knees fulfilled our inclusion and exclusion criteria and were classified into 1 of 3 utilization categories as follows: 290 knees (8% of the total and 9% of the knees for which replacement was potentially appropriate) were classified as "timely", 2,833 knees (83% of the total and 91% of those for which replacement was potentially appropriate) were classified as "potentially appropriate but not replaced", and 294 knees (comprising 9% of the total and 26% of the 1,114 total knee replacements performed) were considered to be "likely inappropriate" yet underwent total knee replacement and were classified as "premature". Of the knees that were potentially appropriate but were not replaced, 1,204 (42.5%) had severe symptoms. Compared with the patients who underwent timely total knee replacement, the likelihood of being classified as potentially appropriate but not undergoing total knee replacement was greater for black participants and the likelihood of having premature total knee replacement was lower among participants with a body mass index of >25 kg/m and those with depression. CONCLUSIONS: In 2 multicenter cohorts of patients with knee osteoarthritis, we observed substantial numbers of patients who had premature total knee replacement as well as of patients for whom total knee replacement was potentially appropriate but had not been performed >2 years after it had become potentially appropriate. Further understanding of these observations is needed, especially among the latter group. CLINICAL RELEVANCE: Undergoing total knee replacement too early may result in little or no benefit while exposing the patient to the risks of a major operation, whereas waiting too long may cause limitations in physical activity that in turn increase the risk of additional disability and chronic disease; however, little is known about timing of this surgery. We quantified the extent of premature, timely, and delayed use, and found a high prevalence of both premature and delayed use.

Identification of heterotic groups in South-Asian-bred hybrid parents of pearl millet.

KEY MESSAGE: Pearl millet breeding programs can use this heterotic group information on seed and restorer parents to generate new series of pearl millet hybrids having higher yields than the existing hybrids. Five hundred and eighty hybrid parents, 320 R- and 260 B-lines, derived from 6 pearl millet breeding programs in India, genotyped following RAD-GBS (about 0.9 million SNPs) clustered into 12 R- and 7 B-line groups. With few exceptions, hybrid parents of all the breeding programs were found distributed across all the marker-based groups suggesting good diversity in these programs. Three hundred and twenty hybrids generated using 37 (22 R and 15 B) representative parents, evaluated for grain yield at four locations in India, showed significant differences in yield, heterosis, and combining ability. Across all the hybrids, mean mid- and better-parent heterosis for grain yield was 84.0% and 60.5%, respectively. Groups G12 B × G12 R and G10 B × G12 R had highest heterosis of about 10% over best check hybrid Pioneer 86M86. The parents involved in heterotic hybrids were mainly from the groups G4R, G10B, G12B, G12R, and G13B. Based on the heterotic performance and combining ability of groups, 2 B-line (HGB-1 and HGB-2) and 2 R-line (HGR-1 and HGR-2) heterotic groups were identified. Hybrids from HGB-1 × HGR-1 and HGB-2 × HGR-1 showed grain yield heterosis of 10.6 and 9.3%, respectively, over best hybrid check. Results indicated that parental groups can be formed first by molecular markers, which may not predict the best hybrid combination, but it can reveal a practical value of assigning existing and new hybrid pearl millet parental lines into heterotic groups to develop high-yielding hybrids from the different heterotic groups.

Enhancement of the heart sound envelope using the logistic function amplitude moderation method.

This paper presents a new method to extract the envelope of the fundamental heart sound (S1 and S2) using the logistic function. The sigmoid characteristic of the logistic function is incorporated to segregate S1, and S2 signal intensities from silent or noise interfered systolic and diastolic intervals in a heart sound cycle. This signal intensity transformation brings uniformity to the envelope peak of S1 and S2 sound by inclining the transform intensity distribution towards the upper asymptote of the sigmoid curve. The proposed logistic function based amplitude moderation (LFAM) envelogram method involves finding the critical upper amplitude (xuc) above which the signals will be categorized as loud sound and the critical lower amplitude (xlc) below which the signal will be considered as noise. These critical values are regressively obtained from the signal itself by histogram analysis of intensity distribution. The performance is evaluated on noisy PCG dataset taken from PhysioNet/Computing in Cardiology Challenge 2016. The LFAM envelope yields better hill-valley discrimination of heart sounds from its silent/noisy signal intervals. The enhance heart sound envelope peaks are better than conventional methods. The proposed envelope feature is evaluated for heart sound segmentation using HSMM. There is a significant improvement in segmentation accuracy, especially at a low signal-to-noise ratio. The best average F1 score is 97.73%.

Voltage-gated proton channels exist in the plasma membrane of human oocytes.

STUDY QUESTION: Do human oocytes express voltage-gated proton channels? SUMMARY ANSWER: Human oocytes exhibit voltage-gated proton currents. WHAT IS KNOWN ALREADY: Voltage-gated proton currents have been reported in human sperm, where they contribute to capacitation and motility. No such studies of human oocytes exist. STUDY DESIGN, SIZE, DURATION: Voltage-clamp studies were undertaken using entire oocytes and vesicles derived from oocytes and in excised patches of membrane from oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Frozen, thawed human metaphase II oocytes were obtained from material donated to the gamete repository at the Rush Center for Advanced Reproductive Care. Prior to patch clamping, oocytes were warmed and equilibrated. Formation of an electrically tight seal requires exposing bare oolemma. Sections of the zona pellucida (ZP) were removed using a laser, followed by repeated pipetting, to further separate the oocyte from the ZP. Patch-clamp studies were performed using the whole-cell configuration on oocytes or vesicles derived from oocytes, and using inside-out patches of membrane, under conditions optimized to detect voltage-gated proton currents. MAIN RESULTS AND THE ROLE OF CHANCE: Proton currents are present at significant levels in human oocytes where they exhibit properties similar to those reported in other human cells, as well as those in heterologous expression systems transfected with the HVCN1 gene that codes for the voltage-gated proton channel. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Human oocytes are large cells, which limits our ability to control the intracellular solution. Subtle effects of cryopreservation by vitrification and subsequent warming on properties of HVCN1, the HVCN1 gene product, cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS: Possible functions for voltage-gated proton channels in human oocytes may now be contemplated. STUDY FUNDING/COMPETING INTEREST(S): NIH R35GM126902 (TED), Bears Care (DM). No competing interests. TRIAL REGISTRATION NUMBER: N/A.

Radiographically normal knees with contralateral joint space narrowing display greater change in cartilage transverse relaxation time than those with normal contralateral knees: a model of early OA? - data from the Osteoarthritis Initiative (OAI).

OBJECTIVE: To develop a model of early osteoarthritis, by examining whether radiographically normal knees with contralateral joint space narrowing (JSN), but without contralateral trauma history, display greater longitudinal cartilage composition change (transverse relaxation time; T2) than subjects with bilaterally normal knees. METHODS: 120 radiographically normal knees (Kellgren Lawrence grade [KLG] 0) from the Osteoarthritis Initiative were studied. 60 case knees displayed definite contralateral radiographic knee osteoarthritis (KLG ≥ 2) whereas 60 reference subjects were bilaterally KLG0, and were matched 1:1 to cases based on age, sex, and BMI. All had multi-echo spin-echo MRI acquired at year (Y) 1 and 4 follow-up, with cartilage T2 being determined in superficial and deep cartilage layers across 16 femorotibial subregions. T2 across all regions was considered the primary analytic focus. RESULTS: Of 60 KLG0 case knees (30 female, age: 65.0 ± 8.8 y, BMI: 27.6 ± 4.4 kg/m2), 21/22/13/4 displayed contralateral JSN 0/1/2/3, respectively. The longitudinal increase in the deep layer cartilage T2 between Y1 and Y4 was significantly greater (P = 0.03; Cohen's D 0.50) in the 39 KLG0 case knees with contralateral JSN (1.2 ms; 95% confidence interval [CI] [0.4, 2.0]) than in matched KLG0 reference knees (0.1 ms; 95% CI [-0.5, 0.7]). No significant differences were identified in superficial T2 change. T2 at Y1 was significantly greater in case than in reference knees, particularly in the superficial layer of the medial compartment. CONCLUSIONS: Radiographically normal knees with contralateral, non-traumatic JSN represent an applicable model of early osteoarthritis, with deep layer cartilage composition (T2) changing more rapidly than in bilaterally normal knees. CLINICALTRIALS. GOV IDENTIFICATION: NCT00080171.

Hip muscle strength and protection against structural worsening and poor function and disability outcomes in knee osteoarthritis.

OBJECTIVE: Examine associations of hip abductor strength with (1) cartilage damage worsening in the tibiofemoral and patellofemoral compartments 2 years later, and (2) poor function and disability outcomes 5 years later. METHODS: Participants had knee osteoarthritis (K/L ≥ 2) in at least one knee. Hip abductor strength was measured using Biodex Dynamometry. Participants underwent 3.0T MRI of both knees at baseline and 2 years later. Baseline-to-2-year cartilage damage progression, defined as any worsening of WORMS cartilage damage score, was assessed at each tibiofemoral and patellofemoral surface. LLFDI (Late-Life Function and Disability Instrument) and Chair-Stand-Rate were recorded at baseline and 5-year follow-up; outcomes analyzed using quintiles. Poor outcomes were defined as remaining in the same low-function quintiles or being in a worse quintile at 5-year follow-up. We analyzed associations of baseline hip abductor strength with cartilage damage worsening and function and disability outcomes using multivariable log-binomial models. RESULTS: 275 knees from 164 persons [age = 63.7 (SD = 9.8) years, 79.3% women] comprised the structural outcome sample, and 187 persons [age = 64.2 (9.7), 78.6% women] the function and disability outcomes sample. Greater baseline hip abductor strength was associated with reduced risks of baseline-to-2-year medial patellofemoral and lateral tibiofemoral cartilage damage worsening [adjusted relative risks (RRs) range: 0.80-0.83) and with reduced risks of baseline-to-5-year poor outcomes for Chair-Stand-Rate and LLFDI Basic Lower-Extremity Function and Disability Limitation (adjusted RRs range: 0.91-0.94). CONCLUSION: Findings support a beneficial role of hip abductor strength for disease modification and for function and disability outcomes, and as a potential therapeutic target in managing knee osteoarthritis.

Automatic Detection of Aortic Valve Opening Using Seismocardiography in Healthy Individuals.

Accurate detection of fiducial points in a seismocardiogram (SCG) is a challenging research problem for its clinical application. In this paper, an automated method for detecting aortic valve opening (AO) instants using the dorso-ventral component of the SCG signal is proposed. This method does not require electrocardiogram (ECG) as a reference signal. After preprocessing the SCG, multiscale wavelet decomposition is carried out to get signal components in different wavelet subbands. The subbands having possible AO peaks are selected by a newly proposed dominant-multiscale-kurtosis- and dominant-multiscale-central-frequency-based criterion. The signal is reconstructed using selected subbands, and it is emphasized using the weights derived from the proposed relative squared dominant multiscale kurtosis. The Shannon energy followed by autocorrelation coefficients is computed for systole envelope construction. Finally, AO peaks are detected by a Gaussian-derivative-filtering-based scheme. The robustness of the proposed method is tested using clean and noisy SCG signals from the combined measurement of ECG, breathing, and SCG database. Evaluation results show that the method can achieve an average sensitivity of 94%, a prediction rate of 90%, and a detection accuracy of 86% approximately over 4585 analyzed beats.

Preferences for physical activity: a conjoint analysis involving people with chronic knee pain.

OBJECTIVE: To investigate individual preferences for physical activity (PA) attributes in adults with chronic knee pain, to identify clusters of individuals with similar preferences, and to identify whether individuals in these clusters differ by their demographic and health characteristics. DESIGN: An adaptive conjoint analysis (ACA) was conducted using the Potentially All Pairwise RanKings of all possible Alternatives (PAPRIKA) method to determine preference weights representing the relative importance of six PA attributes. Cluster analysis was performed to identify clusters of participants with similar weights. Chi-square and ANOVA were used to assess differences in individual characteristics by cluster. Multinomial logistic regression was used to assess associations between individual characteristics and cluster assignment. RESULTS: The study sample included 146 participants; mean age 65, 72% female, 47% white, non-Hispanic. The six attributes (mean weights in parentheses) are: health benefit (0.26), enjoyment (0.24), convenience (0.16), financial cost (0.13), effort (0.11) and time cost (0.10). Three clusters were identified: Cluster 1 (n = 33): for whom enjoyment (0.35) is twice as important as health benefit; Cluster 2 (n = 63): for whom health benefit (0.38) is most important; and Cluster 3 (n = 50): for whom cost (0.18), effort (0.18), health benefit (0.17) and enjoyment (0.18) are equally important. Cluster 1 was healthiest, Cluster 2 most self-efficacious, and Cluster 3 was in poorest health. CONCLUSIONS: Patients with chronic knee pain have preferences for PA that can be distinguished effectively using ACA methods. Adults with chronic knee pain, clustered by PA preferences, share distinguishing characteristics. Understanding preferences may help clinicians and researchers to better tailor PA interventions.

Cartilage loss in radiographically normal knees depends on radiographic status of the contralateral knee - data from the Osteoarthritis Initiative.

OBJECTIVE: To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis (OA), but without contralateral trauma history, display greater cartilage thickness loss than knees from subjects with bilaterally radiographically normal knees. METHODS: 828 radiographically normal knees (Kellgren Lawrence grade [KLG] 0) from the Osteoarthritis Initiative [OAI] were studied; 150 case knees displayed definite radiographic knee OA (KLG ≥ 2) contralaterally, and had MRI double echo steady state (DESS) images available at 12 and 48 month follow-up. 678 reference knees displayed KLG0 at the contralateral side. Cartilage thickness change was determined in femorotibial subregions and location-independent cartilage thinning scores were computed. Case and reference knees were compared using ANCOVA. RESULTS: Of the 150 KLG0 case knees, 108 had a contralateral KLG2 knee (50 without, and 58 with joint space narrowing [JSN]), 31 a KLG3 and 11 a KLG4 knee. The cartilage thinning score tended to be greater in case than reference knees; the cartilage thinning score in KLG0 case knees with contralateral radiographic JSN (-858 µm; [95% confidence interval -1016, -701 µm]) was significantly greater (P = 0.0012) than that in bilaterally KLG0 reference knees (-634 µm; [-673, -596 µm]), whereas KLG0 knees with contralateral KLG2 without JSN only showed relatively small thinning scores (-530 µm, [-631, -428 µm]). Region-specific analysis suggested greater rates of cartilage loss in case than in reference knees in the lateral, rather than medial, femorotibial compartment. CONCLUSIONS: Radiographically normal knees with contralateral JSN may serve as a human model of early OA, for testing disease modifying drugs in clinical trials designed to prevent cartilage loss before the onset of radiographic change. CLINICALTRIALS. GOV IDENTIFICATION: NCT00080171.

Serum zinc, copper and iron status of children with coeliac disease on three months of gluten-free diet with or without four weeks of zinc supplements: a randomised controlled trial.

Data about the effect of zinc supplementation with gluten-free diet on normalisation of plasma zinc, copper and iron in patients with coeliac disease are scanty. We evaluated the effect of zinc supplementation on serum zinc, copper and iron levels in patients with coeliac disease, by randomising 71 children newly diagnosed with coeliac disease into two groups: Group A = gluten-free diet (GFD); and Group B = gluten-free diet with zinc supplements (GFD +Zn). The rise in iron and zinc was significantly higher in the latter, but the mean rise of copper levels was slightly higher in the former, but the difference was not significant.

Predictive and concurrent validity of cartilage thickness change as a marker of knee osteoarthritis progression: data from the Osteoarthritis Initiative.

OBJECTIVE: To investigate the predictive and concurrent validity of magnetic resonance imaging (MRI)-based cartilage thickness change between baseline (BL) and year-two (Y2) follow-up (predictive validity) and between Y2 and Y4 follow-up (concurrent validity) for symptomatic and radiographic knee osteoarthritis (OA) progression during Y2→Y4. METHODS: 777 knees from 777 Osteoarthritis Initiative (OAI) participants (age: 61.3 ± 9.0 years, BMI: 30.1 ± 4.8 kg/m2) with Kellgren Lawrence (KL) grade 1-3 at Y2 (visit before progression interval) had cartilage thickness measurements from 3T MRI at BL, Y2 (n = 777), and Y4 (n = 708). Analysis of covariance and logistic regression were used to assess the association of pain progression (≥9 WOMAC units [scale 0-100], n = 205/572 with/without progression) and radiographic progression (≥0.7 mm minimum joint space width (mJSW) loss, n = 166/611 with/without progression) between Y2 and Y4 with preceding (BL→Y2) and concurrent (Y2→Y4) change in central medial femorotibial (cMFTC) compartment cartilage thickness. RESULTS: Symptomatic progression was associated with concurrent (Y2→Y4: -305 ± 470 µm vs -155 ± 346 µm, Odds ratios (OR) = 1.5 [1.2, 1.7]) but not with preceding cartilage thickness loss in cMFTC (-150 ± 276 µm vs -151 ± 299 µm, OR = 0.9 95% CI: [0.8, 1.1]). Radiographic progression, in contrast, was significantly associated with both concurrent (-542 ± 550 µm vs -98 ± 255 µm, OR = 3.4 [2.6, 4.3]) and preceding cMFTC thickness loss (-229 ± 355 µm vs -130 ± 270 µm, OR = 1.3 [1.1, 1.5]). CONCLUSIONS: These results extend previous reports that did not discern predictive vs concurrent associations of cartilage thickness loss with OA progression. The observed predictive and concurrent validity of cartilage thickness loss for radiographic progression and observed concurrent validity for symptomatic progression provide an important step in qualifying cartilage thickness loss as a biomarker of knee OA progression. CLINICALTRIALS. GOV IDENTIFICATION: NCT00080171.

Knee tissue lesions and prediction of incident knee osteoarthritis over 7 years in a cohort of persons at higher risk.

OBJECTIVE: Among high risk individuals, whether knee lesions in tissues involved in osteoarthritis (OA) can improve prediction of knee OA is unclear. We hypothesized that models predicting (1) incident osteophytes and (2) incident osteophytes and joint space narrowing can be improved by including symptoms or function, and further improved by lesion status. DESIGN: In Osteoarthritis Initiative (OAI) participants with normal knee X-rays, we assessed cartilage damage, bone marrow lesions (BMLs), and menisci. Cox proportional hazards models were used to develop risk prediction models for risk of each outcome. Nested models (increasingly larger baseline covariable sets) were compared using likelihood ratio tests and Schwarz Bayesian Information Criterion (SBC). Model discrimination used receiver operating characteristic (ROC) curves and area under the curve (AUC). RESULTS: In 841 participants [age 59.6, body mass index (BMI) 26.7, 55.9% women] over up to 7 years follow-up, each larger set improved prediction (+hand OA, injury, surgery, activities; +symptoms/function). Prediction was further improved by including cartilage damage both compartments, BMLs both compartments, meniscal tear, meniscal extrusion, sum of lesion types, number of subregions with cartilage damage, number of subregions with BMLs, and (concurrently) subregion number with cartilage damage, subregion number with BMLs, and meniscal tear. AUCs were ≥0.80 for both outcomes for number of subregions with cartilage damage and the combined model. CONCLUSIONS: Among persons at higher risk for knee OA with normal X-rays, MRI tissue lesions improved prediction of mild as well as moderate disease. These findings support that disease onset is likely occurring during the "high-risk" period and encourage a reorientation of approach.

Varus thrust during walking and the risk of incident and worsening medial tibiofemoral MRI lesions: the Multicenter Osteoarthritis Study.

OBJECTIVE: To determine the association of varus thrust during walking to incident and worsening medial tibiofemoral cartilage damage and bone marrow lesions (BMLs) over 2 years in older adults with or at risk for osteoarthritis (OA). METHOD: Subjects from the Multicenter Osteoarthritis Study (MOST) were studied. Varus thrust was visually assessed from high-speed videos of forward walking trials. Baseline and two-year MRIs were acquired from one knee per subject and read for cartilage loss and BMLs. Logistic regression with generalized estimating equations was used to estimate the odds of incident and worsening cartilage loss and BMLs, adjusting for age, sex, race, body mass index (BMI), and clinic site. The analysis was repeated stratified by varus, neutral, and valgus alignment. RESULTS: 1007 participants contributed one knee each. Varus thrust was observed in 29.9% of knees. Knees with thrust had 2.17 [95% CI: 1.51, 3.11] times the odds of incident medial BML, 2.51 [1.85, 3.40] times the odds of worsening medial BML, and 1.85 [1.35, 2.55] times the odds of worsening medial cartilage loss. When stratified by alignment, varus knees also had significantly increased odds of these outcomes. CONCLUSION: Varus thrust observed during walking is associated with increased odds of incident and worsening medial BMLs and worsening medial cartilage loss. Increased odds of these outcomes persist in varus-aligned knees.