Une alternative à la chromatographie pour la détection de la macroprolactine : calcul du rapport de deux immunodosages de la prolactine : Immulite 2000® et Kryptor®

Macroprolactin is a high molecular mass form of prolactin with minimal bioactivity in vivo. The presence of macroprolactin must be considered for the differential diagnosis of hyperprolactinemia because prolactin-immunoassays present various reactivity with macroprolactin. So we compared to the reference technique (size-exclusion chromatography) a new screening test: calculation of the ratio between results obtained from two prolactin assays: Immulite^® with high cross reactivity with macroprolactin and Kryptor^® with no reactivity. In this study, serums from 69 patients with various macroprolactinemia (between 8 and 88% with chromatography) were selected and the ratio of the results of two prolactin assays was calculated for 49 hyperprolactinemic serums (prolactinemia > 636 mUI/l, Immulite 2000^®). According to ROC curves analysis, a low Immulite^®/Kryptor^® ratio (< 1.45) indicates the presence of less than 20% of macroprolactin (sensitivity = 100% specificity = 85%), and a high ratio (> 1.80) indicates the presence of more than 50% of macroprolactin (sensitivity = 95%, specificity = 100%). However, this screening test must be confirmed by size-exclusion chromatography for the rare samples presenting an Immulite^®/Kryptor^® ratio between 1.45 and 1.80.     

Homocystéine et paramètres du syndrome métabolique et du risque cardiovasculaire chez 2045 militaires : étude EPIMIL

The aim of this present study is to investigate a possible relationship between plasma homocystein and biological indicators of metabolic syndrome and cardiovascular risk in a prospective epidemiological study; EPIMIL involving 2045 military subjects 20–58 years of age. Homocysteinemia measurements have been performed using automated chemiluminescent enzyme immunoassay on Immulite 2000^TM (DPC). According to NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel) definition, the prevalence of metabolic syndrome was 9%. Homocysteinemia was slightly related to some markers as cholesterol (R = 0,04, p = 0,05), triglycerides (R = 0,06, p = 0,004), free fatty acids (R = 0,06, P = 0,004). When fasting homocysteinemia above 15 μmol/l (7,5% of the population), there is no relationship with syndrome metabolic components and cardiovascular risk biological markers except for cholesterol and blood pressure. The follow up of the EPIMIL population for ten years would predict if plasma homocysteine is or not an independent factor in the complex pathomecanism of atherosclerosis.     

Preliminary investigation of rate of torque development deficits following total knee arthroplasty

BackgroundTo assess changes in maximal strength and rate of torque development (RTD) following TKA, and examine the relationships between these measures and physical function.MethodsThirty-five TKA patients and 23 controls completed isometric knee extensor torque testing preoperatively, 1, and 6 months after surgery. Maximal strength was calculated as the peak torque during a maximal voluntary isometric contraction (MVIC) of the knee extensor muscles, peak RTD (RTD_peak) was calculated as the maximum value from the 1st derivative of the isometric knee extension torque data, RTD_25% and RTD _50% were calculated as the change in force over the change in time from force onset to 25% and 50% MVIC. Physical function was measured using a timed-up-and-go (TUG) and stair climbing test (SCT).ResultsRTD was significantly lower in the TKA group, at all-time points, compared to the Controls. MVIC and RTD significantly decreased 1-month following surgery (p = 0.000 for all measures). RTD_peak measures added to linear regressions with strength improved the prediction of TUG scores (p = 0.006) and the SCT scores (p = 0.015) 1-month post-surgery. Adding RTD_50% to the regression model, following MVIC, improved predicting both TUG (p = 0.033) and SCT (p = 0.024). At 6-months, the addition of RTD_25% to the regression model, following MVIC, improved the prediction of TUG (p = 0.037) and SCT (p = 0.036).ConclusionFollowing TKA, physical function is influenced by both the maximal strength and the rate of torque development of the knee extensors, and the prediction of function is improved with the addition of RTD compared to that of maximal strength alone.     

Tumor-associated antigens in systemic sclerosis and systemic lupus erythematosus: Associations with organ manifestations,immunolaboratory markers and disease activity indices

BackgroundSome tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected increased production of CA15-3, CA19-9 and CA125 in rheumatoid arthritis (RA). The production of some TAAs may also be increased in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and other connective tissue diseases. Some of these TAAs contain sialylated carbohydrate motifs and they are involved in tumor-associated cell adhesion and metastasis.ObjectivesWe assessed levels of TAAs in the sera of SSc, SLE patients, patients with infectious diseases and healthy subjects. Serum TAA levels were correlated with each other, as well as with disease activity markers and organ involvement.MethodsTAAs including CEA, CA15-3, CA72-4, CA125 and CA19-9 were assessed by immunoassay in the sera of 92 patients with SSc, 40 patients with SLE, 50 age- and sex-matched healthy controls, as well as with 40 patients with current bacterial or viral infections. Normal upper limits for these TAAs were 3.4 mg/l, 25 kU/l, 6.9 kU/l, 35 kU/l and 34 kU/l, respectively.ResultsThere were significantly more SSc patients showing abnormally high levels of CA19-9 (8.8% vs 2.0%), CA125 (11.0% vs 6.0%) and CA15-3 (28.4% vs 14.0%) in comparison to controls (p < 0.05). In SLE, significantly more patients had elevated levels of CEA (32.5% vs 20.0%), CA19-9 (7.5% vs 2.0%), CA125 (15.0% vs 6.0%) and CA72-4 (15.0% vs 8.0%) than did controls (p < 0.05). The mean absolute serum levels of CEA (6.6 ± 1.7 vs 1.8 ± 1.4 mg/l) and CA15-3 (22.9 ± 1.8 vs 18.6 ± 2.2 kU/l) were also significantly higher in SSc compared to controls (p < 0.05). We found numerous correlations between the serum levels of different TAAs within the SSc and SLE population. Among SSc patients, serum CEA (R = 0.290; p = 0.005), CA15-3 (R = 0.260; p = 0.020) and CA19-9 (R = 0.257; p = 0.013) correlated with renal involvement. Serum CA15-3 also correlated with joint involvement (R = 0.329; p = 0.003), ANA positivity (R = 0.288; p = 0.010) and CRP levels (R = 0.407; p < 0.001). Within the SLE population, serum CA72-4 correlated with central nervous involvement (R = 0.624; p = 0.004) and CA125 correlated with the SLEDAI composite activity index (R = 0.666; p = 0.002). Patients with infections exerted serum TAA patterns similar to healthy controls.ConclusionThe concentration of some TAAs may be elevated in the sera of patients with SSc or SLE in comparison to healthy subjects. Pathogenically, most of these TAAs contain carbohydrate motifs and thus they may be involved in inflammation-associated adhesive events. Furthermore, the production of some TAAs may correlate with organ involvement or disease activity in scleroderma or lupus.     

Association between KIR gene polymorphisms and rheumatoid arthritis susceptibility: A meta-analysis

ObjectivesThe results of studies on association between KIR (killer cell immunoglobulin-like receptors) polymorphisms and susceptibility to RA (rheumatoid arthritis) are inconsistent. To comprehensively evaluate the effect of KIR polymorphisms on the risk of RA, a meta-analysis was carried out.MethodsThe Web of Science, PubMed, the Chinese Biomedical Database (CBM) and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to select studies on the association between KIR polymorphisms and RA. The odds ratio (OR) with 95% confidence interval (95%CI) was obtained.ResultsNine qualified case–control studies were included in this meta-analysis. The results showed there were two positive associations of 2DL1, 2DS1 (OR_2DL1 = 2.20, 95%CI = 1.20–4.01, P_raw = 0.01, P_FDR = 0.03; OR_2DS1 = 1.84, 95%CI = 1.19–2.85, P_raw = 0.006, P_FDR = 0.018) and one negative association of 2DL3 (OR_2DL3 = 0.42, 95%CI = 0.22–0.79, P_raw = 0.006, P_FDR = 0.018) with susceptibility to RA in East Asians, but not in Caucasians.ConclusionThe current meta-analysis provides evidence that 2DL3 might be a potential protective factor and 2DL1, 2DS1 might be risk factors for RA in East Asians but not in Caucasians.     

Contrôle de qualité des greffons de sang placentaire décongelés : résultats d’une étude multicentrique

PurposeToday, haematopoietic stem cell graft from placental blood concerns more than 15 % of allogeneic grafts. An inter-laboratory study of the quality control of defrosted cord blood units has been coordinated by the French society for cell and tissue bioengineering (SFBCT), with the cord blood bank of Bourgogne Franche-Comté and controlled by the French health products safety agency (Afssaps). The aim of this study is to ensure the inter-laboratory reproducibility of the quality controls practised by the banks during defrosting. The cellular outputs were analyzed according to the defrosting techniques, according to the method used in flow cytometry: single-platform (SP) versus double-platform (DP), or the product nature, i.e. in total blood or miniaturized.MethodsForty-two units of placental blood (USP), which were out of range were provided for defrosting to 14 participating sites. USP were defrosted and controlled according to the procedures of each bank. Once the USP is defrosted, a part of the product was controlled by the site and the other part by Afssaps. Following controls were carried out: numeration of the total nucleated cells (TNC) and of CD34+ cells (made by a SP method in Afssaps) and functional assay.ResultsConcerning TNC, the defrosting sites obtained a cellular output of 94 % ± 28 in day 0 compared with an output of 72 % ± 24 in Afssaps showing a rather good stability of the USP transmitted with an average deviation of 23 % ± 22. The freezing process with or without reduction of volume does not affect this variation. Concerning the numeration of CD34+ cells, the average deviation between the participating sites and Afssaps was 29 % ± 23 compared with 21 % ± 16 for the sites using a SP method against 47 % ± 25 for those using a DP method. The CD34+ outputs are equal to 82 % ± 60 in day 0 for the participating sites against 52 % ± 20 for Afssaps. For the sites using a DP method, it is stressed that this output is particularly high with a rate of 126 % ± 90 (n = 15) whereas it is 62 % ± 20 (n = 32) for the sites using a SP method.ConclusionThese results underline a good stability of viable CD34+ cells and a greater reliability of the SP methods for the CD34+ cell numeration for these defrosted USP. Lastly, the results of the functional assay regarding the average clonogenicities (equal to 15 %) reinforce the conclusions on the quality of the defrosted products.     

Dosage plasmatique des D-dimères sur Integra 800® : comparaison avec le dosage sur Vidas® dans le diagnostic d'exclusion des maladies veineuses thromboemboliques

The D-dimer quantitative test is an exclusive screening tool used by the emergency departments for the exclusion of Deep Venous Thrombosis diseases (DVT). Its negative predictive value is closed to 100%. We compared the diagnostic performance of the D-dimer assay Tinaquant^® performed on an Integra 800^® to the reference Elisa D-dimer assay Vidas^®, which is routinely used in our laboratory as reference test. Interassay reproducibilility (CV) for Tinaquant^® is: 2.34% and 2.05% for levels of 1010 and 4830 ng/ml respectively. We investigated 250 patients with the two tests simultaneously. The correlation obtained through a linear regression (R = 0.86) gives the equation: Y (Integra^®) = 1.11 × (Vidas^®) – 72. The mean D-dimer Vidas^® are: 1337 ± 1700 ng/ml vs. Integra^®: 1496 ng/ml ± 2379. Ninety percent of the results are concordant at a cutoff of 500 ng/ml. Among the 25 discordant results, 18 are Vidas^®(+)/Tinaquant^®(–) showing a better specificity for the Tinaquant^® test, which is confirmed by imaging results for DVT diagnosis. Only 7 of the 25 give a better specificity for Vidas^®. Tinaquant^® D-dimer assay demonstrated interesting performances in this study regarding the practicability and the efficiency of the test. It appears to be suitable for the exclusion of DVT diseases and should be studied throughout a larger number of outpatients.     

Retentissement du tabagisme maternel sur le comportement du nouveau-né : dosage des métabolites urinaires de la nicotine chez la mère et le nouveau-né

Influence of maternal smoking on newborn's behaviour: determination urinary nicotine metabolites levels in mothers and infants.Objective. – Effects of smoking during pregnancy on newborn's behaviour at 2 or 3 days. Intoxication? Withdrawal?Population and method. – Urinary cotinine levels were measured using DPC^® technique in 142 mothers during labour and in their 138 normal, full-term newborns kept with their mothers at about 3 days. Infants' Finnegan scores were estimated, Lamour/Barraco tests, too.Results. – There are significant correlations: maternal cotinine (ng/mg) = 382,67 + 264,79 cigarettes/day, R = 0,70, P < 0,001; newborn cotinine (ng/mg) = 74,28 + 68,49 cigarettes/day, R = 0,69, P < 0,001; newborn cotinine (ng/mg) = 57,59 + 0,18 maternal cotinine (ng/mg), R = 0,73, P < 0,001. Newborns' cotinine concentrations (47% corresponds with smokers' levels) are with breast-milk 4,94 times lower than that of their mothers vs 3,65 with artificial milk. Incidence of colic increases (P = 0,008) and the neurologic scores average decreases (P = 0,059).Conclusions. – Newborns' high cotinine levels, digestive and neurologic symptoms modification suggest tobacco intoxication. Therefore withdrawal would appear later. Breast-milk seems to accelerate cotinine elimination.     

L’âge des culots globulaires transfusés influence-t-il toujours le pronostic des patients en réanimation ?

ObjectiveFew studies have shown that aged packed red blood cells (RBC) transfusion negatively influenced the outcome of ICU patients, probably related to storage lesions which could be decreased by leukodepletion of RBC. The purpose of this study was to evaluate the impact of aged leukodepleted-RBC pack, on the outcome of ICU patients.DesignRetrospective, observational, cohort study in a Medical Intensive Care Unit.PatientsConsecutive patients admitted during the years 2005 and 2006, and requiring a transfusion. We recorded patient's demographic data, number of RBC unit and age of each RBC, length of ICU, mortality during ICU stay.ResultsFive hundred and thirty-four patients were included with global mortality was 26.6%, length of stay in ICU six days (3–14) and SAPS II 48 (35–62). RBC equaling to 5.9 were transfused per patients (22.7% < 14 days and 57.3% < 21 days). The number of RBC was significantly higher in the dead patients group, but the rate of RBC stored less than 21 days was not different (54% versus 60%; p = 0.21). In a multivariate logistic model, independent predictors of ICU death were SAPS II (OR = 1.02 per point, p < 0.001), number of RBC (OR = 1.08 per RBC, p < 0.001), length of stay in ICU (p < 0.001). Similar results were obtained while introducing the age of RBC as time dependent covariates in a multivariate Cox's model.ConclusionsRBC transfused in our ICU are old. The ICU outcome is independently associated with the number of leucodepleted RBC transfused, but not with their age.     

Continuous monitoring of electromyography (EMG), mechanomyography (MMG), sonomyography (SMG) and torque output during ramp and step isometric contractions

In this study we simultaneously collected ultrasound images, EMG, MMG from the rectus femoris (RF) muscle and torque signal from the leg extensor muscle group of nine male subjects (mean ± SD, age = 30.7 ± .4.9 years; body weight = 67.0 ± 8.4 kg; height = 170.4 ± 6.9 cm) during step, ramp increasing, and decreasing at three different rates (50%, 25% and 17% MVC/s). The muscle architectural parameters extracted from ultrasound imaging, which reflect muscle contractions, were defined as sonomyography (SMG) in this study. The cross-sectional area (CSA) and aspect ratio between muscle width and thickness (width/thickness) were extracted from ultrasound images. The results showed that the CSA of RF muscles decreased by 7.25 ± 4.07% when muscle torque output changed from 0% to 90% MVC, and the aspect ratio decreased by 41.66 ± 7.96%. The muscle contraction level and SMG data were strongly correlated (R² = 0.961, P = 0.003, for CSA and R² = 0.999, P < 0.001, for width/thickness ratio). The data indicated a significant difference (P < 0.05) in percentage changes for CSA and aspect ratio among step, ramp increasing, and decreasing contractions. The normalized EMG RMS in ramp increasing was 8.25 ± 4.00% higher than step (P = 0.002). The normalized MMG RMS of step contraction was significantly lower than ramp increasing and decreasing, with averaged differences of 12.22 ± 3.37% (P = 0.001) and 12.06 ± 3.37% (P = 0.001), respectively. The results of this study demonstrated that the CSA and aspect ratio, i.e., SMG signals, can provide useful information about muscle contractions. They may therefore complement EMG and MMG for studying muscle activation strategies under different conditions.     

Can a 15 m-overground wheelchair sprint be used to assess wheelchair-specific anaerobic work capacity?

ObjectiveTo evaluate whether outcomes based on stopwatch time and power output (PO) over a 15 m-overground wheelchair sprint test can be used to assess wheelchair-specific anaerobic work capacity, by studying their relationship with outcomes on a Wingate-based 30 s-wheelchair ergometer sprint (WAnT).MethodsAble-bodied persons (N = 19, 10 men, aged 18–26 y) performed a 15 m overground sprint test in an instrumented wheelchair and a WAnT. 15 m-outcomes were based on stopwatch time (time and mean velocity over 15 m) and on PO (primary outcome: highest mean unilateral PO over successive 5 s-intervals (P5-15m)). WAnT-outcomes were mean unilateral PO over 30 s and the highest mean unilateral PO over successive 5 s-intervals. Correlation coefficients (Pearson's r) and coefficients of determination (R²) were calculated between 15 m-sprint outcomes and WAnT-outcomes.ResultsTime over 15 m (7.2 s (±1.0)) was weakly related to WAnT-outcomes (r = −0.61 and −0.60, R² = 0.38 and 0.36, p < 0.01), similar to mean velocity over 15 m (2.1 m·s⁻¹ (±0.3), R² = 0.43 and 0.39, p < 0.01). P5-15m (38.1 W (±14.0)) showed a moderate relationship to WAnT-outcomes (r = 0.77 and 0.75, R² = 0.59 and 0.56, p < 0.001).ConclusionsIt seems that outcomes based on stopwatch time over a 15 m-overground sprint cannot be used to assess wheelchair-specific anaerobic work capacity, in contrast to an outcome based on PO (P5-15m). The 15 m-sprint with an instrumented wheel can be implemented in rehabilitation practice and research settings when WAnT equipment is not available, although care is needed when interpreting P5-15m as an outcome of anaerobic work capacity given that it seems more skill-dependent than the WAnT.     

Cement penetration after patella venting

There is a high rate of patellofemoral complications following total knee arthroplasty. Optimization of the cement–bone interface by venting and suction of the tibial plateau has been shown to improve cement penetration. Our study was designed to investigate if venting the patella prior to cementing improved cement penetration.Ten paired cadaver patellae were allocated prior to resurfacing to be vented or non-vented. Bone mineral density (BMD) was measured by DEXA scanning. In vented specimens, a 1.6 mm Kirschner wire was used to breach the anterior cortex at the center. Specimens were resurfaced with standard Profix instrumentation and Versabond bone cement (Smith and Nephew PLC, UK). Cement penetration was assessed from Faxitron and sectioned images by a digital image software package (ImageJ V1.38, NIH, USA). Wilcoxon rank sum test was used to assess the difference in cement penetration between groups. The relationship between BMD and cement penetration was analyzed by Pearson correlation coefficient.There was a strong negative correlation between peak BMD and cement penetration when analyzed independent of experimental grouping (r² = ? 0.812, p = 0.004). Wilcoxon rank sum testing demonstrated no significant difference (rank sum statistic W = 27, p = 0.579) in cement penetration between vented (10.53% ± 4.66; mean ± std dev) and non-vented patellae (11.51% ± 6.23; mean ± std dev). Venting the patella using a Kirschner wire does not have a significant effect on the amount of cement penetration achieved in vitro using Profix instrumentation and Versabond cement.     

Genetic polymorphisms in TNFSF13 and FDX1 are associated with IgA nephropathy in the Han Chinese population

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, and its pathogenesis is influenced by both genetic and environmental factors. In this study, we evaluated 23 tag single-nucleotide polymorphisms (tSNPs) in 21 IgAN-associated genes, in 200 subjects with IgAN and 310 healthy gender- and age-matched unrelated control subjects with no history of renal disease or hypertension. Using the co-dominant model, we found that two genotypes of rs3803800 in TNFSF13 were associated with an increased risk of IgAN: “GA” (OR = 1.03, 95% CI = 0.71–1.51, p = 0.018) and “AA” (OR = 2.45, 95% CI = 1.29–4.65, p = 0.018). The “AA” genotype was also associated with an increased risk of IgAN in the recessive model (OR = 2.41, 95% CI = 1.30–4.46, p = 0.018), as was the genotype “AA” rs10488764 in FDX1 (OR = 1.88, 95% CI = 1.01–3.53, p = 0.048). Interestingly, we found that the allele “A” of rs3803800 in TNFSF13 is associated with a decreased risk of IgAN in females (OR = 0.43, 95% CI = 0.20–0.95, p = 0.009), but with an increased risk in males (OR = 1.78, 95% CI = 0.86–3.66, p = 0.009). Our findings, combined with previously reported results, suggest that TNFSF13 and FDX1 have potential roles in IgAN in the Han Chinese population. This information may be useful in the development of early prognostics for IgAN.     

The T &gt; A (rs11646213) gene polymorphism of cadherin-13 (CDH13) gene is associated with decreased risk of developing hypertension in Mexican population

Hypertension is a major public health problem affecting about 30% of the adult population and is associated with an increased risk of developing metabolic and cardiovascular disease. Recent reports have shown that the T-cadherin receptor characteristically expressed on endothelial and vascular smooth muscle cells is involved in hypertension. The aim of the present study was to evaluate the role of cadherin-13 (CDH13) gene polymorphisms as susceptibility markers for hypertension in Mexican population. Six CDH13 polymorphisms (rs11646213, rs11646411, rs6563943, rs3096277, rs3784990 and rs254340) were genotyped by 5′ exonuclease TaqMan assays in a group of 644 hypertensive and 765 non-hypertensive individuals. Under co-dominant, recessive, and additive models, the CDH13 T > A (rs11646213) polymorphism was associated with decreased risk of developing hypertension when compared to non-hypertensive individuals (OR = 0.61, 95% CI: 0.42–0.89, P_co-dom = 0.019; OR = 0.63, 95% CI: 0.46–0.87, P_res = 0.005; OR = 0.80, 95% CI: 0.66–0.96, P_add = 0.016, respectively). All models were adjusted by gender, age, body index mass, type II diabetes mellitus, alcohol consumption, dyslipidemia and smoking habit. Linkage disequilibrium analysis showed one haplotype (TCACGG) with decreased frequency in hypertensive when compared to non-hypertensive individuals (OR = 0.52, 95% CI: 0.33–0.82, P = 0.0053). In summary, our data suggests that the CDH13 T > A (rs11646213) polymorphism is associated with decreased risk of developing hypertension in the Mexican population. In addition, it was possible to distinguish one haplotype associated with decreased risk and two for increased risk of develop hypertension.     

Determinants of vitamin D status in healthy men and women aged 40–80 years

ObjectivesTo determine the contribution of life style and health related factors on vitamin D status in middle-aged and older men and women.Study designA cross-sectional single-center study in 400 male subjects (40–80 years) and 402 postmenopausal female subjects (56–73 years), conducted in a University Medical Center in the central part of the Netherlands (52 degrees northern latitude).Main outcome measuresMedical history, vitamin D, calcium and alcohol intake, physical activity, Body Mass Index, Blood pressure, smoking, total fat body mass and total lean body mass were measured using DEXA. Laboratory analysis included 25-hydroxyvitamin D (25OHD) and sex hormones.ResultsThirty-six percent of men and 51% of women had 25OHD less than 50 nmol/L. In summertime men had significant higher 25OHD as compared to women (81.5 vs 53.3 nmol/L, P = .000) but this difference disappeared come winter. In a saturated model, male gender (B = .16, P = .008), and season (summer vs winter B = .30, P = .000) remained statistically significant. In men, physical activity and season explained 21% of the variance. In women, household physical activity (B = .13, P = .03), sport physical activity (B = .02, P = .02) and estradiol (B = ?.003, P = .048) remained in the model,.ConclusionIn healthy middle-aged and older men and postmenopausal women, male gender and season were important predictors of vitamin D status. In men, physically activity and season, explained 21% of the variance in vitamin D status. In women, physical activity and estradiol explained 9.3% of the variance in vitamin D.     

Assessment of adaptive walking performance

Although mostly negative aspects are reported to be associated with gait variability, irregular walking is needed when walking performance has to be adapted to specific environmental conditions. The aim of this study was to evaluate the test–retest reliability and discriminative ability of a measure to assess adaptive walking performance and to identify parameters associated with test performance in young and elderly subjects. Eighteen older (mean age 78.1 years) and 19 young women (mean age 30.8 years) were instructed to walk as precisely as possible over a defined course targeting 26 arbitrarily positioned rectangle boxes fixed on an instrumented walk way with embedded pressure sensors. ICC_1,1 of 0.79 demonstrated sufficient reliability in the cohort of older women. Targeting was significantly worse (or deviation was larger) in older women than in young women (mean 3.20 cm versus 2.27 cm, p = 0.005). Mean gait speed of the older women was higher during the test (0.50 m/s versus 0.40 m/s, p = 0.020), but not during unconstrained walking (1.15 m/s versus 1.50 m/s, p < 0.001). The deviation measure classified 78% of the subjects into correct age group (sensitivity 67%, specificity 90%, p = 0.003). Adaptive walking performance was associated with parameters describing physical performance as well as with cognitive executive function. This study shows that this test of adaptive walking performance is a reliable measure of irregular walking with ability to discriminate between young and older subjects. Our results suggest that older persons might try to camouflage their lack of accuracy during adaptive walking by higher gait speed.     

Low-level laser therapy using the minimally invasive laser needle system on osteoporotic bone in ovariectomized mice

This study tested the effectiveness of low-level laser therapy (LLLT) in preventing and/or treating osteoporotic trabecular bone. Mice were ovariectomized (OVX) to induce osteoporotic bone loss. The tibiae of eight OVX mice were treated for 5 days each week for 2 weeks by LLLT (660 nm, 3 J) using a minimally invasive laser needle system (MILNS) which is designed to minimize loss of laser energy before reaching bone (LASER group). Another eight mice received a sham treatment (SHAM group). Structural parameters of trabecular bone were measured with in vivo micro-computed tomography images before and after laser treatment. After LLLT for 2 weeks, the percentage reduction (%R) was significantly lower in BV/TV (bone volume fraction) and Tb.N (trabecular number, p < 0.05 and p < 0.05) and significant higher in Tb.Sp (trabecular separation) and SMI (structure model index, p < 0.05 and p < 0.05) than in the SHAM group. The %R in BV/TV at sites directly treated by LLLT was significantly lower in the LASER group than the SHAM group (p < 0.05, p < 0.05). These results indicated that LLLT using MILNS may be effective for preventing and/or treating trabecular bone loss and the effect may be site-dependent in the same bone.     

EphA2 knockdown attenuates atherosclerotic lesion development in ApoE−/− mice

BackgroundThe inflammatory response of vascular endothelial cells plays important roles in the initiation and progression of atherosclerotic lesions. EphA2 receptor activation promotes the endothelial cell inflammatory response, and its expression is increased in the endothelial cell layer of atherosclerotic plaques. However, the association between EphA2 and atherosclerosis has not been determined.MethodsEight-week-old male ApoE^−/− mice were systemically infected with adenoassociated virus serotype 9 carrying a small hairpin RNA specifically targeting the EphA2 gene to knock down EphA2 expression in aortic endothelial cells. These mice were then fed a high-cholesterol diet for 12 weeks. Blood was collected for the measurement of plasma lipids. The aortas were harvested to evaluate the atherosclerotic lesion size, macrophage components, and expression of proinflammatory genes using Oil Red O staining, immunofluorescence staining, and molecular biology analysis.ResultsThe lesions formed in the entire aorta and aortic sinus of the ApoE^−/− mice with EphA2 knockdown were significantly smaller than those in the control mice (10.7% ± 3.1% versus 25.1% ± 4.2%; 0.51 ± 0.02 mm² versus 0.85 ± 0.03 mm²; n = 10; P < .05). Furthermore, the lesions in the ApoE^−/− mice with EphA2 knockdown displayed reduced inflammation compared with the control mice, as reflected by the decreased macrophage infiltration (8.2% ± 2.9% versus 22.7% ± 4%; n = 10; P < .05); decreased nuclear factor-κβ activation; and diminished expression of vascular cell adhesion molecule-1, E-selectin, and monocyte chemotactic protein-1 (all P < .05).ConclusionsOur data demonstrate that the EphA2 receptor silencing attenuates the extent and inflammation of atherosclerotic lesions in ApoE^−/− mice. Thus, EphA2 knockdown in endothelial cells represents a novel therapeutic strategy for patients with atherosclerosis.     

Micro-CT evaluation of bone defects: Applications to osteolytic bone metastases,bone cysts,and fracture

Bone defects can occur in various forms and present challenges to performing a standard micro-CT evaluation of bone quality because most measures are suited to homogeneous structures rather than ones with spatially focal abnormalities. Such defects are commonly associated with pain and fragility. Research involving bone defects requires quantitative approaches to be developed if micro-CT is to be employed. In this study, we demonstrate that measures of inter-microarchitectural bone spacing are sensitive to the presence of focal defects in the proximal tibia of two distinctly different mouse models: a burr-hole model for fracture healing research, and a model of osteolytic bone metastases. In these models, the cortical and trabecular bone compartments were both affected by the defect and were, therefore, evaluated as a single unit to avoid splitting the defects into multiple analysis regions. The burr-hole defect increased mean spacing (Sp) by 27.6%, spacing standard deviation (SpSD) by 113%, and maximum spacing (Sp_max) by 72.8%. Regression modeling revealed SpSD (β = 0.974, p < 0.0001) to be a significant predictor of the defect volume (R² = 0.949) and Sp_max (β = 0.712, p < 0.0001) and SpSD (β = 0.271, p = 0.022) to be significant predictors of the defect diameter (R² = 0.954). In the mice with osteolytic bone metastases, spacing parameters followed similar patterns of change as reflected by other imaging technologies, specifically bioluminescence data which is indicative of tumor burden. These data highlight the sensitivity of spacing measurements to bone architectural abnormalities from 3D micro-CT data and provide a tool for quantitative evaluation of defects within a bone.     

The MHC2TA 1614 C&gt;G gene polymorphism is associated with risk of developing acute coronary syndrome

BackgroundInflammation plays an essential role in the development and progression of atherosclerotic lesions. The major histocompatibility complex class II trans-activator (MHC2TA) is considered an important molecule in the inflammatory process regulation. The aim of the present study was to evaluate the role of MHC2TA gene polymorphisms as susceptibility markers for acute coronary syndrome (ACS).MethodsThree polymorphisms (−168 A>G, 1614 C>G, and 2536 G>A) of the MHC2TA gene were analyzed by 5′ exonuclease TaqMan genotyping assays in a group of 297 patients with ACS and 283 healthy controls. Haplotypes were constructed after linkage disequilibrium analysis.ResultsThe 1614 C allele and CC genotype were associated with risk of developing ACS (PC = 0.014, OR = 1.37 and PC = 0.006, OR = 1.90, respectively). Based on Hosmer–Lemeshow Goodness of Fit test, the recessive model was selected to estimate risk between ACS patients and controls adjusted by cardiovascular risk factors using a multiple logistic analysis. In this case, the OR adjusted was 1.78 for the 1614 CC genotype (P = 0.023). The analysis of linkage disequilibrium showed one risk haplotype (ACG) and one protective haplotype (AGG) for developing ACS (P = 0.02, OR = 1.5 and P = 0.04, OR = 0.72, respectively).ConclusionThe results suggest that MHC2TA 1614 gene polymorphism could be involved in the risk of developing ACS.