Antibody to the Filarial Antigen Wb123 Reflects Reduced Transmission and Decreased Exposure in Children Born following Single Mass Drug Administration (MDA)

Background

Antibody (Ab) to the Wuchereria bancrofti (Wb) infective larval (L3) antigen Wb123, using a Luciferase Immunoprecipitation System (LIPS) assay, has been shown to be a species-specific, early marker of infection developed for potential use as a surveillance tool following transmission interruption post mass drug administration. To examine its usefulness in a single filarial-endemic island assessed at two time points with markedly different levels of transmission, Ab to Wb123 was measured in sera collected from subjects from Mauke, Cook Islands in 1975 (no previous treatment) and 1992 (5 years after a one time island-wide treatment with diethylcarbamazine [DEC]).

Findings

Between 1975 and 1992, Wb transmission decreased dramatically as evidenced by reduced prevalences of microfilariae (31% vs. 5%) and circulating Ag (CAg, 49% vs. 16%). Age specific prevalence analysis showed a dramatic reduction in Wb123 Ab positivity from 54% (25/46) in 1975 to 8% (3/38) in 1992 in children 1–5 years (p<0.0001), reflecting the effects of single-dose treatment five years earlier. By 1992, Wb123 Ab prevalence in children 6–10 years had fallen from 75% (42/56) in 1975 to 42% (33/79) consistent with a lower cumulative transmission potential. In the whole population, Wb123 seropositivity decreased from 86% to 60% between 1975 and 1992. In CAg+ subjects the levels of Wb123 Ab were indistinguishable between the 2 time points but differed in those who were CAg− (p<0.0001). In paired sample analysis, individuals who were CAg+ in 1975 but became CAg− in 1992 had significantly lower Ab levels in 1992 (p<0.0001), with 9/40 (23%) becoming seronegative for Wb123.

Conclusions

The relationship between reduction in Wb123 Ab prevalence and the reduction of transmission, seen most clearly in young children, strongly advocates for the continuing assessment and rapid development of Wb123 as a surveillance tool to detect potential transmission of bancroftian filariasis in treated endemic areas.     

Improved beta-cell function after standardized weight reduction in severely obese subjects

Islet function was examined in 13 severely obese women [body mass index 46.4 +/- 5.5 (SD) kg/m(2)] before and after standardized 15 and 25% weight reduction (WR) instituted by bariatric surgery. The insulin response to arginine at fasting (AIR(1)), at 14 mmol/l, and at >25 mmol/l glucose was reduced by 37-50% after 15 and 25% WR (P 相似文献   

Effects on the crank torque profile when changing pedalling cadence in level ground and uphill road cycling

Despite the importance of uphill cycling performance during cycling competitions, there is very little research investigating uphill cycling, particularly concerning field studies. The lack of research is partly due to the difficulties in obtaining data in the field. The aim of this study was to analyse the crank torque in road cycling on level and uphill using different pedalling cadences in the seated position. Seven male cyclists performed four tests in the seated position (1) on level ground at 80 and 100 rpm, and (2) on uphill road cycling (9.25% grade) at 60 and 80 rpm.The cyclists exercised for 1 min at their maximal aerobic power. The bicycle was equipped with the SRM Training System (Schoberer, Germany) for the measurement of power output (W), torque (Nm), pedalling cadence (rpm), and cycling velocity (km h(-1)). The most important finding of this study indicated that at maximal aerobic power the crank torque profile (relationship between torque and crank angle) varied substantially according to the pedalling cadence and with a minor effect according to the terrain. At the same power output and pedalling cadence (80 rpm) the torque at a 45 degrees crank angle tended (p < 0.06) to be higher (+26%) during uphill cycling compared to level cycling. During uphill cycling at 60 rpm the peak torque was increased by 42% compared with level ground cycling at 100 rpm.When the pedalling cadence was modified, most of the variations in the crank torque profile were localised in the power output sector (45 degrees to 135 degrees).     

Quadriceps neuromuscular function and self-reported functional ability in knee osteoarthritis

The purposes of this study were to determine 1) the relationships of self-reported function scores in patients with knee osteoarthritis (OA) to both maximal isometric torque and to isotonic power at a variety of loads, and 2) the degree to which muscle volume (MV) or voluntary activation (VA) are associated with torque and power measures in this population. Isometric maximal voluntary contraction (MVC) torque and isotonic power [performed at loads corresponding to 10, 20, 30, 40, and 50% MVC, and a minimal load ("Zero Load")] were measured in 40 participants with knee OA. Functional ability was measured with the Western Ontario and McMaster Osteoarthritis Index (WOMAC) function subscale. MV was determined with magnetic resonance imaging, and VA was measured with the interpolated twitch technique. In general, power measured at lower loads (Zero Load and 10-30% MVC, r(2) = 0.21-0.28, P < 0.05) predicted a greater proportion of the variance in function than MVC torque (r(2) = 0.18, P < 0.05), with power measured at Zero Load showing the strongest association (r(2) = 0. 28, P < 0.05). MV was the strongest predictor of MVC torque and power measures in multiple regression models (r(2) = 0.42-0.72). VA explained only 6% of the variance in MVC torque and was not significantly associated with power at any load (P > 0.05). Quadriceps MVC torque and power are associated with self-reported function in knee OA, but muscle power at lower loads is more predictive of function than MVC torque. The variance in MVC torque and power between participants is due predominantly to differences in MV and has little to do with deficits in VA.     

Oxygen-dependent protection of radiation lung damage in mice by WR 2721

The modification of early and late radiation damage to the mouse lung by oxygen and WR 2721 has been studied by measurement of breathing rate, lethality, pleural fluid and hydroxyproline content. Protection by hypoxia and sensitization by hyperoxia of early radiation pneumonitis were demonstrated. There was a tendency for the protective effect of WR 2721 to decrease as the breathed oxygen concentration was raised above normal levels. WR 2721 protection of the late damage was higher (PF = 1.6-1.65) than was seen for early pneumonitis (PF = 1.3-1.35) when either breathing rate or lethality were used. Protection factors (PF) gained from measurements of pleural fluid at a year after treatment were similar to those for other endpoints of late damage (PF = 1.7). In contrast, the measurement of fibrosis through determination of lung hydroxyproline at 1 year gave a somewhat lower protection factor for WR 2721. In the same experiments the degree of epilation on the dorsal thorax was scored at 6 weeks. One hundred per cent oxygen gave enhancement (dose enhancement factor (DEF) = 1.2), 9 per cent oxygen reduced damage (DEF less than 0.7) and WR 2721 gave PF values in excess of 1.4 at all oxygen concentrations used. This showed that the radiation response of hair follicles was more sensitive to WR 2721 or to changes of oxygen than the lung. The results presented indicate a competitive interaction between WR 2721 and oxygen for the same injury site causing a shift in the oxygen K curve to higher oxygen concentrations. The validity of applying functional or survival measurements to assess the extent of pulmonary fibrosis is discussed.     

The effects of antagonist prefatigue on agonist torque and electromyography

This study assessed the effects of hamstring prefatigue on peak torque, peak power, time to peak torque, knee angle of peak torque, and electromyography (EMG) activity of the hamstrings and quadriceps group during knee extensions at angular velocities of 60 degrees, 180 degrees, and 300 degrees.s(-1). Twenty Division I wrestlers performed 5 maximal knee extensions in prefatigued and nonfatigued conditions of the hamstring group. This study demonstrated that when the hamstrings were prefatigued, the quadriceps produced significant decreases in peak torque of 1.7% (p < 0.05), peak power of 11% (p < 0.05), and rate to peak torque of 6.4% (p < 0.01) as compared with the nonfatigued state. When the hamstrings were prefatigued, they produced a 25% greater amount of EMG activity during knee extension (p < 0.01) than when not prefatigued. There was no significant difference in quadriceps EMG activity whether the hamstring group was prefatigued or not (p > 0.05). The decrease in quadriceps peak torque during the prefatigued condition was more pronounced (p < 0.01) at an angular velocity of 60 degrees.s(-1) than at 180 degrees or 300 degrees.s(-1). In other words, prefatiguing the antagonist appears to be most detrimental to torque output of the quadriceps in the condition that most closely replicates the speed at which "isotonic" weight training occurs (60 degrees.s(-1)) and suggests a limitation to agonist-antagonist superset training.     

Mechanomyographic and electromyographic responses during submaximal to maximal eccentric isokinetic muscle actions of the biceps brachii

The purpose of this investigation was to determine the mechanomyography (MMG) and electromyography (EMG) amplitude and mean power frequency (MPF) vs. eccentric isokinetic torque relationships for the biceps brachii muscle. Nine adults (mean +/- SD age = 23.1 +/- 2.9 years) performed submaximal to maximal eccentric isokinetic muscle actions of the dominant forearm flexors. After determination of isokinetic peak torque (PT), the subjects randomly performed submaximal step muscle actions in 10% increments from 10 to 90% PT. Polynomial regression analyses indicated that the MMG amplitude vs. eccentric isokinetic torque relationship was best fit with a quadratic model (R(2) = 0.951), where MMG amplitude increased from 10 to 60% PT and then plateaued from 60 to 100% PT. There were linear increases in MMG MPF (r(2) = 0.751) and EMG amplitude (r(2) = 0.988) with increases in eccentric isokinetic torque, but there was no significant change in EMG MPF from 10 to 100% PT. The results suggested that for the biceps brachii, eccentric isokinetic torque was increased to approximately 60% PT through concurrent modulation of the number of active motor units and their firing rates, whereas additional torque above 60% PT was produced only by increases in firing rates. These findings contribute to current knowledge of motor-control strategies during eccentric isokinetic muscle actions and could be useful in the design of training programs.     

Identification of a Vo2 deflection point coinciding with the heart rate deflection point and ventilatory threshold in cycling

The purposes of this study were to compare the patterns of the work rate (WR)-Vo2 and WR-heart rate (HR) relationships in incremental cycling, to ascertain the occurrence of a Vo2 deflection (Vo2def) coinciding with the HR deflection point (HRdef ), and to determine whether the Vo2def, if present, coincides with the ventilatory anaerobic threshold (VT). Twenty-four professional cyclists performed a maximal incremental test on a wind-load cycle ergometer. Work rate, HR, Vo2, and Vco2 were recorded. The WR-Vo2 relationships obtained were linear up to submaximal WR and curvilinear thereafter and thus described a Vo2def. The WR and Vo2 at Vo2def were mathematically determined for all subjects. The ratio of DeltaWR.DeltaVo2 up to Vo2def was significantly lower than that above Vo2def (90 +/- 11 W.L.min versus 133 +/- 35 W.L.min, p < 0.0001). The WR-HR relationships obtained were linear up to submaximal WR and curvilinear thereafter. The WR and HR at HRdef were mathematically determined for all subjects. The WR values at Vo2def and at HRdef (329 +/- 32 W and 326 +/- 34 W) were significantly correlated (R = 0.96, p < 0.0001) and in good concordance (limits of agreement from -4.7% to 3.2%, Bland-Altman analysis). The Vo2 at VT was then determined for all subjects. The Vo2 values at Vo2def and at VT were significantly correlated (R = 0.99, p < 0.0001) and in strong concordance (limits of agreement from -1.9% to 1.0%, Bland-Altman analysis). In conclusion, a Vo2def coinciding with HRdef and VT was shown. This confirms that the determination of the WR-HR relationship and of HRdef is a practical and noninvasive means of identifying anaerobic threshold.     

Energetics of actively powered locomotion using the simplest walking model

We modified an irreducibly simple model of passive dynamic walking to walk on level ground, and used it to study the energetics of walking and the preferred relationship between speed and step length in humans. Powered walking was explored using an impulse applied at toe-off immediately before heel strike, and a torque applied on the stance leg. Although both methods can supply energy through mechanical work on the center of mass, the toe-off impulse is four times less costly because it decreases the collision loss at heel strike. We also studied the use of a hip torque on the swing leg that tunes its frequency but adds no propulsive energy to gait. This spring-like actuation can further reduce the collision loss at heel strike, improving walking energetics. An idealized model yields a set of simple power laws relating the toe-off impulses and effective spring constant to the speed and step length of the corresponding gait. Simulations incorporating nonlinear equations of motion and more realistic inertial parameters show that these power laws apply to more complex models as well.     

Ets-1 is essential for connective tissue growth factor (CTGF/CCN2) induction by TGF-β1 in osteoblasts

Background

Ets-1 controls osteoblast differentiation and bone development; however, its downstream mechanism of action in osteoblasts remains largely undetermined. CCN2 acts as an anabolic growth factor to regulate osteoblast differentiation and function. CCN2 is induced by TGF-β1 and acts as a mediator of TGF-β1 induced matrix production in osteoblasts; however, the molecular mechanisms that control CCN2 induction are poorly understood. In this study, we investigated the role of Ets-1 for CCN2 induction by TGF-β1 in primary osteoblasts.

Results

We demonstrated that Ets-1 is expressed and induced by TGF-β1 treatment in osteoblasts, and that Ets-1 over-expression induces CCN2 protein expression and promoter activity at a level similar to TGF-β1 treatment alone. Additionally, we found that simultaneous Ets-1 over-expression and TGF-β1 treatment synergize to enhance CCN2 induction, and that CCN2 induction by TGF-β1 treatment was impaired using Ets-1 siRNA, demonstrating the requirement of Ets-1 for CCN2 induction by TGF-β1. Site-directed mutagenesis of eight putative Ets-1 motifs (EBE) in the CCN2 promoter demonstrated that specific EBE sites are required for CCN2 induction, and that mutation of EBE sites in closer proximity to TRE or SBE (two sites previously shown to regulate CCN2 induction by TGF-β1) had a greater effect on CCN2 induction, suggesting potential synergetic interaction among these sites for CCN2 induction. In addition, mutation of EBE sites prevented protein complex binding, and this protein complex formation was also inhibited by addition of Ets-1 antibody or Smad 3 antibody, demonstrating that protein binding to EBE motifs as a result of TGF-β1 treatment require synergy between Ets-1 and Smad 3.

Conclusions

This study demonstrates that Ets-1 is an essential downstream signaling component for CCN2 induction by TGF-β1 in osteoblasts, and that specific EBE sites in the CCN2 promoter are required for CCN2 promoter transactivation in osteoblasts.     

Longitudinal evaluation of aerobic capacity determined by torque auto-controlled system with the feedback of photoelectric pulse

We have previously developed a unique and simple procedure for assessing cardiorespiratory fitness. The present investigation was conducted to evaluate whether an aerobic index determined by torque auto-controlled system with the feedback of photoelectric pulse could sufficiently approximate the cardiorespiratory fitness represented by anaerobic threshold (AT) and maximal oxygen uptake (VO2max). Analysis of the cross-sectional data indicated that the aerobic score (AS: K (WR/Wt)/HR; where WR = mean work rate during 12-min cycling, Wt = weight, and HR = mean heart rate during 12-min cycling) determined by the torque auto-controlled system was significantly correlated with directly measured VO2/AT (r = 0.922, 76 males; r = 0.814, 34 females). Cross-validity of the predicted VO2max from the AS was significant and sufficiently high (r = 0.949, 31 males) for use in the general public. In addition, the effects of cycling or jogging training on the AS were longitudinally investigated on 17 females and 1 male. Major effects of the training were significant improvements in the AS, VO2max, and VO2/AT. Delta percentage change [(post-value - pre-value)/pre-value; delta %] in the AS was closely associated (r = 0.718, 8 females) with delta % in VO2/AT. It appears likely from the present investigation that information obtained through the use of our unique system (i.e., the AS) could provide considerably reliable estimate of cardiorespiratory fitness in both males and females.     

Effect of reduced impulse activity on the development of identified motor terminals in Drosophila larvae

In Drosophila larvae, motoneurons show distinctive differences in the size of their synaptic boutons; that is, axon 1 has type Ib ("big" boutons) terminals and axon 2 has type Is ("small" boutons) terminals on muscle fibers 6 and 7. To determine whether axon 1 develops large boutons due to its high impulse activity, we reduced impulse activity and examined the motor terminals formed by axon 1. The number of functional Na(+) channels was reduced either with the nap(ts) mutation or by adding tetrodotoxin (TTX) to the media (0.1 microg/g). In both cases, the rate of locomotion was decreased by approximately 40%, presumably reflecting a decrease in impulse activity. Locomotor activity was restored to above wild-type (Canton-S) levels when nap(ts) was combined with a duplication of para, the Na(+)-channel gene. Lucifer yellow was injected into the axon 1 motor terminals, and we measured motor terminal area, length, the number of branches, and the number and width of synaptic boutons. Although all parameters were smaller in nap(ts) and TTX-treated larvae compared to wild-type, most of these differences were not significant when the differences in muscle fiber size were factored out. Only bouton width was significantly smaller in both different nap(ts) and TTX-treated larvae: boutons were about 20% smaller in nap(ts) and TTX-treated larvae, and 20% larger in nap(ts); Dp para(+) compared to wild-type. In addition, terminal area was significantly smaller in nap(ts) compared to wild-type. Bouton size at Ib terminals with reduced impulse activity was similar to that normally seen at Is terminals. Thus, differences in impulse activity play a major role in the differentiation of bouton size at Drosophila motor terminals.     

Enhanced running wheel activity of both Mch1r- and Pmch-deficient mice

Mch1r-deficient (Mch1r(-/-)) mice are hyperphagic, hyperactive, lean, and resistant to diet-induced obesity. To examine whether the MCH1R is involved in regulating activity-based energy expenditure, we investigated voluntary wheel running (WR) activity of wild-type (WT) and Mch1r(-/-) mice basally, in response to diets with different caloric density and with different feeding schedules. We also evaluated WR activity of mice with ablation of the prepro-MCH gene (Pmch(-/-) mice). Dark cycle WR activity of Mch1r(-/-) mice fed low fat (LF) chow was increased significantly relative to WT mice. Transition to moderate high-fat (MHF) diet was associated with an increase in nocturnal WR activity in both genotypes. Both Mch1r(-/-) and WT mice exhibited food anticipatory activity (FAA) before the daily scheduled feeding time, indicating that MCH1R is not required for FAA. Naloxone (3 mg/kg, i.p.) suppressed WR activity of both genotypes, suggesting opioid regulation of locomotor activity. WR increased nocturnal dynorphin mRNA levels in Mch1r(-/-) brain. Importantly, Pmch-deficient mice had significantly enhanced WR activity relative to WT controls. These results suggest that endogenous MCH plays an inhibitory role in regulating locomotor activity. In summary, we demonstrated enhanced WR activities in mice lacking either MCH or its cognate receptor.     

Developmental orthopaedic disease in limbs of foals: between-breed variations in the prevalence, location and severity at weaning

Developmental orthopaedic disease (DOD) affects all breeds and is a common cause of pain and lameness for horses in sports. A thorough knowledge of between-breed variations for the prevalence of DOD, for its distribution among the various joints and for its severity at earlier stages in the disease process is needed in order to improve the relevance and the cost-effectiveness of DOD screening protocols. However, no prevalence study for DOD simultaneously performed on several breeds with similar farming systems and based on radiographic findings (RF) on quite a large number of joints and views, has been reported earlier. The objective of this study was to describe variations in the prevalence, location and severity of DOD in foals at weaning among Warmbloods (Wb), Standardbreds (St) and Thoroughbreds (Tb) with similar farming systems. DOD assessment was based on RF on the limb joints. A total of 392 foals from 21 volunteer stud farmers were included. To determine the statuses of foals regarding DOD, they were X-rayed on the front- and hind-limb digit, carpus, hock and stifle joints. X-ray data were analysed by three experienced equine veterinarians who gave a common assessment about the entity and the severity of RF. Between-breed variations were analysed in two steps: the first implemented for each anatomical site; the second considered only foals affected by DOD to explore RF association patterns on the affected sites, at foal level. The three breeds were represented by 25.0% of Wb, 41.1% of St and 33.9% of Tb. DOD was present in 66.3% of the foals (95% confidence interval (CI) = 61.6% to 71.0%). Prevalence of foals affected by DOD and distribution of the RF severity score on the anatomical sites differed depending on the breed: Wb foals seemed to be the most affected by DOD. Cluster analyses showed no clear association among sites. However, Wb and Tb foals were preferentially classified together because they were affected on the same sites, whereas St foals were distributed in other classes. The most severely affected sites were the proximal part of the hock and the femoro-patellar joint for Wb and St foals, and the fore fetlock and the distal part of the hock for Tb foals. This is the first epidemiological study reporting between-breed variations in DOD distribution and severity, for the limb joints of foals. These results contribute to broaden the knowledge on DOD and are of great interest to improve detection of DOD within a particular breed.