Long-term Outcomes of 100 Transobturator Tape Procedures.

Aim Satisfactory short-term outcomes of transobturator tapes (TOTs) are recognized, yet a lack of long-term data exists. We investigated long-term patient-reported outcomes of TOTs. Methods A retrospective review was performed of 100 female patients post TOT insertion by a single surgeon (2005-2010). Results and postoperative complications were identified. At long-term follow-up, patients completed ICIQ-Short Form, PGI-S and PGI-I questionnaires. Results Mean age was 51.7 years (33-75), mean follow-up 9.4 years (7.25 - 12.75). Clinically, 68/100(68%) had mixed and 32/100(32%) pure stress urinary incontinence (SUI). Short-term cure/significant improvement in SUI was seen in 98/100(98%). Grade >2 Clavien-Dindo complications occurred in 10/100(10%) within 6 months of surgery. Long-term questionnaire response rate was 76/100(76%). 62/76 (81.57%) described current urinary condition as "much" or "very much" "better." No new complications emerged at long-term follow-up. Conclusion TOTs demonstrate high success rates in treatment of SUI, with no late-onset complications identified in our study. Recent concerns surrounding use of polypropylene tapes make reporting of long-term outcomes both desirable and necessary.

'Maths on the move': Effectiveness of physically-active lessons for learning maths and increasing physical activity in primary school students.

OBJECTIVES: This study evaluated the benefit of physically-active lessons for learning maths multiplication-tables. The impact of the intervention on general numeracy, physical activity (PA), aerobic fitness, body mass index (BMI) and school-day moderate to vigorous PA (MVPA) was also assessed. DESIGN: Randomised controlled cross-over trial. METHOD: Year 3 students (n=172, mean age 8.4±0.3 years, 48% male) were recruited from 10 classes across two urban primary schools. Participants were randomly assigned to a seated classroom (Classroom) group or physically-active lessons in the playground (Playground) and crossed over to the alternative condition in the subsequent school term. The 6-week intervention comprised 3×30min sessions/week. Multiplication-tables (teacher-designed test) and general maths (standardised test) were assessed pre- and post-intervention. Aerobic fitness was assessed via the shuttle-run. Pre- to post-intervention change scores were compared for analysis and effect sizes (ES) calculated. Total PA and MVPA were assessed with accelerometers in a subset of participants. RESULTS: Multiplication scores improved significantly more in Playground than Classroom groups (ES=0.23; p=0.045), while no significant differences were observed in general numeracy (ES=0.05; p=0.66). Total PA and MVPA were substantially higher during Playground than Classroom lessons (ES: total PA=7.4, MVPA=6.5; p<0.001) but there were no differences in PA/MVPA between the groups throughout the rest of the school day. Aerobic fitness improved more in Playground than Classroom groups (ES=0.3; p<0.001) while the change in BMI was not different between groups (p=0.39). CONCLUSIONS: Physically-active lessons may benefit the learning of maths multiplication-tables while favourably contributing to school-day PA/MVPA.

Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity.

Correct wiring in the neocortex requires that responses to an individual guidance cue vary among neurons in the same location, and within the same neuron over time. Nestin is an atypical intermediate filament expressed strongly in neural progenitors and is thus used widely as a progenitor marker. Here we show a subpopulation of embryonic cortical neurons that transiently express nestin in their axons. Nestin expression is thus not restricted to neural progenitors, but persists for 2-3 d at lower levels in newborn neurons. We found that nestin-expressing neurons have smaller growth cones, suggesting that nestin affects cytoskeletal dynamics. Nestin, unlike other intermediate filament subtypes, regulates cdk5 kinase by binding the cdk5 activator p35. Cdk5 activity is induced by the repulsive guidance cue Semaphorin3a (Sema3a), leading to axonal growth cone collapse in vitro. Therefore, we tested whether nestin-expressing neurons showed altered responses to Sema3a. We find that nestin-expressing newborn neurons are more sensitive to Sema3a in a roscovitine-sensitive manner, whereas nestin knockdown results in lowered sensitivity to Sema3a. We propose that nestin functions in immature neurons to modulate cdk5 downstream of the Sema3a response. Thus, the transient expression of nestin could allow temporal and/or spatial modulation of a neuron's response to Sema3a, particularly during early axon guidance.

A binational registry of adults with pulmonary arterial hypertension complicating congenital heart disease.

BACKGROUND: The management of children with congenital heart disease (CHD) has improved over recent decades and several patients surviving with CHD into adulthood are increasing. In developed countries, there are now as many adults as there are children living with CHD. Pulmonary arterial hypertension (PAH) occurs in ∼ 5% of patients with CHD. AIM: We aimed to understand the characteristics and outcomes of this emerging population. METHODS: We collected data retrospectively and prospectively from 12 contributing centres across Australia and New Zealand (2010-2013). Patients were included if they had been diagnosed with PAH and CHD and had been seen once in an adult centre after 1 January 2000. RESULTS: Of 360 patients with CHD-PAH, 60% were female and 90% were New York Heart Association functional class II or III at the time of adult diagnosis of PAH. Mean age at diagnosis of PAH in adulthood was 31.2 ± 14 years, and on average, patients were diagnosed with PAH 6 years after symptom onset. All-cause mortality was 12% at 5 years, 21% at 10 years and 31% at 15 years. One hundred and six patients (30%) experienced 247 hospitalisations during 2936 patient years of follow up. Eighty-nine per cent of patients were prescribed PAH specific therapy (mean exposure of 4.0 years). CONCLUSIONS: Adults with PAH and CHD often have this diagnosis made after significant delay, and have substantial medium-term morbidity and mortality. This suggests a need for children transitioning to adult care with CHD to be closely monitored for this complication.

Hysterectomy, endometrial ablation and Mirena® for heavy menstrual bleeding: a systematic review of clinical effectiveness and cost-effectiveness analysis.

OBJECTIVE: The aim of this project was to determine the clinical effectiveness and cost-effectiveness of hysterectomy, first- and second-generation endometrial ablation (EA), and Mirena® (Bayer Healthcare Pharmaceuticals, Pittsburgh, PA, USA) for the treatment of heavy menstrual bleeding. DESIGN: Individual patient data (IPD) meta-analysis of existing randomised controlled trials to determine the short- to medium-term effects of hysterectomy, EA and Mirena. A population-based retrospective cohort study based on record linkage to investigate the long-term effects of ablative techniques and hysterectomy in terms of failure rates and complications. Cost-effectiveness analysis of hysterectomy versus first- and second-generation ablative techniques and Mirena. SETTING: Data from women treated for heavy menstrual bleeding were obtained from national and international trials. Scottish national data were obtained from the Scottish Information Services Division. PARTICIPANTS: Women who were undergoing treatment for heavy menstrual bleeding were included. INTERVENTIONS: Hysterectomy, first- and second-generation EA, and Mirena. MAIN OUTCOME MEASURES: Satisfaction, recurrence of symptoms, further surgery and costs. RESULTS: Data from randomised trials indicated that at 12 months more women were dissatisfied with first-generation EA than hysterectomy [odds ratio (OR): 2.46, 95% confidence interval (CI) 1.54 to 3.93; p = 0.0002), but hospital stay [WMD (weighted mean difference) 3.0 days, 95% CI 2.9 to 3.1 days; p < 0.00001] and time to resumption of normal activities (WMD 5.2 days, 95% CI 4.7 to 5.7 days; p < 0.00001) were longer for hysterectomy. Unsatisfactory outcomes associated with first- and second-generation techniques were comparable [12.2% (123/1006) vs 10.6% (110/1034); OR 1.20, 95% CI 0.88 to 1.62; p = 0.2). Rates of dissatisfaction with Mirena and second-generation EA were similar [18.1% (17/94) vs 22.5% (23/102); OR 0.76, 95% CI 0.38 to 1.53; p = 0.4]. Indirect estimates suggested that hysterectomy was also preferable to second-generation EA (OR 2.32, 95% CI 1.27 to 4.24; p = 0.006) in terms of patient dissatisfaction. The evidence to suggest that hysterectomy is preferable to Mirena was weaker (OR 2.22, 95% CI 0.94 to 5.29; p = 0.07). In women treated by EA or hysterectomy and followed up for a median [interquartile range (IQR)] duration of 6.2 (2.7-10.8) and 11.6 (7.9-14.8) years, respectively, 962/11,299 (8.5%) women originally treated by EA underwent further gynaecological surgery. While the risk of adnexal surgery was similar in both groups [adjusted hazards ratio 0.80 (95% CI 0.56 to 1.15)], women who had undergone ablation were less likely to need pelvic floor repair [adjusted hazards ratio 0.62 (95% CI 0.50 to 0.77)] and tension-free vaginal tape surgery for stress urinary incontinence [adjusted hazards ratio 0.55 (95% CI 0.41 to 0.74)]. Abdominal hysterectomy led to a lower chance of pelvic floor repair surgery [hazards ratio 0.54 (95% CI 0.45 to 0.64)] than vaginal hysterectomy. The incidence of endometrial cancer following EA was 0.02%. Hysterectomy was the most cost-effective treatment. It dominated first-generation EA and, although more expensive, produced more quality-adjusted life-years (QALYs) than second-generation EA and Mirena. The incremental cost-effectiveness ratios for hysterectomy compared with Mirena and hysterectomy compared with second-generation ablation were £1440 per additional QALY and £970 per additional QALY, respectively. CONCLUSIONS: Despite longer hospital stay and time to resumption of normal activities, more women were satisfied after hysterectomy than after EA. The few data available suggest that Mirena is potentially cheaper and more effective than first-generation ablation techniques, with rates of satisfaction that are similar to second-generation techniques. Owing to a paucity of trials, there is limited evidence to suggest that hysterectomy is preferable to Mirena. The risk of pelvic floor surgery is higher in women treated by hysterectomy than by ablation. Although the most cost-effective strategy, hysterectomy may not be considered an initial option owing to its invasive nature and higher risk of complications. Future research should focus on evaluation of the clinical effectivesness and cost-effectiveness of the best second-generation EA technique under local anaesthetic versus Mirena and types of hysterectomy such as laparoscopic supracervical hysterectomy versus conventional hysterectomy and second-generation EA. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Hysterectomy, endometrial destruction, and levonorgestrel releasing intrauterine system (Mirena) for heavy menstrual bleeding: systematic review and meta-analysis of data from individual patients.

OBJECTIVE: To evaluate the relative effectiveness of hysterectomy, endometrial destruction (both "first generation" hysteroscopic and "second generation" non-hysteroscopic techniques), and the levonorgestrel releasing intrauterine system (Mirena) in the treatment of heavy menstrual bleeding. DESIGN: Meta-analysis of data from individual patients, with direct and indirect comparisons made on the primary outcome measure of patients' dissatisfaction. DATA SOURCES: Data were sought from the 30 randomised controlled trials identified after a comprehensive search of the Cochrane Library, Medline, Embase, and CINAHL databases, reference lists, and contact with experts. Raw data were available from 2814 women randomised into 17 trials (seven trials including 1359 women for first v second generation endometrial destruction; six trials including 1042 women for hysterectomy v first generation endometrial destruction; one trial including 236 women for hysterectomy v Mirena; three trials including 177 women for second generation endometrial destruction v Mirena). Eligibility criteria for selecting studies Randomised controlled trials comparing hysterectomy, first and second generation endometrial destruction, and Mirena for women with heavy menstrual bleeding unresponsive to other medical treatment. RESULTS: At around 12 months, more women were dissatisfied with outcome with first generation hysteroscopic techniques than with hysterectomy (13% v 5%; odds ratio 2.46, 95% confidence interval 1.54 to 3.9, P<0.001), but hospital stay (weighted mean difference 3.0 days, 2.9 to 3.1 days, P<0.001) and time to resumption of normal activities (5.2 days, 4.7 to 5.7 days, P<0.001) were longer for hysterectomy. Unsatisfactory outcomes were comparable with first and second generation techniques (odds ratio 1.2, 0.9 to 1.6, P=0.2), although second generation techniques were quicker (weighted mean difference 14.5 minutes, 13.7 to 15.3 minutes, P<0.001) and women recovered sooner (0.48 days, 0.20 to 0.75 days, P<0.001), with fewer procedural complications. Indirect comparison suggested more unsatisfactory outcomes with second generation techniques than with hysterectomy (11% v 5%; odds ratio 2.3, 1.3 to 4.2, P=0.006). Similar estimates were seen when Mirena was indirectly compared with hysterectomy (17% v 5%; odds ratio 2.2, 0.9 to 5.3, P=0.07), although this comparison lacked power because of the limited amount of data available for analysis. CONCLUSIONS: More women are dissatisfied after endometrial destruction than after hysterectomy. Dissatisfaction rates are low after all treatments, and hysterectomy is associated with increased length of stay in hospital and a longer recovery period. Definitive evidence on effectiveness of Mirena compared with more invasive procedures is lacking.

Granulomatous angiitis leading to a pulmonary veno-occlusive disease-like picture.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension characterised by extensive fibrotic occlusion of pulmonary veins. PVOD has a similar insidious presentation to idiopathic pulmonary arterial hypertension but responds poorly to conventional therapies and has a worse prognosis. The current study reports the case of a Caucasian female with a long history of progressive dyspnoea ultimately diagnosed as focal granulomatous venulitis leading to a pulmonary veno-occlusive disease-like pathology. The present study highlights the challenges in diagnosing and treating this condition.

Metabolic and attentional energy costs of interlimb coordination.

The authors investigated metabolic and attentional energy costs as participants (N = 6) practiced in-phase, antiphase, and 90 degrees -phase cycling (order counterbalanced) on independent bicycle ergometers, with resistance (40 W/ergometer) and frequency (40 rpm) held constant. Coordination stabilized and became more accurate for all 3 cycling modes, as shown by measures of relative phase, but that collective variable could not account for other relevant attributes of the multifaceted motor behavior observed across the 3 coordination modes. In-phase and antiphase cycling were similar in stability and accuracy, but antiphase had the lowest metabolic and attentional energy costs. Because both homologous muscle action and perceptually symmetrical oscillations coincided in the in-phase mode, the absence of predominance of the inphase pattern showed that neither of those musculoskeletal and perceptual factors exclusively determined the strongest attractor of the coordination dynamics. Both metabolic and attentional costs declined with practice, consistent with the hypothesis that adaptive motor behavior is guided by sensory information concerning the energy demands of the task. Attentional cost was influenced not only by the information-processing demands of kinematic stability but also by the metabolic energy demands. Metabolic energy cost appeared to be the crucial determinant of the preferred solution for this coordination task.

The metabolic and cognitive energy costs of stabilising a high-energy interlimb coordination task.

Kinematic (relative phase error), metabolic (oxygen consumption, heart rate) and attentional (baseline and cycling reaction times) variables were measured while participants practised a high energy-demanding, intrinsically unstable 90 degrees relative phase coordination pattern on independent bicycle ergometers. The variables were found to be strongly inter-correlated, suggesting a link between emerging performance stability with practice and minimal metabolic and attentional cost. The effects of practice of 90 degrees relative phase coordination on the performance of in-phase (0 degrees-phase) and antiphase (180 degrees-phase) coordination were investigated by measuring the relative phase attractor layouts and recording the metabolic and attentional cost of the three coordination patterns before and after practice. The attentional variables did not differ significantly between coordination patterns and did not change with practice. Before practice, the coordination performance was most accurate and stable for in-phase cycling, with antiphase next and 90 degrees-phase the poorest. However, metabolic cost was lower for antiphase than either in-phase or 90 degrees-phase cycling, and the pre-practice attractor layout deviated from that predicted on the basis of dynamic stability as an attractor state, revealing an attraction to antiphase cycling. After practice of 90 degrees-phase cycling, in-phase cycling remained the most accurate and stable, with 90 degrees-phase next and antiphase the poorest, but antiphase retained the lowest metabolic energy cost. The attractor layout had changed, with new attractors formed at the practised 90 degrees-phase pattern and its symmetrical partner of 270 degrees-phase. Considering both the pre- and post-practice results, attractors were formed at either a low metabolic energy cost but less stable (antiphase) pattern or at a more stable but higher metabolic energy cost (90 degrees-phase) pattern, but in neither case at the most stable and accurate (in-phase) pattern. The results suggest that energetic factors affect coordination dynamics and that coordination modes lower in metabolic energy expenditure may compete with dynamically stable modes.

The influence of cereal and dairy consumption on the Irish diet: implications for developing food-based dietary guidelines.

OBJECTIVES: To estimate the intakes of cereal and dairy products and their contribution to nutrient intakes in men and women from the Republic of Ireland with a view to formulating food-based dietary guidelines. DESIGN: The North/South Ireland Food Consumption Survey established a database of habitual food and drink consumption using a 7-day food diary. From this database all cereal and dairy products from recipes and identifiable sources were identified and a new database was generated from which analysis of the role of cereal and dairy products in the diet was carried out. RESULTS: Almost 100% of the population consumed cereal and dairy products over the course of the survey week. In general, men consumed significantly more cereal and dairy products than did women (P<0.05). Cereal products made an important contribution to the mean daily intakes of energy (26%), protein (21%), fat (13%), carbohydrate (41%), fibre (45%), iron (43%) and folate (27%). Dairy products also contributed largely to the mean daily intakes of energy (11%), protein (14%), fat (17%), calcium (48%), phosphorus (24%) and vitamin A (27%). Analysis of nutrient intakes across tertiles of cereal and dairy consumption showed that high consumers of wholemeal bread, breakfast cereals, reduced-fat milk and yoghurt had lower fat and higher carbohydrate, fibre and micronutrient intakes than low consumers of these foods. CONCLUSIONS: Findings from the present study could be used to develop effective health strategies to implement changes in cereal and dairy consumption that could alter fat, fibre and micronutrient intakes in the diet.

The temporal pattern of the contribution of fat to energy and of food groups to fat at various eating locations: implications for developing food-based dietary guidelines.

OBJECTIVES: To examine the temporal pattern of the number of eating occasions that occurred at home, at work and outside the home, and to examine the contribution of fat to energy and the contribution of 26 food groups to fat at home and outside the home. DESIGN AND SETTING: Food intake data were collected using a 7-day food diary from a random sample of 18-64-year-old adults from the Republic of Ireland (n=958). Respondents recorded the day, time and location of every eating occasion. RESULTS: The number of eating occasions was constant across the days of the week for meals consumed at home, whereas the number of eating occasions increased at weekends for meals outside the home. The contribution of fat to energy approximated the 35% recommendation at home from Monday to Friday, but increased above this on Saturday and Sunday. The contribution of fat to energy outside the home was always above the recommendation. The food groups that contributed most to fat were similar at home and outside the home. These included butter and full-fat spreads, fresh meat, meat products, meat dishes, biscuits, cakes and pastries, whole milk, and chips and processed potatoes. CONCLUSION: The contribution of fat to energy was above the recommendations when eating outside the home, regardless of day of the week. A number of food groups have been identified that contributed most to fat intake outside the home and these might be targeted in developing public health nutrition strategies to reduce fat intake.

The influence of eating location on nutrient intakes in Irish adults: implications for developing food-based dietary guidelines.

OBJECTIVES: To examine the contribution of the food service sector to the nutrient quality of the Irish diet, and to compare intakes at home, work and outside the home ('out') and within the subgroups of the out location (pub, deli, takeaway). DESIGN AND SETTING: Random sample of adults from the Republic of Ireland. Food intake data were collected using a 7-day food diary. Respondents recorded the location of every eating occasion determined by where the food was prepared rather than consumed. RESULTS: Intakes of energy, protein, fat and carbohydrate were significantly greater at home than at work or out (P<0.05). The intake of alcohol was significantly (P<0.001) greater out than at home or work. The percentage contribution of fat to energy was above the recommendations (33% of total energy and 35% of food energy) for both men and women at all locations, with the exception of the contribution of fat to total energy for men at the out location. Within the subgroups of the out location, the contribution of alcohol to total energy was greatest in pubs and the contribution of fat to both total and food energy was greatest in takeaways. Intakes of fibre and most micronutrients per 10 MJ of food energy were greater (P<0.05) at home than at work or out. CONCLUSION: Foods eaten outside the home contribute a disproportionately high level of fat intake and should be targeted in public health nutrition strategies.

Analysis of the temporal intake of cereal and dairy products in Irish adults: implications for developing food-based dietary guidelines.

OBJECTIVES: To analyse the temporal distribution of the intake of cereal and dairy products in the Republic of Ireland. DESIGN: The North/South Ireland Food Consumption Survey established a database of habitual food and drink consumption using a 7-day food diary. The database also recorded the time and day of food consumption. Mean intakes of cereal and dairy products were calculated for time of the day and day of the week. RESULTS: At the weekend, the percentage of consumers decreased for nearly all cereal and dairy products. White bread, total cereals, full-fat milk and total dairy intakes were significantly lower at the weekend (P<0.01) compared with weekdays. Intakes of cereal and dairy products over time of the day showed clear mealtime or snacking patterns when the number of consumers was controlled for. White bread, wholemeal bread, total cereals, full-fat milk, reduced-fat milk and total dairy intakes showed mealtime peaks for morning, afternoon and evening. When examined by tertile of intake, tertile of percentage energy from fat and tertile of fibre intake, intakes of cereal and dairy products over time of the day and day of the week were similar to trends described above, regardless of the tertile. CONCLUSIONS: Temporal analysis of the intakes of cereal and dairy products did not reveal any unusual trends in this population. However, the significant methodological issues raised in this paper will be of benefit to other aspects of research in this area.

The spasticity paradox: movement disorder or disorder of resting limbs?

BACKGROUND: Spasticity is defined/assessed in resting limbs, where increased stretch reflex activity and mechanical joint resistance are evident. Treatment with antispastic agents assumes that these features contribute to the movement disorder, although it is unclear whether they persist during voluntary contraction. OBJECTIVES: To compare reflex amplitude and joint resistance in spastic and normal limbs over an equivalent range of background contraction. METHODS: Thirteen normal and eight hemiparetic subjects with mild/moderate spasticity and without significant contracture were studied. Reflex and passive joint resistance were compared at rest and during six small increments of biceps voluntary contraction, up to 15% of normal maximum. A novel approach was used to match contraction levels between groups. RESULTS: Reflex amplitude and joint mechanical resistance were linearly related to contraction in both groups. The slopes of these relations were not above normal in the spastic subjects on linear regression. Thus, reflex amplitude and joint resistance were not different between groups over a comparable range of contraction levels. Spastic subjects exhibited a smaller range of reflex modulation than normals because of decreased maximal contraction levels (weakness) and significant increases of resting contraction levels. CONCLUSIONS: Spasticity was most evident at rest because subjects could not reduce background contraction to normal. When background contractions were matched to normal levels, no evidence of exaggerated reflex activity or mechanical resistance was found. Instead, reduced capacity to modulate reflex activity dynamically over the normal range may contribute to the movement disorder. This finding does not support the routine use of antispastic agents to treat the movement disorder.

Variation of magnitude and timing of wrist flexor stretch reflex across the full range of voluntary activation.

This paper reports an investigation of the magnitude and timing of the stretch reflex over the full range of activation of flexor carpi radialis. While it is well established that the magnitude of the reflex increases with the level of muscle activation, there have been few studies of reflex magnitude above 50% of maximum voluntary contraction (MVC) and virtually no study of the timing of the response in relation to activation level. Continuous small amplitude (approximately 2 degrees) perturbations were applied to the wrist of 12 normal subjects while they maintained contraction levels between 2.5-95% MVC, monitored via surface electromyography (EMG). Both narrow band (4-5 Hz) and broad band (0-10 Hz) stretch perturbations were employed. The gain (EMG output/stretch input) and phase advance of the reflex varied with the level of muscle activation in a similar manner for both types of stretch, but there were significant differences in the patterns of change due to stretch bandwidth. Consistent with previous studies, the group average reflex gain initially increased with muscle activation level and then saturated. Inspection of individual data, however, revealed that the gain reached a peak at about 60% MVC and then decreased at higher contraction levels, the pattern across the full range of activation being well described by quadratic functions (mean r2=0.82). This quadratic pattern has not been reported previously for the neural reflex response in any muscle but is consistent with the pattern that has been reliably observed in studies of the mechanical reflex response in lower limb muscles. In contrast to the pattern for reflex gain, the phase advance of the reflex (at a stretch frequency of 4.5 Hz) decreased linearly from approximately 130 degrees at the lowest contraction levels to approximately 50 degrees as maximum voluntary contraction was reached (mean r2=0.69). This decrease corresponds to a delay of 49 ms introduced centrally in reflex pathways. All subjects showed clearly defined quadratic functions relating reflex gain and linear functions relating reflex phase to activation level, but there were considerable individual differences in the slopes of these functions which point to systematic differences in synaptic behaviour of the motoneuron pool. Thus, there was wide inter-subject variation in both the contraction level at which the reflex gain reached a peak (31-69% MVC) and the highest target contraction level that could be sustained during reflex measurement (47-95% MVC). A high correlation between these variables (r2=0.78) suggests a linear relation between afferent support of contraction and muscle fatigability. The decline in reflex gain at high levels of muscle activation signals a failure of muscle afferent input and subjects in whom the gain reached a peak and declined early were unable to sustain higher target contraction levels. The results of the study show that both the timing and magnitude of the stretch reflex vary markedly over the full range of voluntary muscle activation. The pattern of variation may account for why the stretch reflex contributes most effectively to muscle mechanics over the lower half of the range of activation, while progressive reductions in both gain and phase advance at higher levels render the reflex mechanically less effective and make tremor more likely.

Differential trafficking of the Niemann-Pick C1 and 2 proteins highlights distinct roles in late endocytic lipid trafficking.

UNLABELLED: The cellular location of Niemann-Pick C2 protein (NPC2) in cultured human fibroblasts and Chinese hamster ovary cells was examined immunocytochemically and in living cells by expression of a functional red fluorescent protein chimeric analogue. RESULTS: NPC2 is present in the lysosomes of both cholesterol-depleted and -replenished cells, unlike Niemann-Pick C1 protein (NPC1) which is recruited to late endosomes only upon uptake of low-density lipoprotein. With mobilization of cholesterol from lysosomes, immunocytochemical detection of NPC2 in lysosomes is greatly diminished, whereas NPC1 remains in the late endosomal compartment. We found a partial overlap in the trafficking and organellar sites of accumulation of NPC2 and NPC1. In living cells, NPC2 traffics with NPC1 in late endosomal tubules. However, in contrast to NPC1, which remains either in late endosomal vesicles and tubules or at the peripheries of cholesterol-laden lysosomes, NPC2 moves into the central core of lysosomes. Glycolipid analysis reveals that, in contrast to null mutant NPC1 cells, which accumulate GM2 ganglioside only at the plasma membrane, with no endocytic storage, absence of NPC2 protein in null mutant NPC2 cells does not block internalization of GM2 into endocytic vesicles. This difference in the cellular distribution of GM2 in NPC1 and NPC2 null mutants is the first report of a variation in the phenotypic expression of these genotypically distinct lesions. CONCLUSION: We speculate that while NPC1 may play a major role in the sorting of glycolipids as well as cholesterol within the late endosomes, NPC2 primarily plays a role in the egress of cholesterol and, potentially, glycolipids from lysosomes. These proteins appear not to be integrated into a tightly bound biological complex, but rather represent separate functional entities that complement each other.

Practice effects on coordination and control, metabolic energy expenditure, and muscle activation.

One defining characteristic of skilled motor performance is the ability to complete the task with minimum energy expenditure. This experiment was designed to examine practice effects on coordination and control, metabolic energy expenditure, and muscle activation. Participants rowed an ergometer at 100 W for ten 16-min sessions. Oxygen consumption and perceived exertion (central and peripheral) declined significantly with practice and movement economy improved (reliably) by 9%. There was an associated but non-significant reduction in heart rate. Stroke rate decreased significantly. Peak forces applied to the ergometer handle were significantly less variable following practice and increased stability of the post-practice movement pattern was also revealed in more tightly clustered plots of hip velocity against horizontal displacement. Over practice trials muscle activation decreased, as revealed in integrated EMG data from the vastus lateralis and biceps brachii, and coherence analysis revealed the muscle activation patterns became more tightly coordinated. The results showed that practice reduced the metabolic energy cost of performance and practice-related refinements to coordination and control were also associated with significant reductions in muscle activation.

Coordination of the ankle joint complex during walking.

A simple model of the joint between the leg and the rearfoot is that of two hinges each with one degree of freedom. The superior hinge at the talocrural joint caters for most of the sagittal plane motion due to its mediolateral orientation. Motion in the transverse and coronal planes is largely taken up by the subtalar joint which has an inclination of 42 degrees to the transverse plane and deviates 23 degrees to the medial side. It could be expected from the orientation of this joint that rearfoot motion in the coronal plane (inversion/eversion) would be tightly coupled to motion in the transverse plane (adduction/abduction). A simple, non-viscous mechanical hinge joint would produce an in-phase, fixed gain relationship between inversion/eversion and adduction/abduction. This relation could be adequately quantified by Pearson's product moment correlation (r(P)). In contrast, muscular control of the joint, which introduces visco-elastic elements and time-delayed control lines and feedback loops, could be characterised by more complex phase and gain relations among the frequency components of the signals. These relations can be characterised by a transfer function relation (gain and phase angle) computed using a dynamic analysis. In the present study, both Pearson's correlation and linear systems analysis were employed. For 43 normal adults, five trials of one walking stride (stance and swing phases) were videographed at 30 Hz with three markers placed on each of the leg and rearfoot. Using inversion/eversion as the input and adduction/abduction as the output, the proportion of the total variance accounted for by a dynamic relation was measured by the coherence square function, which is analogous to the correlation squared (r(P)(2)). The mean r(P)(2) was 0.26, whereas the mean overall coherence was 0.62, thus accounting for more than twice the variance. This result suggests that while there may be a degree of simple mechanical coupling between inversion/eversion and adduction/abduction during walking, the major control is via muscular and/or visco-elastic passive elements.