Glutamine repeat variants in human RUNX2 associated with decreased femoral neck BMD, broadband ultrasound attenuation and target gene transactivation

RUNX2 is an essential transcription factor required for skeletal development and cartilage formation. Haploinsufficiency of RUNX2 leads to cleidocranial displaysia (CCD) a skeletal disorder characterised by gross dysgenesis of bones particularly those derived from intramembranous bone formation. A notable feature of the RUNX2 protein is the polyglutamine and polyalanine (23Q/17A) domain coded by a repeat sequence. Since none of the known mutations causing CCD characterised to date map in the glutamine repeat region, we hypothesised that Q-repeat mutations may be related to a more subtle bone phenotype. We screened subjects derived from four normal populations for Q-repeat variants. A total of 22 subjects were identified who were heterozygous for a wild type allele and a Q-repeat variant allele: (15Q, 16Q, 18Q and 30Q). Although not every subject had data for all measures, Q-repeat variants had a significant deficit in BMD with an average decrease of 0.7SD measured over 12 BMD-related parameters (p = 0.005). Femoral neck BMD was measured in all subjects (−0.6SD, p = 0.0007). The transactivation function of RUNX2 was determined for 16Q and 30Q alleles using a reporter gene assay. 16Q and 30Q alleles displayed significantly lower transactivation function compared to wild type (23Q). Our analysis has identified novel Q-repeat mutations that occur at a collective frequency of about 0.4%. These mutations significantly alter BMD and display impaired transactivation function, introducing a new class of functionally relevant RUNX2 mutants.

Vibration or balance training on neuromuscular performance in osteopenic women

Maintaining neuromuscular function in older age is an important topic for aging societies, especially for older women with low bone density who may be at risk of falls and bone fracture. This randomized controlled trial investigated the effect of resistive exercise with either whole-body vibration training (VIB) or coordination/balance training (BAL) on neuromuscular function (countermovement jump, multiple 1-leg hopping, sit-to-stand test). 68 postmenopausal women with osteopenia or osteoporosis were recruited for the study. 57 subjects completed the 9-month, twice weekly, intervention period. All subjects conducted 30 min of resistance exercise each training day. The VIB-group performed additional training on the Galileo vibration exercise device. The BAL-group performed balance training. An "intent-to-treat" analysis showed greater improvement in the VIB-group for peak countermovement power (p=0.004). The mean [95% confidence interval] effect size for this parameter was a  + 0.9[0.3 to 1.5] W/kg greater change in VIB than BAL after 9 months. In multiple 1-leg hopping, a significantly better performance in the VIB-group after the intervention period was seen on a "per-protocol" analysis only. Both groups improved in the sit-to-stand test. The current study provides evidence that short-duration whole-body vibration exercise can have a greater impact on some aspects of neuromuscular function in post-menopausal women with low bone density than proprioceptive training.

Morphometric vertebral fractures of the lower thoracic and lumbar spine, physical function and quality of life in men

The epidemiology and sequelae of morphometric vertebral fracture (MVF) are poorly documented. We found that MVFs of the lower thoracic and lumbar spine were associated with poor quality of life and impaired physical function in men. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry.

Changes in lower extremity muscle function after 56 days of bed rest

Preservation of muscle function, known to decline in microgravity and simulation (bed rest), is important for successful spaceflight missions. Hence, there is great interest in developing interventions to prevent muscle-function loss. In this study, 20 males underwent 56 days of bed rest. Ten volunteers were randomized to do resistive vibration exercise (RVE). The other 10 served as controls. RVE consisted of muscle contractions against resistance and concurrent whole-body vibration. Main outcome parameters were maximal isometric plantar-flexion force (IPFF), electromyography (EMG)/force ratio, as well as jumping power and height. Measurements were obtained before and after bed rest, including a morning and evening assessment on the first day of recovery from bed rest. IPFF (-17.1%), jumping peak power (-24.1%), and height (-28.5%) declined (P < 0.05) in the control group. There was a trend to EMG/force ratio decrease (-20%; P = 0.051). RVE preserved IPFF and mitigated the decline of countermovement jump performance (peak power -12.2%; height -14.2%). In both groups, IPFF was reduced between the two measurements of the first day of reambulation. This study indicates that bed rest and countermeasure exercises differentially affect the various functions of skeletal muscle. Moreover, the time course during recovery needs to be considered more thoroughly in future studies, as IPFF declined not only with bed rest but also within the first day of reambulation. RVE was effective in maintaining IPFF but only mitigated the decline in jumping performance. More research is needed to develop countermeasures that maintain muscle strength as well as other muscle functions including power.

Is nine weeks of complex training effective for improving lower body strength, explosive muscle function, sprint and jumping performance?

There is currently minimal evidence from training studies that document the effectiveness of complex training to elicitgains in explosive muscle function that are greater than those obtained from a more conventional approach. Over nineweeks of training, 20 recreationally trained athletes with a minimum of one year of resistance training experience wererandomly assigned to either a complex training group (n¼9) or a conventional training group (n¼11). In an attempt tocapitalise on muscle’s post-activation potentiation response, the complex training group performed all sets of ½ backsquats prior to sets of jumps squats, while the conventional training group performed jump squats prior to sets of ½ backsquats. Lower body explosive muscle function and jump performance improved significantly in both groups. The complextraining group’s improvement in running vertical jump performance was significantly greater than in the conventionalgroups. Sprint performance was not significantly improved in either training group.

The relationship between lower body strength and obstructed gait in community-dwelling older adults

OBJECTIVES: To determine the relationship between lower body strength of community-dwelling older adults and the time to negotiate obstructed gait tasks.

DESIGN: A correlational study.

SETTING: The Biomechanics Laboratory, Deakin University, Australia.

PARTICIPANTS: Twenty-nine women and 16 men aged 62 to 88 were recruited using advertisements placed in local newspapers. The participants were independent community dwellers, healthy and functionally mobile.

MEASUREMENTS: Maximal isometric strength of the knee extensors and dynamic strength of the hip extensors, hip flexors, hip adductors, hip abductors, knee extensors, knee flexors, and ankle plantar flexors were assessed. The times to negotiate four obstructed gait tasks at three progressively challenging levels on an obstacle course and to complete the course were recorded. The relationship between strength and the crossing times was explored using linear regression models.

RESULTS: Significant associations between the seven strength measures and the times to negotiate each gait task and to walk the entire course at each level were obtained (r = -0.38 to -0.55; P < .05). In addition, the percentage of the variance explained by strength (R2), consistently increased as a function of the progressively challenging level. This increase was particularly marked for the stepping over task (R2 = 19.3%,25.0%, and 27.2%, for levels 1, 2, and 3, respectively) and the raised surface condition (R2 = 17.1%,21.1%, and 30.8%, for levels 1,2, and 3, respectively) .

CONCLUSION: The findings of the study showed that strength is a critical requirement for obstructed locomotion. That the magnitude of the association increased as a function of the challenging levels suggests that intervention programs aimed at improving strength would potentially be effective in helping community-dwelling older adults negotiate environmental gait challenges.

Does successful treatment of constipation or faecal impaction resolve lower urinary tract symptoms? A structured review of the literature

Consensus guidelines advocate the treatment of constipation and faecal impaction in order to improve symptoms of urinary frequency, urgency and urinary incontinence and to promote bladder emptying in the absence of urinary tract obstruction. This structured review of the literature was undertaken to search for and appraise evidence to support or negate the hypothesis of this relationship. The search strategy was comprehensive and identified six relevant studies. Two of these had been conducted on an adult population and four studies involved children with constipation. These studies were appraised for methodological quality. It was found that sample sizes were small and evidence was inconsistent. Variable methods of reporting meant that data were not able to be pooled for meta-analysis.
Based on the limited and conflicting evidence, it is recommended that further research be undertaken to identify any correlation between bowel and bladder function.

Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function

BACKGROUND: Flavonoids may be partly responsible for some health benefits, including antiinflammatory action and a decreased tendency for the blood to clot. An acute dose of flavanols and oligomeric procyanidins from cocoa powder inhibits platelet activation and function over 6 h in humans. OBJECTIVE: This study sought to evaluate whether 28 d of supplementation with cocoa flavanols and related procyanidin oligomers would modulate human platelet reactivity and primary hemostasis and reduce oxidative markers in vivo. DESIGN: Thirty-two healthy subjects were assigned to consume active (234 mg cocoa flavanols and procyanidins/d) or placebo (< or = 6 mg cocoa flavanols and procyanidins/d) tablets in a blinded parallel-designed study. Platelet function was determined by measuring platelet aggregation, ATP release, and expression of activation-dependent platelet antigens by using flow cytometry. Plasma was analyzed for oxidation markers and antioxidant status. RESULTS: Plasma concentrations of epicatechin and catechin in the active group increased by 81% and 28%, respectively, during the intervention period. The active group had significantly lower P selectin expression and significantly lower ADP-induced aggregation and collagen-induced aggregation than did the placebo group. Plasma ascorbic acid concentrations were significantly higher in the active than in the placebo group (P < 0.05), whereas plasma oxidation markers and antioxidant status did not change in either group. CONCLUSIONS: Cocoa flavanol and procyanidin supplementation for 28 d significantly increased plasma epicatechin and catechin concentrations and significantly decreased platelet function. These data support the results of acute studies that used higher doses of cocoa flavanols and procyanidins.

Determination of lower-bound ductility for AZ31 magnesium alloy by use of the bulge specimens

Despite the high demand for industrial applications of magnesium, the forming technology for wrought magnesium alloys is not fully developed due to the limited ductility and high sensitivity to the processing parameters. The processing window for magnesium alloys could be significantly widened if the lower-bound ductility (LBD) for a range of stresses, temperature, and strain rates was known. LBD is the critical strain at the moment of fracture as a function of stress state and temperature. Measurements of LBD are normally performed by testing in a hyperbaric chamber, which is highly specialized, complex, and rare equipment. In this paper an alternative approach to determine LBD is demonstrated using wrought magnesium alloy AZ31 as an example. A series of compression tests of bulge specimens combined with finite element simulation of the tests were performed. The LBD diagram was then deduced by backward calculation.

Discordance between lung function of Chinese university students of 20-year-old established norms

Objective: We examined the validity of the 20-year-old established Asian norms for pulmonary function in a contemporary cohort of Hong Kong Chinese university students. Design and participants: Pulmonary function testing was conducted in university students (n = 805). Setting: A university campus in Hong Kong. Measurements and results: Parameters recorded included gender, age, height, weight, standard lung function variables (ie, FEV1, FVC, and peak expiratory flow rate [PEFR]), and exhaled carbon monoxide (CO) level. Subjects completed a questionnaire on pulmonary health, smoking history, and their dietary and exercise habits within 3 months of the study. Data were compared with the established norms for lung function for Chinese persons from Hong Kong. On average, subjects were taller than those reported in the original cohort, on whom the established norms are based; however, FEV1, FVC, and PEFR were lower. As predicted, the exhaled CO level was higher in smokers. Those who exercised regularly had a higher FEV1 and FVC, and reported fewer respiratory complaints. Conclusions: Our findings support the idea that lung function norms not only differ across ethnic groups, but that they may be susceptible to change over a single generation within an ethnic group living in the same geographic region. Assuming the equivalence of our testing methods and those on which established norms are based, our findings shed further insight into the dynamic nature of lung function, and have implications regarding the definition of normal pulmonary function and its variance over the short term.

Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention

Context The antioxidant acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who undergo computed tomography scanning. However, its role in coronary angiography is unclear.

Objective To determine whether oral acetylcysteine prevents acute deterioration in renal function in patients with moderate renal insufficiency who undergo elective coronary angiography.

Design and Setting Prospective, randomized, double-blind, placebo-controlled trial conducted from May 2000 to December 2001 at the Grantham Hospital at the University of Hong Kong.

Participants Two hundred Chinese patients aged mean (SD) 68 (6.5) years with stable moderate renal insufficiency (creatinine clearance <60 mL/min [1.00 mL/s]) who were undergoing elective coronary angiography with or without intervention.

Intervention Participants were randomly assigned to receive oral acetylcysteine(600 mg twice per day; n = 102) or matching placebo tablets (n = 98) on the day before and the day of angiography. All patients received low-osmolality contrast agent.

Main Outcome Measures Occurrence of more than a 25% increase in serum creatinine level within 48 hours after contrast administration; change in creatinine clearance and serum creatinine level.

Results Twelve control patients (12%) and 4 acetylcysteine patients (4%) developed a more than 25% increase in serum creatinine level within 48 hours after contrast administration (relative risk, 0.32; 95% confidence interval [CI], 0.10-0.96; P = .03). Serum creatinine was lower in the acetylcysteine group (1.22 mg/dL [107.8 µmol/L]; 95% CI, 1.11-1.33 mg/dL vs 1.38 mg/dL [122.9 µmol/L]; 95% CI, 1.27-1.49 mg/dL; P = .006) during the first 48 hours after angiography. Acetylcysteine treatment significantly increased creatinine clearance from 44.8 mL/min (0.75 mL/s) (95% CI, 42.7-47.6 mL/min) to 58.9 mL/min (0.98 mL/s) (95% CI, 55.6-62.3 mL/min) 2 days after the contrast administration (P<.001).The increase was not significant in the control group (from 42.1 to 44.1 mL/min [0.70 to 0.74 mL/s]; P = .15). The benefit of acetylcysteine was consistent among various patient subgroups and persistent for at least 7 days. There were no major treatment-related adverse events.

Conclusion Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures, with minimal adverse effects and at a low cost.

Tensile behaviour of wool fabric as a function of fabric pH

Wool fabric extensibility under a 5 N/cm load was observed to be greatest at the wool isoelectric point of pH 4.8 and lower at both pH 2.1 and pH 7.2. The impact of pH on fabric extensibility is similar to the variation in fabric hygral expansion previously observed. Fabric stress-strain curves at different pHs show that for a given fabric extension level, the work required to stretch a fabric was less at pH 2.1 than at pH 4.8. These results confirm the fact that the strength of wool fabric is at a maximum when the pH of the fibres is close to the isoelectric point.

Risk of sexual recidivism as a function of age and actuarial risk

The study of risk for sexual recidivism has undergone substantial development in recent years. The foundation for advances in this area has been the use of actuarial measures to identify subgroups of offenders with different observed rates of sexual re-offending over time. An unresolved issue within this research area has been the moderating function of age in the assessment of risk. The current study examined sexual re-offending as a function of age and actuarial risk in a large sample of sexual offenders released from prison between 1990 and 2004. There was an overall decrease in the rate of sexual re-offending over the age of 50. However, a small group of offenders from the higher actuarial risk categories of the older age groups continued to re-offend at higher rates than their lower-risk peers.

The effects of treating male hypogonadism on couples' sexual desire and function

Introduction: Hypogonadism is a common endocrine condition characterized by low levels of testosterone (T) and marked by numerous symptoms, one of which is low sexual desire. Studies comparing T delivery systems have suggested that hypogonadal men’s partners may be at risk from exposure to T gels. Little other mention is found of the impact of hypogonadism and its treatment on a man’s partner and the couple’s sexual function.

Aim: To assess sexual desire and sexual function in hypogonadal men and their woman partners before and after treatment with T replacement therapy.

Methods: Twenty-one hypogonadal men and 18 partners were recruited from a   tertiary endocrine clinic, and were compared with a control group of 20 eugonadal age-matched men and their partners. All men had baseline blood tests to confirm their status as hypogonadal or eugonadal, and hypogonadal men repeated tests at 3-month intervals. All participants completed the Sexual Desire Inventory (SDI) and sexual function questionnaires at baseline and at 3-month intervals until the hypogonadal men attained normal T levels.

Main Outcome Measures: Pre- and post-treatment SDI and sexual function questionnaires were compared once T normalization was achieved. Between- and within-group comparisons were carried out.

Results: Pretreatment hypogonadal men recorded lower levels of sexual desire and function than controls, but significantly improved once hypogonadism was corrected. Eugonadal controls recorded no significant changes in either sexual desire or function during the study. Partners of the hypogonadal men reported no changes on the SDI, but significant improvements in sexual function as their partners recovered.

Conclusion: SDI and sexual function measures reflect sexual changes that  accompany rising serum T levels during correction of male hypogonadism. Women partners reported more satisfaction, less pain, and improved sexual function following the men’s treatment. Treatments affecting one partner potentially have important effects on the other.

Severely compromised quality of life in women and those of lower socioeconomic status waiting for joint replacement surgery

Objective
To determine health-related quality of life (HRQOL), psychological distress, physical function, and self efficacy in persons waiting for lower-limb joint replacement surgery.

Methods
A total of 214 patients on a waiting list for unilateral primary total knee or hip replacement at a large Australian public teaching hospital completed questionnaires after entry to the list. HRQOL and psychological distress were compared with available population norms.

Results
Average HRQOL was extremely poor (mean ± SD 0.39 ± 0.24) and much lower (>2 SD) than the population norm. Near death-equivalent HRQOL or worse than death-equivalent HRQOL were reported by 15% of participants. High or very high psychological distress was up to 5 times more prevalent in the waiting list sample (relative risk 5.4 for participants ages 75 years and older; 95% confidence interval 3.3, 9.0). Women had significantly lower HRQOL, self efficacy, and physical function scores than men. After adjusting for age and sex, significant socioeconomic disparities were also found. Participants who received the lowest income had the poorest HRQOL; those with the least education or the lowest income had the highest psychological distress. Low self efficacy was moderately associated with poor HRQOL (r = 0.49, P < 0.001) and more strongly associated with high psychological distress (r = -0.55, P < 0.001).

Conclusion
Patients waiting for joint replacement have very poor HRQOL and high psychological distress, especially women and those from lower socioeconomic backgrounds. Lengthy waiting lists mean patients can experience extended and potentially avoidable morbidity. Interventions to address psychological distress and self efficacy could reduce this burden and should target women and lower socioeconomic groups.