Normal Ribosomal Biogenesis but Shortened Protein Synthetic Response to Acute Eccentric Resistance Exercise in Old Skeletal Muscle.

Anabolic resistance to feeding in aged muscle is well-characterized; however, whether old skeletal muscle is intrinsically resistant to acute mechanical loading is less clear. The aim of this study was to determine the impact of aging on muscle protein synthesis (MPS), ribosome biogenesis, and protein breakdown in skeletal muscle following a single bout of resistance exercise. Adult male F344/BN rats aged 10 (Adult) and 30 (Old) months underwent unilateral maximal eccentric contractions of the hindlimb. Precursor rRNA increased early post-exercise (6-18 h), preceding elevations in ribosomal mass at 48 h in Adult and Old; there were no age-related differences in these responses. MPS increased early post-exercise in both Adult and Old; however, at 48 h of recovery, MPS returned to baseline in Old but not Adult. This abbreviated protein synthesis response in Old was associated with decreased levels of IRS1 protein and increased BiP, CHOP and eIF2α levels. Other than these responses, anabolic signaling was similar in Adult and Old muscle in the acute recovery phase. Basal proteasome activity was lower in Old, and resistance exercise did not increase the activity of either the ATP-dependent or independent proteasome, or autophagy (Cathepsin L activity) in either Adult or Old muscle. We conclude that MPS and ribosome biogenesis in response to maximal resistance exercise in old skeletal muscle are initially intact; however, the MPS response is abbreviated in Old, which may be the result of ER stress and/or blunted exercise-induced potentiation of the MPS response to feeding

Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis.

Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength

Prognostic utility of sestamibi lung uptake does not require adjustment for stress-related variables: A retrospective cohort study

BACKGROUND: Increased (99m)Tc-sestamibi stress lung-to-heart ratio (sLHR) has been shown to predict cardiac outcomes similar to pulmonary uptake of thallium. Peak heart rate and use of pharmacologic stress affect the interpretation of lung thallium uptake. The current study was performed to determine whether (99m)Tc-sestamibi sLHR measurements are affected by stress-related variables, and whether this in turn affects prognostic utility. METHODS: sLHR was determined in 718 patients undergoing (99m)Tc-sestamibi SPECT stress imaging. sLHR was assessed in relation to demographics, hemodynamic variables and outcomes (mean follow up 5.6 ± 1.1 years). RESULTS: Mean sLHR was slightly greater in males than in females (P < 0.01) and also showed a weak negative correlation with age (P < 0.01) and systolic blood pressure (P < 0.01), but was unrelated to stress method or heart rate at the time of injection. In patients undergoing treadmill exercise, sLHR was also positively correlated with peak workload (P < 0.05) but inversely with double product (P < 0.05). The combined explanatory effect of sex, age and hemodynamic variables on sLHR was less than 10%. The risk of acute myocardial infarction (AMI) or death increased by a factor of 1.7–1.8 for each SD increase in unadjusted sLHR, and was unaffected by adjustment for sex, age and hemodynamic variables (hazard ratios 1.6–1.7). The area under the ROC curve for the unadjusted sLHR was 0.65 (95% CI 0.59–0.71, P < 0.0001) and was unchanged for the adjusted sLHR (0.65, 95% CI 0.61–0.72, P < 0.0001). CONCLUSION: Stress-related variables have only a weak effect on measured sLHR. Unadjusted and adjusted sLHR provide equivalent prognostic information for prediction of AMI or death

Osteoporosis-related fracture case definitions for population-based administrative data

<p>Abstract</p> <p>Background</p> <p>Population-based administrative data have been used to study osteoporosis-related fracture risk factors and outcomes, but there has been limited research about the validity of these data for ascertaining fracture cases. The objectives of this study were to: (a) compare fracture incidence estimates from administrative data with estimates from population-based clinically-validated data, and (b) test for differences in incidence estimates from multiple administrative data case definitions.</p> <p>Methods</p> <p>Thirty-five case definitions for incident fractures of the hip, wrist, humerus, and clinical vertebrae were constructed using diagnosis codes in hospital data and diagnosis and service codes in physician billing data from Manitoba, Canada. Clinically-validated fractures were identified from the Canadian Multicentre Osteoporosis Study (CaMos). Generalized linear models were used to test for differences in incidence estimates.</p> <p>Results</p> <p>For hip fracture, sex-specific differences were observed in the magnitude of under- and over-ascertainment of administrative data case definitions when compared with CaMos data. The length of the fracture-free period to ascertain incident cases had a variable effect on over-ascertainment across fracture sites, as did the use of imaging, fixation, or repair service codes. Case definitions based on hospital data resulted in under-ascertainment of incident clinical vertebral fractures. There were no significant differences in trend estimates for wrist, humerus, and clinical vertebral case definitions.</p> <p>Conclusions</p> <p>The validity of administrative data for estimating fracture incidence depends on the site and features of the case definition.</p

Educational difference in the prevalence of osteoporosis in postmenopausal women: a study in northern Iran

<p>Abstract</p> <p>Background</p> <p>Osteoporosis is the most common metabolic bone disease in the world and it is rapidly increasing in Iran. In this study the relationship between educational levels and osteoporosis was investigated among Iranian postmenopausal women.</p> <p>Method and subjects</p> <p>Seven hundred and six women aged 50-75 years old were randomly recruited from urban (<it>n </it>= 440) and rural (<it>n </it>= 266) areas in Guilan. Osteoporosis was diagnosed by quantitative ultrasound technique and dual X-ray absorptiometry. Serum 25(OH) D3, body weight and height were measured in all subjects. Other data including age, educational level, menopause age, medications and history of illness were also collected.</p> <p>Results</p> <p>We found that the prevalence of osteoporosis was significantly greater among women with low educational level than women with high educational status (18.0% vs 3.8% <it>P </it>< 0.0001). However, women with low educational level had higher mean serum level of vitamin D than women with high educational level. Osteoporosis was significantly more prevalent among women living in rural areas than women living in urban areas (19.1% v.s 13.3%, <it>P </it>< 0.0001).</p> <p>Conclusion</p> <p>This study showed that educational level is associated with bone health in this population of postmenopausal women with significantly higher osteoporosis found in lower social groups. Therefore, we suggest that women with low social level should be carefully evaluated for signs of osteoporosis during routine physical examinations.</p

ICD-10 coding algorithms for defining comorbidities of acute myocardial infarction

BACKGROUND: With the introduction of ICD-10 throughout Canada, it is important to ensure that Acute Myocardial Infarction (AMI) comorbidities employed in risk adjustment methods remain valid and robust. Therefore, we developed ICD-10 coding algorithms for nine AMI comorbidities, examined the validity of the ICD-10 and ICD-9 coding algorithms in detection of these comorbidities, and assessed their performance in predicting mortality. The nine comorbidities that we examined were shock, diabetes with complications, congestive heart failure, cancer, cerebrovascular disease, pulmonary edema, acute renal failure, chronic renal failure, and cardiac dysrhythmias. METHODS: Coders generated a comprehensive list of ICD-10 codes corresponding to each AMI comorbidity. Physicians independently reviewed and determined the clinical relevance of each item on the list. To ensure that the newly developed ICD-10 coding algorithms were valid in recording comorbidities, medical charts were reviewed. After assessing ICD-10 algorithms' validity, both ICD-10 and ICD-9 algorithms were applied to a Canadian provincial hospital discharge database to predict in-hospital, 30-day, and 1-year mortality. RESULTS: Compared to chart review data as a 'criterion standard', ICD-9 and ICD-10 data had similar sensitivities (ranging from 7.1 – 100%), and specificities (above 93.6%) for each of the nine AMI comorbidities studied. The frequencies for the comorbidities were similar between ICD-9 and ICD-10 coding algorithms for 49,861 AMI patients in a Canadian province during 1994 – 2004. The C-statistics for predicting 30-day and 1 year mortality were the same for ICD-9 (0.82) and for ICD-10 data (0.81). CONCLUSION: The ICD-10 coding algorithms developed in this study to define AMI comorbidities performed similarly as past ICD-9 coding algorithms in detecting conditions and risk-adjustment in our sample. However, the ICD-10 coding algorithms should be further validated in external databases

FRAX (R): Prediction of Major Osteoporotic Fractures in Women from the General Population: The OPUS Study

Purposes: The aim of this study was to analyse how well FRAXH predicts the risk of major osteoporotic and vertebral fractures over 6 years in postmenopausal women from general population. Patients and methods: The OPUS study was conducted in European women aged above 55 years, recruited in 5 centers from random population samples and followed over 6 years. The population for this study consisted of 1748 women (mean age 74.2 years) with information on incident fractures. 742 (43.1%) had a prevalent fracture; 769 (44%) and 155 (8.9%) of them received an antiosteoporotic treatment before and during the study respectively. We compared FRAXH performance with and without bone mineral density (BMD) using receiver operator characteristic (ROC) c-statistical analysis with ORs and areas under receiver operating characteristics curves (AUCs) and net reclassification improvement (NRI). Results: 85 (4.9%) patients had incident major fractures over 6 years. FRAXH with and without BMD predicted these fractures with an AUC of 0.66 and 0.62 respectively. The AUC were 0.60, 0.66, 0.69 for history of low trauma fracture alone, age and femoral neck (FN) BMD and combination of the 3 clinical risk factors, respectively. FRAXH with and without BMD predicted incident radiographic vertebral fracture (n = 65) with an AUC of 0.67 and 0.65 respectively. NRI analysis showed a significant improvement in risk assignment when BMD is added to FRAXH. Conclusions: This study shows that FRAXH with BMD and to a lesser extent also without FN BMD predict major osteoporotic and vertebral fractures in the general population

Two Earth-sized planets orbiting Kepler-20

Since the discovery of the first extrasolar giant planets around Sun-like stars, evolving observational capabilities have brought us closer to the detection of true Earth analogues. The size of an exoplanet can be determined when it periodically passes in front of (transits) its parent star, causing a decrease in starlight proportional to its radius. The smallest exoplanet hitherto discovered has a radius 1.42 times that of the Earth's radius (R Earth), and hence has 2.9 times its volume. Here we report the discovery of two planets, one Earth-sized (1.03R Earth) and the other smaller than the Earth (0.87R Earth), orbiting the star Kepler-20, which is already known to host three other, larger, transiting planets. The gravitational pull of the new planets on the parent star is too small to measure with current instrumentation. We apply a statistical method to show that the likelihood of the planetary interpretation of the transit signals is more than three orders of magnitude larger than that of the alternative hypothesis that the signals result from an eclipsing binary star. Theoretical considerations imply that these planets are rocky, with a composition of iron and silicate. The outer planet could have developed a thick water vapour atmosphere.Comment: Letter to Nature; Received 8 November; accepted 13 December 2011; Published online 20 December 201