Stretch training induces unequal adaptation in muscle fascicles and thickness in medial and lateral gastrocnemii.

This study compared adaptations in fascicle lengths, pennation angles, and muscle thickness of the lateral and medial gastrocnemii in response to 6 weeks of stretch training. The nondominant plantar flexors of 11 males were stretched five times per week for 6 weeks and compared with the contralateral leg and a nonstretched control group of 10 males. During stretch training, instantaneous electromyography was utilized to ensure passive muscle stretch. At baseline, week three, week six and 1 week after the conclusion of stretch training, ultrasound was used to measure fascicle lengths, pennation angles, muscle thickness of the lateral gastrocnemius and medial gastrocnemius, and Achilles tendon thickness and length. Plantar flexion torque was measured, and voluntary activation was assessed. Muscle thickness increased 5.6% after 6 weeks of stretch training (P=.009). The fascicles in the lateral gastrocnemius lengthened to a greater extent than the medial. Overall, fascicles lengthened 25% (P<.001) in the muscle tendon junction and 5.1% (P<.001) in the muscle belly. Pennation angles were unchanged in the medial gastrocnemius but decreased in the lateral gastrocnemius 7.1% (P=.02). There was no change in maximal voluntary contraction, voluntary activation, tendon length, or thickness. This study demonstrates that stretch training is a viable modality to alter muscle architecture of the human gastrocnemius through lengthening of muscle fascicles, decreasing pennation angles, and increasing muscle thickness, albeit adaptations are unequal between the lateral and medial heads.

How is income generated by outpatient parenteral antibiotic treatment (OPAT) in the UK? Analysis of payment tariffs for cellulitis.

OBJECTIVES: We determined the available mechanisms to generate income from outpatient parenteral antimicrobial therapy (OPAT) in the UK and calculated the revenue generated from treatment of an episode of cellulitis. METHODS: Revenue was calculated for patients receiving treatment for cellulitis as an inpatient and for patients receiving OPAT by a series of different payment pathways. Selected established OPAT services in Northern Ireland, Scotland and Wales, where Payment-by-Results (PbR) does not operate, were contacted to determine individual national funding arrangements. RESULTS: In England, a traditional inpatient episode for uncomplicated cellulitis requiring 7 days of treatment generated £1361 of revenue, while OPAT generated revenue ranging from £773 to £2084 for the same length of treatment depending on the payment pathway used. Treatment using OPAT to avoid admission entirely generated £2084, inpatient admission followed by transfer to a virtual OPAT ward at day 2 generated £1361 and inpatient admission followed by discharge from hospital to OPAT at day 2 generated £773. In Northern Ireland, Scotland and Wales block contracts were used and no income was calculable for an individual episode of cellulitis. CONCLUSIONS: No single funding mechanism supports OPAT across the UK. In England, revenue generated by OPAT providers from treatment of cellulitis varied with the OPAT payment pathway used, but equalled or exceeded the income generated from equivalent inpatient care. Cost savings for OPAT and reuse of released inpatient beds will increase revenue further. A single OPAT tariff is proposed.

Performance of formulas for estimating glomerular filtration rate in Indigenous Australians with and without Type 2 diabetes: the eGFR Study.

AIMS: It has been proposed that the Chronic Kidney Disease Epidemiology Collaboration formula estimates glomerular filtration rate more accurately than the Modification of Diet in Renal Disease formula. With the very high incidence of diabetes and end-stage kidney disease in Indigenous Australians, accurate estimation of glomerular filtration rate is vital in early detection of kidney disease. We aimed to assess the performance of the Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease and Cockcroft-Gault formulas in Indigenous Australians with and without diabetes. METHODS: Indigenous Australians with (n = 224) or without (n = 340) Type 2 diabetes had a reference glomerular filtration rate measure using plasma disappearance of iohexol (measured glomerular filtration rate) over 4 h. Serum creatinine was measured by an enzymatic method. Performance was assessed by bias (measured glomerular filtration rate - estimated glomerular filtration rate) and accuracy (percentage of estimated glomerular filtration rate within 30% of measured glomerular filtration rate). RESULTS: The median measured glomerular filtration rate (interquartile range) in participants with or without diabetes was 97 (68-119) and 108 (90-122) ml min(-1)  1.73 m(-2) , respectively. The Chronic Kidney Disease Epidemiology Collaboration formula had smaller bias and greater accuracy than the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall, for participants both with and without diabetes. However, for estimated glomerular filtration rate > 90 ml min(-1)  1.73 m(-2) , the Chronic Kidney Disease Epidemiology Collaboration formula had greater bias in participants with diabetes, underestimating measured glomerular filtration rate by 7.4 vs. 1.0 ml min(-1)  1.73 m(-2) in those without diabetes. The Chronic Kidney Disease Epidemiology Collaboration formula was less accurate across the whole range of estimated glomerular filtration rates in participants with vs. those without diabetes (87.1% vs. 93.3%). CONCLUSIONS: The Chronic Kidney Disease Epidemiology Collaboration formula outperforms the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall in Indigenous Australians with and without diabetes. However, the Chronic Kidney Disease Epidemiology Collaboration formula has greater bias in people with diabetes compared with those without diabetes, especially in those with normal renal function.

Audit of acute Charcot's disease in the UK: the CDUK study.

AIMS/HYPOTHESIS: We studied factors associated with the development and resolution of acute Charcot foot using a web-based observational study. METHODS: Clinicians managing cases of acute Charcot foot in the UK and Ireland between June 2005 and February 2007 were invited to register anonymised details on a secure website. RESULTS: A total of 288 cases (age 57.0 ± 11.3 years [mean ± SD]; 71.2% male) were registered from 76 centres. Of these, 36% of patients recalled an episode of relevant trauma in the preceding 6 months, while 12% had had surgery to the affected foot. In 101 (35%) cases, ulceration was present at registration and 20% of these had osteomyelitis. Non-removable off-loading devices were used at presentation in 35.4% of cases, with removable off-loading used in 50%. Data on resolution were available for 219 patients. The median time to resolution was 9 months in patients whose initial management included the use of non-removable off-loading, compared with 12 months in the remainder (p = 0.001). Bisphosphonates were administered intravenously in 25.4% and orally in 19.4% of cases. The median time to resolution in patients who received bisphosphonates was 12 months and was longer than in those who did not (10 months, p = 0.005). CONCLUSIONS/INTERPRETATION: The median time to resolution was longer than in earlier series. Although limited by being observational and non-randomised, these data suggest that the use of non-removable off-loading at presentation may shorten the time to resolution. They provide no evidence to indicate that the use of bisphosphonates is beneficial.

Hyperglycaemia in hospital inpatients: still a sticky situation.

BACKGROUND: Diabetes diagnosis is delayed 4-7 years and 50% are undiagnosed. Forty percent of hospitalized patients with any blood glucose level (BGL) > or = 10 mmol/L have diabetes 3 months post-discharge, yet less than 5% are detected in hospital. We review identification of, and responses to, hyperglycaemia in inpatients at a teaching hospital. METHODS: The world's largest retrospective review of medical records for inpatients with venous BGL > or = 11.1 mmol/L without known diabetes over 12 months (2005-2006). The primary outcome was recognition of hyperglycaemia; secondary outcomes were treatment and documentation of follow up. Logistic regression was performed with variables including BGL, admitting team, length of stay and endocrine team review. RESULTS: Of 10 973 people screened, 162 were eligible. The median age was 58 years and BGL 13.3 mmol/L, with increased mortality and length of stay. Hyperglycaemia was noted as definitely in 26%, maybe in 24% and definitely not in 50%. Forty percent of patients were treated in hospital and 19% on discharge. Follow up was documented for 24%. A higher BGL and review by the endocrine team were strongly associated with clinical recognition on uni- and multivariate analyses. However, where an endocrine review was sought for non-hyperglycaemia reasons, similar rates of non-recognition occurred. CONCLUSION: Despite evidence for improved inpatient outcomes when treated, and high short-term progression to frank diabetes, inpatient hyperglycaemia remains frequently missed. In-hospital recognition is cheap, and vital for the implementation of activities to improve outcomes and prevent progression and complications. Changes to systems for checking pathology results, medical officer education and inpatient screening guidelines are indicated.

Age and sex-related decline of muscle strength across the adult lifespan: a scoping review of aggregated data.

Muscle strength is sex-related and declines with advancing age; yet, a comprehensive comparative evaluation of age-related strength loss in human females and males has not been undertaken. To do so, segmented piecewise regression analysis was performed on aggregated data from studies published from 1990 to 2018 and are available in CINAHL, EMBASE, MEDLINE, and PsycINFO databases. The search identified 5613 articles that were reviewed for physical assessment results stratified by sex and age. Maximal isometric and isokinetic 60°·s-1 knee extension (KE) and knee flexion (KF) contractions from 57 studies and 15 283 subjects (N = 7918 females) had sufficient data reported on females and males for meaningful statistical evaluation to be undertaken. The analysis revealed that isometric KE and KF strength undergo similar rapid declines in both sexes late in the sixth decade of life. Yet, there is an abrupt age-related decline in KE 60°·s-1 peak torque earlier in females (aged 41.8 years) than males (aged 66.7 years). In the assessment of KF peak torque, an age-related acceleration in strength loss was only identified in males (aged 49.3 years). The results suggest that age-related isometric strength loss is similar between sexes while the characteristics of KE and KF peak torque decline are sex-related, which likely explains the differential rate of age-related functional decline. Novelty Inclusion of muscle strength and torque of KE and KF data from >15 000 subjects. Isometric KE and KF strength loss are similar between sexes. Isokinetic 60°·s-1 KE torque decline accelerates 25 years earlier in females and female age-related KF peak torque decline does not accelerate with age.

Temporal Trends in Surgical Resection Rates and Biologic Prescribing in Crohn's Disease: A Population-based Cohort Study.

BACKGROUND: The use of biologic therapy for Crohn's disease [CD] continues to evolve, however, the effect of this on the requirement for surgery remains unclear. We assessed changes in biologic prescription and surgery over time in a population-based cohort. METHODS: We performed a retrospective cohort study of all 1753 patients diagnosed with CD in Lothian, Scotland, between January 1, 2000 and December 31, 2017, reviewing the electronic health record of each patient to identify all CD-related surgery and biologic prescription. Cumulative probability and hazard ratios for surgery and biologic prescription from diagnosis were calculated and compared using the log-rank test and Cox regression analysis stratified by year of diagnosis into cohorts. RESULTS: The 5-year cumulative risk of surgery was 20.4% in cohort 1 [2000-2004],18.3% in cohort 2 [2005-2008], 14.7% in cohort 3 [2009-2013], and 13.0% in cohort 4 [2014-2017] p <0.001. The 5-year cumulative risk of biologic prescription was 5.7% in cohort 1, 12.2% in cohort 2, 22.0% in cohort 3, and 44.9% in cohort 4 p <0.001. CONCLUSIONS: The increased and earlier use of biologic therapy in CD patients corresponded with a decreasing requirement for surgery over time within our cohort. This could mean that adopting a top-down or accelerated step-up treatment strategy may be effective at reducing the requirement for surgery in newly diagnosed CD.

Towards precision dosing of vancomycin in critically ill patients: an evaluation of the predictive performance of pharmacometric models in ICU patients.

OBJECTIVES: Vancomycin dose recommendations depend on population pharmacokinetic models. These models have not been adequately assessed in critically ill patients, who exhibit large pharmacokinetic variability. This study evaluated model predictive performance in intensive care unit (ICU) patients and identified factors influencing model performance. METHODS: Retrospective data from ICU adult patients administered vancomycin were used to evaluate model performance to predict serum concentrations a priori (no observed concentrations included) or with Bayesian forecasting (using concentration data). Predictive performance was determined using relative bias (rBias, bias) and relative root mean squared error (rRMSE, precision). Models were considered clinically acceptable if rBias was between ±20% and 95% confidence intervals included zero. Models were compared with rRMSE; no threshold was used. The influence of clinical factors on model performance was assessed with multiple linear regression. RESULTS: Data from 82 patients were used to evaluate 12 vancomycin models. The Goti model was the only clinically acceptable model with both a priori (rBias 3.4%) and Bayesian forecasting (rBias 1.5%) approaches. Bayesian forecasting was superior to a priori prediction, improving with the use of more recent concentrations. Four models were clinically acceptable with Bayesian forecasting. Renal replacement therapy status (p < 0.001) and sex (p = 0.007) significantly influenced the performance of the Goti model. CONCLUSIONS: The Goti, Llopis and Roberts models are clinically appropriate to inform vancomycin dosing in critically ill patients. Implementing the Goti model in dose prediction software could streamline dosing across both ICU and non-ICU patients, considering it is also the most accurate model in non-ICU patients.

Xenon Hexafluoride: Structure of a Cubic Phase at -80{degrees}C.

The crystal structure of a cubic phase of composition XeF(6) has been determined at -80 degrees C. There are no simple molecules in the complex structure which involves 1008 atoms distributed over 1600 positions per unit cell. Ions of XeF(5)+ and F- are associated in tetrameric and hexameric rings of point group symmetries 4 and 32, respectively. The structure contains right-and left-handed conformations of both tetramers and hexamers. The handedness of the tetramers is dis-ordered but the orientation is ordered. The handedness of the hexamers is ordered but the orientation is disordered.

Xenon hexafluoride: structural crystallography of tetrameric phases.

Three crystalline phases of xenon hexafluoride are based on tetrameric association of XeF(5)(+) and F(-) ions into eight-membered rings. Phase I (monoclinic, 8 XeF(6) units per cell) transforms at approximately 10 degrees C to phase II (orthorhombic, 16 XeF(6) units per cell), which in turn transforms at approximately -25 degrees C to phase 111 (monoclinic, 64 XeF(6) units per doubly primitive cell). The transformation from phase I to phase II requires gross reorientation of half of the tetramers in the structure. The transformation from phase II to phase III involves only an ordering of right-handed and left-handed configurations.

Introduction of a normal human chromosome 11 into a Wilms' tumor cell line controls its tumorigenic expression.

The development of Wilms' tumor, a pediatric nephroblastoma, has been associated with a deletion in the p13 region of chromosome 11. The structure and function or functions of this deleted genetic material are unknown. The role of this deletion in the process of malignant transformation was investigated by introducing a normal human chromosome 11 into a Wilms' tumor cell line by means of the microcell transfer technique. These variant cells, derived by microcell hybridization, expressed similar transformed traits in culture as the parental cell line. Furthermore, expression of several proto-oncogenes by the parental cells was unaffected by the introduction of this chromosome. However, the ability of these cells to form tumors in nude mice was completely suppressed. Transfer of other chromosomes, namely X and 13, had no effect on the tumorigenicity of the Wilms' tumor cells. These studies provide support for the existence of genetic information on chromosome 11 which can control the malignant expression of Wilms' tumor cells.

Faecal Calprotectin and Magnetic Resonance Enterography in Ileal Crohn's Disease: Correlations Between Disease Activity and Long-Term Follow-Up.

BACKGROUND AND AIMS: Magnetic resonance enterography [MRE] is the gold standard for assessing ileal inflammation in Crohn's disease [CD]. The aim of the present study was to correlate faecal calprotectin [FC] to MRE via a simple score in an exclusive ileal cohort with long-term follow-up for association with time to surgery or biologic therapy. METHODS: In total, 150 MRE studies with matched FC [±30 days] were identified from the Edinburgh FC Register [2008-12; n = 18138]. Scans were re-read blinded to clinical data, independently, by two expert gastrointestinal radiologists, to generate a simple MRE score [range 0-10] from assessment of the worst intestinal segment plus total disease extent. RESULTS: In total, 119 MRE scans were evaluated from 104 patients with ileal CD [L1 or L3 with panproctocolectomy]. Receiver operating characteristic analysis showed an area under the curve of 0.77 [0.67-0.87, p < 0.0001] for FC and MRE score >1, with an optimal cut-off of 145 µg/g for severe inflammation on MRE with 69.3% [57.6-79.5] sensitivity and 71.4% [53.7-85.4] specificity. Long-term follow-up over a median [interquartile range] of 2086 days [1786-2353] revealed FC ≥ 145 µg/g was associated with reduced biologic-free survival until 3 years following MRE, whereas MRE score [severe vs absent] was associated with reduced surgery- and biologic-free survival throughout follow-up. Backwards stepwise logistic regression revealed that length of ileal disease (odds ratio [OR] 3.8, 1.1-13.2, p = 0.034) and increased bowel wall thickness at MRE [OR 4.2, 1.6-10.7, p < 0.0001] or female sex [OR 5.2, 1.5-18.7, p = 0.011] increased the risk of biologic use or surgery, respectively. CONCLUSIONS: FC correlates well with MRE assessment of ileal CD with MRE parameters associated with long-term biologic- and surgery-free remission.

Real-world Effectiveness and Safety of Vedolizumab for the Treatment of Inflammatory Bowel Disease: The Scottish Vedolizumab Cohort.

BACKGROUND & AIMS: Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn's disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. METHODS: This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn's disease with objective evidence of active inflammation at baseline (Harvey-Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. RESULTS: Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn's disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26-52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn's disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. CONCLUSIONS: Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn's disease.

Chromatic techniques for in vivo monitoring jaundice in neonate tissues.

OBJECTIVE: A chromatic method is described for providing a preliminary indication of unacceptable bilirubin levels in a newly born baby in order to avoid the development of serious mental deficiencies. The aim was to investigate the reliability of a new chromatic approach using a novel template unit for a preliminary, non-invasive monitoring of the skin tissue of newly born babies with jaundice and its capability for use with different mobile phone cameras. APPROACH: A description of the monitoring system is given along with an explanation of the monitoring technique used. Preliminary tests have been performed on 48 different neonates each being addressed by one of six different mobile phone cameras, which were randomly available to the operating clinicians. MAIN RESULTS: The test results have a correlation (R 2) of 0.81, a sensitivity (Sn) of 0.97, a specificity (Sp) of 0.82, a positive predictive value (PPV) of 0.95 and a negative predictive value (NPV) of 0.9. SIGNIFICANCE: The significance of the results obtained is that they show the approach to have a high level of fail-safe reliability in indicating the bilirubin levels when compared with blood test results. The results also show that the approach can be used with a few different mobile phone cameras and that because of its non-invasive nature and its cost effectiveness, has the potential for remote use from a medical hospital to provide an immediate preliminary diagnosis.

Physical activity levels of community-dwelling older adults are influenced by winter weather variables.

Winter weather conditions may negatively influence participation of older adults in daily physical activity (PA). OBJECTIVE: Assess the influence of winter meteorological variables, day-time peak ambient temperature, windchill, humidity, and snow accumulation on the ground to accelerometer measured PA values in older adults. METHODS: 50 community-dwelling older adults (77.4±4.7yrs; range 71-89; 12 females) living in Southwestern Ontario (Latitude 42.9°N Longitude 81.2° W) Canada, wore a waist-borne accelerometer during active waking hours (12h) for 7 consecutive days between February and April 2007. Hourly temperature, windchill, humidity, and snowfall accumulation were obtained from meteorological records and time locked to hourly accelerometer PA values. CONCLUSIONS: Regression analysis revealed significant relationships between time of day, ambient daytime high temperature and a humidity for participation in PA. Windchill temperature added no additional influence over PA acclamation already influenced by ambient day-time temperature and the observed variability in PA patterns relative to snow accumulation over the study period was too great to warrant its inclusion in the model. Most PA was completed in the morning hours and increased as the winter month's transitioned to spring (February through April). PRACTICE: An equation was developed to adjust for winter weather conditions using temperature, humidity and time of day. IMPLICATIONS: Accurate PA assessment during the winter months must account for the ambient daytime high temperatures, humidity, and time of day. These older adults were more physically active during the morning hours and became more active as the winter season transitioned to spring.

Bilirubin concentration is positively associated with haemoglobin concentration and inversely associated with albumin to creatinine ratio among Indigenous Australians: eGFR Study.

Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD). HYPOTHESIS: serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians. METHOD: A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Measures included urine albumin: creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), haemoglobin (Hb) and glycated haemoglobin (HbA1c). Diabetes was defined by medical history, medications or HbA1c≥6.5% or ≥48mmol/mol. Anaemia was defined as Hb<130g/L or <120g/L in males and females respectively. A multivariate regression analysis examining factors independently associated with log-bilirubin was performed. RESULTS: Participants mean (SD) age was 45.1 (14.5) years, and included 62.5% females, 71.7% Aboriginal, 41.1% with diabetes, 16.7% with anaemia, 41% with ACR>3mg/mmol and 18.2% with eGFR<60mL/min/1.73m2. Median bilirubin concentration was lower in females than males (6 v 8µmol/L, p<0.001) and in Aboriginal than TSI participants (6 v 9.5µmol/L, p<0.001). Six factors explained 35% of the variance of log-bilirubin; Hb and cholesterol (both positively related) and ACR, triglycerides, Aboriginal ethnicity and female gender (all inversely related). CONCLUSION: Serum bilirubin concentrations were positively associated with Hb and total cholesterol, and inversely associated with ACR. Further research to determine reasons explaining lower bilirubin concentrations among Aboriginal compared with TSI participants are needed.

Tumorigenicity and oncogene expression in pediatric cancers.

Cytogenetic and epidemiological studies of pediatric cancers have implicated a loss of genetic information in the development of these tumors. In contrast, other studies have shown that activation of endogenous oncogenes is a common event in these cancer cells. The technique of somatic cell hybridization provides a model for investigating the interaction between loss of genetic elements and oncogene activation in pediatric cancers. A variety of human-human cell hybrids were formed between a tumorigenic adult carcinoma and representative tumorigenic pediatric cell lines. All hybrid cells were completely suppressed for tumor-forming ability when assayed in nu/nu (nude) mice. When the expression of the N-myc, c-myc, and sis oncogenes and tumorigenicity were examined in the same hybrid cells, no correlation was found, suggesting that the expression of these oncogenes in these hybrid cells did not appear to be controlled by putative "tumor suppressor" genes. Thus, tumorigenicity behaves as a recessive genetic trait in pediatric cancers. Furthermore, different genetic elements may be lost during tumor development of adult cancers as opposed to pediatric cancers.

EMG Functional tasks recordings determines frailty phenotypes in males and females.

BACKGROUND: Identification of frailty is essential to understanding and mitigating age-related physical impairments. Previous studies have indicated that frailty phenotype can be identified through electromyography (EMG) when collected over the course of an 8-h day. However, long duration recordings challenge both the clinician and the older adults but activities of daily living that are most sensitive to changes in frailty status are currently unknown. The purpose of this study was to determine if muscle activity recorded during specific task, or groups of tasks, could be used to correctly classify middle-aged, non-frail, pre-frail, and frail older adult pheonotypes. METHODS: Fifteen middle-aged (49 ± 5 years) and 76 older adults (77 ± 8 years) participated. Older adults were categorized as non-frail (n = 49), pre-frail (n = 20), or frail (n = 7) using self-selected normal gait speed and a modified frailty index score. Bursts and gaps in EMG of the biceps brachii, triceps brachii, vastus lateralis, and biceps femoris were measured bilaterally during nine different functional tasks. RESULTS: Relatively high levels of success for frailty group classification (near 90%) can be achieved from EMG. Bursts were more frequent and gaps fewer in frail compared with middle-aged and non-frail adults. The numbers of gaps and muscle quiescence in the upper limbs were particularly important. Changes in muscle activity offer predictive value in identifying frailty phenotype. Completing functional tasks (rising from the floor, toilet and chair) while undergoing EMG assessment can contribute to the identification of differences in frailty phenotype among older adults.

The interaction between heparin and antithrombin III: a comparison of two different heparin-dye conjugates.

The interactions of antithrombin III with two heparin-dye conjugates have been compared using their fluorescence anisotropy. The first, heparin labelled with 5-isothiocyanatofluorescein, where the dye was mostly bound to unsulphated glucosamine residues, exhibited binding which was characteristic of heparin with a low affinity for antithrombin III. The second, heparin labelled with a reactive naphthalene dye (DENMT), showed similar binding character. However, when the heparin was treated with an amino group blocking agent prior to labelling with DENMT, the resultant heparin-dye conjugate showed binding behaviour, the strength of which was consistent with heparin molecules having both high and low affinity for antithrombin III. Heparin molecules with a high affinity for antithrombin III did not possess free amino groups. The implications of these findings are discussed with regard to the reliability of the data obtained using heparin-fluorescein conjugates.

A comparison of the strength of binding of antithrombin III, protamine and poly(L-lysine) to heparin samples of different anticoagulant activities.

The limiting concentrations, i.e., those concentrations of sodium chloride required to completely disrupt the complexes of heparin with antithrombin III, protamine and poly(L-lysine), were determined using fluorescence techniques, in order to compare the binding strengths of these complexes. From the limiting salt concentration values, poly(L-lysine) always exhibited stronger binding to heparin of a particular anticoagulant potency (degree of sulphation) than did protamine. The binding strengths of both complexes decreased as the degree of sulphation of the heparin participating in the complex was reduced. In contrast, the limiting salt concentration values for complexes formed between antithrombin III and heparin did not change with either the degree of sulphation or the biological potency of the heparin samples. A low-potency heparin simply contained a smaller number of molecules which possessed the intact antithrombin III binding site (thus being fully 'anticoagulant active') than a high-potency sample. Low-affinity heparin did not contain these binding sites and thus showed a low affinity for antithrombin III. High-potency heparin, being highly sulphated, possessed a higher affinity for protamine and poly(L-lysine) than for antithrombin III. However, after partial N-desulphation of heparin, the subsequent heparin-protamine complex was more weakly bound than a significant proportion of the corresponding heparin-antithrombin III complexes. These in vitro findings may have particular relevance in relation to the clinical condition termed 'heparin rebound'.