Allometric scaling of flow-mediated dilation: is it always helpful?

Flow-mediated dilation (FMD) is calculated as the greatest percent change in arterial diameter following an ischaemic challenge. This Traditional %FMD calculation is thought to have statistical bias towards baseline diameter (Dbase ), which is reduced by allometric scaling. This study examined whether allometric scaling FMD influenced the difference between a group of healthy young and older adults compared to the Traditional %FMD, and to determine whether a New (allometric) scaling %FMD improved the ability to obtain individually scaled FMD. Popliteal artery FMD was assessed in 18 young (26 ± 3 years) and 17 older adults (77 ± 5 years). 'Corrected' mean FMD was generated from a log-linked ANCOVA model. Individual %FMD was evaluated using three calculations: (1) Traditional %FMD calculation; (2) Atkinson (allometric) scaling %FMD (peak diameter (Dpeak)/(Dbasescalingexponent)); and (3) New scaling %FMD ((Dpeak-Dbase)/(Dbasescalingexponent)). Traditional %FMD was significantly larger in young (5·82 ± 2·58%) versus old (3·72 ± 1·26%). 'Corrected' FMD means (Y: 5·97 ± 2·12%; O: 3·98 ± 2·06%) were similar to Traditional %FMD; however, the logarithmic transformation prevents statistical interpretation of group differences. Individually scaled %FMD using the Atkinson scaling resulted in values that were corrected for variations in Dbase but that were twofold to threefold larger than those of the Traditional calculation. New scaling %FMD resulted in values that were similar to values expected (Y: 6·21 ± 2·75%; O: 3·98 ± 1·36%); however, it did not effectively correct for variation in Dbase . Recommendations regarding the advantages of allometrically scaling %FMD should be made with caution until research clearly establishes the benefits of this approach.

Immune-mediated cochleovestibular disease.

OBJECTIVE: The aim of this study is to prove the involvement of the immune response in the etiopathogenesis of some cochleovestibular disorders by a demonstration of antibodies against inner ear antigens and identify the benefits of immunosuppressive therapy. BACKGROUND: McCabe in 1979 postulated the hypothesis of autoimmune inner ear disease. METHODS: Sodium dodecyl sulfate polyacrylamid gel electrophoresis and immunoblotting were used to examine the serum of 74 subjects for the presence of antibodies against inner ear antigens. The subjects were divided into three groups: A--subjects with idiopathic progressive sensorineural hearing loss, B--subjects with Menière´s disease, C--healthy subjects. Individuals with proven antibodies received immunosuppressive therapy. RESULTS: We detected antibodies against inner ear antigens with molecular weight of 30, 50, 60, 80, 100 kDa. In group A they were found in 52% of 25 subjects, in group B in 44% of 25 subjects and they were not detected in group C. An improvement of hearing was recorded in 69% of subjects in group A. An improvement of hearing was observed in 72%, significant relief of vertigo in 81% of subjects in group B. CONCLUSION: The present study supports the hypothesis of immune-mediated cochleovestibular disease (Tab. 3, Ref. 15).

Obstetric conditions and the placental weight ratio.

INTRODUCTION: To elucidate how obstetric conditions are associated with atypical placental weight ratios (PWR)s in infants born: (a) ≥37 weeks gestation; (b) at ≥33 but <37 weeks gestation; and (c) <33 weeks gestation. METHODS: The study included all in-hospital singleton births in London, Ontario between June 1, 2006 and March 31, 2011. PWR was assessed as <10th or >90th percentile by gestational age-specific local population standards. Multivariable analysis was carried out using multinomial logistic regression with blockwise variable entry in order of temporality. RESULTS: Baseline factors and maternal obstetric conditions associated with PWR <10th percentile were: increasing maternal height, overweight and obese body mass indexes (BMI), large for gestational age infants, smoking, and gestational diabetes. Obstetric factors associated with PWR >90th percentile were: underweight, overweight and obese BMIs, smoking, preeclampsia, placenta previa, and placental abruption. In particular, indicators of hypoxia and altered placental function were generally associated with elevated PWR at all gestations. DISCUSSION: An association between obstetric conditions associated with fetal hypoxia and PWR ≥90th percentile was illustrated. CONCLUSIONS: The multivariable findings suggest that the PWR is similarly increased regardless of the etiology of the hypoxia.

[Orbital complications of sinusitis]. / Orbitálne komplikácie zápalov prínosových dutín.

Orbital complications categorised by Chandler are emergency. They need early diagnosis and agresive treatment. Stage and origin of orbital complications are identified by rhinoendoscopy, ophtalmologic examination and CT of orbite and paranasal sinuses. Periorbital cellulitis and early stage of orbital cellulitis can be treated conservatively with i. v. antibiotics. Monitoring of laboratory parameters and ophtalmologic symptoms is mandatory. Lack of improvement or worsening of symptoms within 24-48 hours and advanced stages of orbital complications are indicated for surgery. The purpose of the study is to evaluate epidemiology, clinical features and management of sinogenic orbital complications. Retrospective data of 8 patients with suspicion of orbital complication admited to hospital from 2008 to 2013 were evaluated. Patients were analyzed in terms of gender, age, CT findings, microbiology, clinical features, stage and treatment. Male and female were afected in rate 1,66:1. Most of patients were young adult in 3rd. and 4th. decade of life (62,5 %). Acute and chronic sinusitis were cause of orbital complication in the same rate. The most common origin of orbital complication was ethmoiditis (62,5 %), than maxillary (25 %) and frontal (12,5 %) sinusitis. Polysinusitis with affection of ethmoidal, maxillary and frontal sinuses (75 %) was usual CT finding. Staphylococcus epidermidis and Staphylococcus aureus were etiological agens in half of cases. Periorbital oedema (100 %), proptosis, chemosis (50 %), diplopia and glaucoma (12,5 %) were observed. Based on examinations, diagnosis of periorbital oedema/preseptal cellulitis was made in 3 (37,5 %), orbital cellulitis in 3 (37,5 %) and subperiosteal abscess in 2 cases (25 %). All patients underwent combined therapy - i. v. antibiotics and surgery within 24 hours. Eradication of disease from ostiomeatal complex (OMC), drainage of affected sinuses and drainage of subperiosteal abscess were done via fuctional endonasal endoscopic surgery (FEES). In case of superior subperiosteal abscess, combined endonasal and external approach (external orbitotomy) was needed. Combined therapy facilitated quick improvement of local and systematic symptoms. Average time of hospitalisation was 7 days. Early diagnosis and agresive combined therapy prevent loss of vision and life threatening complications.

Risk of kidney stones with surgical intervention in living kidney donors.

A kidney stone in a person with a solitary kidney requires urgent attention, which may result in surgical and/or hospital attention. We conducted a matched retrospective cohort study to determine if living kidney donors compared to healthy nondonors have a higher risk of: (i) kidney stones with surgical intervention, and (ii) hospital encounters for kidney stones. We reviewed all predonation charts for living kidney donations from 1992 to 2009 at five major transplant centers in Ontario, Canada, and linked this information to healthcare databases. We selected nondonors from the healthiest segment of the general population and matched 10 nondonors to every donor. Of the 2019 donors and 20 190 nondonors, none had evidence of kidney stones prior to cohort entry. Median follow-up time was 8.4 years (maximum 19.7 years; loss to follow-up <7%). There was no difference in the rate of kidney stones with surgical intervention in donors compared to nondonors (8.3 vs. 9.7 events/10 000 person-years; rate ratio 0.85; 95% confidence interval [CI] 0.47-1.53). Similarly there was no difference in the rate of hospital encounters for kidney stones (12.1 vs. 16.1 events/10 000 person-years; rate ratio 0.75; 95% CI 0.45-1.24). These interim results are reassuring for the safety of living kidney donation.

The role of vestibular evoked myogenic potentials (VEMPs) in vestibulopathy diagnostics.

OBJECTIVE: This study presents the role of vestibular evoked myogenic potentials (VEMPs) in the vestibular system investigation focused on the function of the saccule and inferior portion of the vestibular nerve. The main goal of the study is to report VEMP findings in different groups of patients with inner ear disorders symptoms and to identify some clinical application of this test in our patients. MATERIAL AND METHODS: WE have examined 218 patients with cochleovestibular symptomatology (sudden sensorineural cochlear hearing loss, retrocochlear hearing loss, vestibular neuronitis, benign paroxysmal positional vertigo (BPPV), Meniere´s disease, central vestibular disorder, as well as vertigo of non vestibular ethiology and 32 patients with conductive hearing loss with VEMP testing. We performed I channel and II channels measurements. RESULTS: We found no VEMP response in the group of conductive or mixed hearing loss in all cases - 100 % of 32 patients, in sudden sensorineural cochlear hearing loss in 35.4 % of 48 patients, in retrocochlear hearing loss in 19 % of 26 patients, in vestibular neuronitis in 40 % of 35 patients , in (BPPV) in 10 % of 43 patients, in Meniere´s disease in 61 % of 18 patients, in non vestibular vertigo in no case of 22 patients and in central vestibular disorders in 35 % of 23 patients. CONCLUSION: The present study shows the potential value of VEMP investigation in periferal vestibulopathy diagnosis (Tab. 1, Fig. 7, Ref. 33).

Cadmium, copper, iron, and zinc concentrations in kidneys of grey wolves, Canis lupus, from Alaska, Idaho, Montana (USA) and the Northwest Territories (Canada).

Cadmium, copper, iron, and zinc levels were measured in the kidneys of 115 grey wolves (Canis lupus) from Idaho, Montana and Alaska (United States), and from the Northwest Territories (Canada). No significant differences in the levels of iron or copper were observed between locations, but wolf kidneys from more northern locations had significantly higher cadmium levels (Alaska > Northwest Territories > Montana ≈ Idaho), and wolves from Alaska showed significantly higher zinc than other locations. Additionally, female wolves in Alaska had higher iron levels than males, and adult wolves in Montana had higher copper levels than subadults.

Hsp90 inhibitor geldanamycin increases the sensitivity of resistant ovarian adenocarcinoma cell line A2780cis to cisplatin.

Ovarian carcinoma is the leading cause of death among gynecological neoplasms in the world. The chemoresistance is a major obstacle in the effective treatment of ovarian and other cancers. We evaluated the effects of Hsp90 inhibitor geldanamycin (GEL) alone and in combination with cisplatin in cisplatin resistant ovarian adenocarcinoma cell line. Our results showed Akt depletion and S-phase arrest of A2780cis cells after GEL treatment. Combined exposure of A2780cis cells to GEL and cisplatin resulted in greater than additive cytotoxic effect.

Influential observations in weighted analyses: examples from the National Longitudinal Survey of Children and Youth (NLSCY).

This paper highlights the impact of survey weights on model fit in multiple linear regression with specific reference to the National Longitudinal Survey of Children and Youth (NLSCY) and provides recommendations for the treatment of influential observations. Multiple linear regression was used to estimate the association between child and family factors in the preschool years and vocabulary development at school age. Analyses were performed with and without survey weights. The model fit was assessed by examining the distribution of the studentized residuals and the change in the regression coefficients that would occur if an observation were removed. Two summary measures of influence, Dffits and Cook's D are reported. The models were refit excluding influential observations. Weighting of the linear model resulted in previously non-influential observations having an undue influence on the estimation of the regression parameters in the weighted model. The influential observations were driven primarily by the size of the survey weight as opposed to unusual values of x and y. Researchers working with large national health surveys such as the NLSCY and the National Population Health Survey (NPHS) are advised to include a detailed influence analysis before any final conclusions are made.

Blunt external trauma to the trachea: report of two cases.

We present two cases of blunt external trauma to the trachea. The first was a 19-year-old man who had suffered rupture of the first tracheal ring as a consequence of attempting suicide by hanging from a cable. The second was an 11-year-old boy who fell from a bicycle and struck his neck against the handlebars. Fracture of the second tracheal ring was found at surgery. Both cases were treated by primary repair. A surgical exploration is essential in the case of subcutaneous emphysema, even if no respiratory distress is present and a radiological evaluation is negative. Follow up, according to the extent and type of injury, is recommended to prevent post traumatic stenosis of the trachea.

[Surgical correction of lagophthalmos by implantation of a gold weight]. / Chirurgická úprava lagoftalmu implantáciou zlatého závazia.

This study concerns the problematics of upper branch of n. VII rehabilitation. Surgical technique is presented which involves implantation of gold weight into the upper eyelid which was used in 17 patients. The study emphasizes importance of oculoplastic surgery which should become an integral part of management of facial nerve paresis.

Comprehensive tobacco control policies and the smoking behaviour of Canadian adults.

OBJECTIVE: To examine the associations of cigarette prices, restrictions on public smoking, and health education with the odds of adult smoking and amount smoked daily. DESIGN: Multi-level analysis of adult (age 25+) smoking patterns in Canada's National Population Health Survey, after adding administrative data on prices, bylaws, and health education according to the survey respondent's place of residence. SETTING/SUBJECTS: Population based sample of Canadians age 25+ in households (n = 14 355). OUTCOME MEASURES: Smoking status, amount consumed daily. ANALYSIS: Logistic regression for smoking status, multiple regression for amount smoked, with controls for age, education, marital status; separate analyses for men and women. RESULTS: Cigarette prices were positively associated with the odds of being a non-smoker and negatively with amount smoked, for adults of both sexes. Per capita health education expenditures were positively associated with the odds of being a non-smoker and negatively with amount smoked--for men but not women. The restrictiveness of municipal bylaws limiting public smoking was positively associated with the odds of being a non-smoker and negatively with amount smoked--for women but not men. These results are independent of age, education, and marital status. CONCLUSIONS: To be effective, tobacco control must comprise a mix of strategies as men and women respond differently to health education and restrictions on public smoking; taxation, reflected in higher cigarette prices, is the only one of these measures related to smoking for both sexes. This model permits calculations of the level of increase in each measure that is required to reduce the prevalence of smoking by a specified amount.

Lung function in older humans: the contribution of body composition, physical activity and smoking.

An allometric model was used to determine the important factors related to the decline in forced expiratory volume (FEV1.0) across ages 55-86 years in independently living men and women. Measurements were available from a randomized sample of 181 men and 203 women residing in London, Ontario, Canada. The effects of height, age, sex, adiposity, fat free mass (FFM), grip strength and physical activity (PA) on FEV1.0 were assessed using an allometric model to test the hypothesis that sex differences in lung function would be due in part to sex-related differences in the aforementioned variables and would therefore be eliminated by our analysis. The following model was linearized and parameters were identified using standard multiple regression: FEV1.0 = height(beta1) x FFM(beta2) x grip strength(beta3) x PA(beta4) x exp(beta0 + beta5age + beta6sex + beta7smoking + beta8%body fat) x epsilon. Results indicate that the amount of FFM and heavy intensity physical activity participated in by the elderly may be more important in influencing forced expiratory function than previously recognized. In addition, results from this study have confirmed the importance of age and height in the prediction of FEV1.0 and demonstrated a negative effect of smoking on lung function. Individuals with a greater FFM and physical activity level tended to be associated with an above average lung function performance. The cross-sectional rate of decline in FEV1.0 determined from our model was approximately 12% per decade.

The influence of falling, fear of falling, and balance confidence on prosthetic mobility and social activity among individuals with a lower extremity amputation.

OBJECTIVE: To assess in amputee patients the relationship between having fallen in the past 12 months, fear of falling, and balance confidence on mobility capability, mobility performance, and social activity. DESIGN: Population-based survey and chart review. SETTING: Two university-affiliated outpatient amputee programs in southwestern Ontario. PARTICIPANTS: Community-living individuals (n = 435) with a unilateral lower limb amputation. INTERVENTIONS: Patient chart review and a survey questionnaire. MAIN OUTCOME MEASURES: Self-report assessment of prosthetic capability and performance and social activity participation was assessed with the Prosthetic Evaluation Questionnaire mobility subscale, the Houghton Scale, and the Frenchay Activities Index. RESULTS: Falling experiences in the past 12 months were not significantly associated with any outcomes. Fear of falling was important in univariate relationships in all 3 outcomes, but not when balance confidence was included in multivariable modeling. Balance confidence was statistically significant with each of the outcomes and remained significant with inclusion of the covariates. There was statistical interaction (balance confidence x automatism; balance confidence x medication count) in modeling mobility capability and in modeling mobility performance (balance confidence x pain + balance confidence x amputation level). The final models accounted for 70%, 60%, and 55% of the variation in mobility capability, mobility performance, and social activity, respectively. CONCLUSION: Balance confidence was the only factor associated with mobility capability and performance and social activity in the final adjusted models. Clinicians and researchers should consider this variable in the rehabilitation of amputee patients.

A self-paced step test to predict aerobic fitness in older adults in the primary care clinic.

OBJECTIVES: To study the potential usefulness of a submaximal self-paced step test as a prediction of maximal aerobic capacity (VO2max) in older adults in the primary care setting. DESIGN: Data were collected during a prospective randomized study of an exercise program. SETTING: Four university family medical clinics in London, Ontario, Canada. PARTICIPANTS: A random sample of 240 healthy older (> or =65) men (n = 118) and women (n = 122) from four family medical clinics underwent self-paced step testing in the clinic with a family physician (n = 16), and step testing and a maximal exercise treadmill test with measurement of respired gases in an exercise laboratory. Testing was done in random order (clinic/laboratory) separated by 2 weeks and then repeated at 52 weeks, following introduction of an exercise program. Relationships between outcome variables were examined by Pearson correlation coefficients while prediction of VO2max was examined using multivariate regression analysis. Cross-validation with 30 age-matched hypertensive and 40 age-matched post-hip arthroplasty patients was used to test the accuracy of the predictive models. MEASUREMENTS: Measured VO2max, predicted VO2max, step test time, step test heart rate, body mass index (BMI), and O2 pulse. RESULTS: Two hundred women (n = 108) and men (n = 92) completed both the initial and 52-week assessments. Stepping time, heart rate, age, BMI, and O2 pulse were strongly associated with VO2max for both a normal and a fast step pace and were chosen to develop the predictive model. Normal step-pace correlation with VO2max (ml/kg/min) was no different (female 0.93: male 0.91) from fast pace (0.95:0.90) with no difference between clinic and laboratory measurement at baseline or 52 weeks. Cross-validation showed no significant difference from the main group using the predictive model. CONCLUSIONS: The self-paced step test is a safe and simple clinical instrument that strongly and reliably predicts VO2max, is sensitive to change, and is generalizable in the family practice setting among community-dwelling older adults differing in fitness and health status.

Exercise increases hexokinase II mRNA, but not activity in obesity and type 2 diabetes.

Glucose phosphorylation, catalyzed by hexokinase, is the first committed step in glucose uptake in skeletal muscle. Hexokinase II (HKII) is the isoform that is present in muscle and is regulated by insulin and muscle contraction. Glucose phosphorylation and HKII expression are both reduced in obese and type 2 diabetic subjects. A single bout of exercise increases HKII mRNA and activity in muscle from healthy subjects. The present study was performed to determine if a moderate exercise increases HKII mRNA expression and activity in patients with type 2 diabetes. Muscle biopsies were performed before and 3 hours after a single bout of cycle ergometer exercise in obese and type 2 diabetic patients. HKII mRNA and activity and glycogen synthase activity were determined in the muscle biopsies. Exercise increased HKII mRNA in obese and diabetic subjects by 1.67 +/- 0.34 and 1.87 +/- 0.26-fold, respectively (P <.05 for both). Exercise did not significantly increase HKI mRNA. When HKII mRNA increases were compared with the 2.26 +/- 0.36-fold increase in HKII mRNA previously reported for healthy lean subjects, no statistically significant differences were found. In contrast to the increase in HKII activity observed after exercise by lean healthy controls, exercise did not increase HKII activity in obese nondiabetic or diabetic subjects. Exercise increased glycogen synthase activity (GS(0.1) and GS(FV)) significantly in both obese nondiabetic and type 2 diabetic patients. The present results indicate that there is a posttranscriptional defect in the response of HKII expression to exercise in obese and type 2 diabetic subjects. This defect may contribute to reduced HKII activity and glucose uptake in these patients.

Is smoking associated with the risk of developing Alzheimer's disease? Results from three Canadian data sets.

PURPOSE: To determine whether smoking is associated with Alzheimer's disease (AD). METHODS: Analyses were conducted using three Canadian data sets: the University of Western Ontario Dementia Study (200 cases, 163 controls), the Canadian Study of Health and Aging (258 cases, 258 controls), and the patient database from the Clinic for Alzheimer Disease and Related Disorders at the Vancouver Hospital and Health Sciences Centre (566 cases, 277 controls). The association between smoking and AD was investigated using bivariate analyses and multiple logistic regression models adjusted for the potential confounders age, sex, educational level, family history of dementia, head injury, and hypertension. RESULTS: The results of bivariate analyses were inconsistent across the three data sets, with smoking status a significant protective factor, a significant risk factor, or not associated with AD. The results of multiple logistic regression models, however, were consistent: any association between smoking status and AD disappeared in all three data sets after adjustment for confounders. CONCLUSIONS: Smoking status was consistently not associated with AD across all three data sets after adjustment for confounders. Failure to adjust for relevant confounders may explain inconsistent reports of the influence of smoking on AD. Any protective effect of smoking may be limited to specific AD subtypes (e.g., early onset AD).

Periodicity of arrhythmias in healthy elderly men at the moderate altitude.

The 24-hour periodicity of supraventricular (SVPB) and ventricular (VEB) extrasystoles in healthy elderly men (age 49-69 years) was studied at two altitudes during 24 h Holter ECG monitoring. At the low altitude (200 m, n = 26), SVPB were more frequent than VEB. The highest occurrence of SVPB was at 17:00 h, the lowest at 01:00 and 02:00 h (P<0.001). The highest occurrence of VEB was at 09:00 h, the lowest one at 04:00 h (P<0.001). At 1350 m (n=9) the incidence of both SVPB and VEB was approximately twofold higher compared to that at the low altitude (P<0.001). The highest occurrence of SVPB was at 13:00 h, the lowest at 06:00 h (P<0.001). VEB were the most frequent at 10:00 h and 13:00 h, while the lowest frequency was observed at 06:00 h (P<0.001). Our results indicate that the incidence of SVPB and VEB in healthy persons at the moderate altitude is twofold and its periodicity is shifted compared to the low altitude. The cause of increased occurrence of extrasystoles is probably due to beta-adrenergic activation of the heart at the higher altitude.

Models of the relationship of stress, depression, and other psychosocial factors to smoking behavior: a comparison of a cohort of students in grades 6 and 8.

BACKGROUND: Six specific hypotheses regarding putative mechanisms by which stressful life events might lead to initiation of smoking among adolescents were proposed and tested on a Grade 6 cohort of students in Scarborough, Ontario, Canada. In addition, the data were used to determine the set of risk factors for initiation of smoking most pertinent to the experience of the cohort. METHODS: The same relationships were examined for the 1,543 students when they were in Grade 8 and compared to the earlier Grade 6 results. The hypotheses include the effects of personal resources (coping, self-esteem, social support, and mastery), social conformity, rebelliousness, attitudes, smoking environment factors, and gender differences. RESULTS: The hypotheses were not unequivocally supported, except for the hypotheses about attitudes and smoking environment as well as gender effects. Males and females differ with regard to the variables and interrelationships in both years and in the final models developed. In Grade 6, there are more smoking environment items for males than for females. By Grade 8, male smoking is influenced by mastery, social conformity, and rebelliousness, while for females environmental smoking and rebelliousness are important. CONCLUSION: Male and female students differ in how stress, depression, and smoking are related in the presence of psychosocial factors.

Regulation of hexokinase II expression in human skeletal muscle in vivo.

The phosphorylation of glucose to glucose-6-phosphate (G-6-P) is the first committed step in glucose uptake in skeletal muscle. This reaction is catalyzed by hexokinase (HK). Two HK isoforms, HKI and HKII, are expressed in human skeletal muscle, but only HKII is regulated by insulin. The present study was undertaken to determine the time course for the regulation of HK activity and expression by physiological plasma insulin concentrations in human skeletal muscle in vivo. A hyperinsulinemic-euglycemic glucose clamp and percutaneous muscle biopsy were performed in separate groups of healthy subjects after 60, 120, 180, and 360 minutes of euglycemic hyperinsulinemia. Muscle biopsies were subfractionated into soluble and particulate fractions to determine HKI and HKII activities. RNA was extracted from a separate portion of the muscle biopsy, and HKI and HKII mRNA content was determined using an RNase protection assay. Glycogen synthase (GS) activity and fractional velocity were also determined. HKII mRNA was increased 2-fold by 120 minutes and remained high versus the basal value for up to 360 minutes. HKI mRNA was unchanged throughout the study. HKII activity increased after 360 minutes of insulin infusion, and this increase was limited to the soluble fraction. In contrast, insulin induced a 1.5- to 2-fold increase in GS fractional velocity that was sustained for 360 minutes. The time course of the ability of hyperinsulinemia to increase HKII mRNA indicates that insulin is likely a physiological regulator of HKII expression in human skeletal muscle in vivo.