Evaluation of augmented reality training for a navigation device used for CT-guided needle placement.

PURPOSE: Numerous navigation devices for percutaneous, CT-guided interventions exist and are, due to their advantages, increasingly integrated into the clinical workflow. However, effective training methods to ensure safe usage are still lacking. This study compares the potential of an augmented reality (AR) training application with conventional instructions for the Cube Navigation System (CNS), hypothesizing enhanced training with AR, leading to safer clinical usage. METHODS: An AR-tablet app was developed to train users puncturing with CNS. In a study, 34 medical students were divided into two groups: One trained with the AR-app, while the other used conventional instructions. After training, each participant executed 6 punctures on a phantom (204 in total) following a standardized protocol to identify and measure two potential CNS procedural user errors: (1) missing the coordinates specified and (2) altering the needle trajectory during puncture. Training performance based on train time and occurrence of procedural errors, as well as scores of User Experience Questionnaire (UEQ) for both groups, was compared. RESULTS: Training duration was similar between the groups. However, the AR-trained participants showed a 55.1% reduced frequency of the first procedural error (p > 0.05) and a 35.1% reduced extent of the second procedural error (p < 0.01) compared to the conventionally trained participants. UEQ scores favored the AR-training in five of six categories (p < 0.05). CONCLUSION: The AR-app enhanced training performance and user experience over traditional methods. This suggests the potential of AR-training for navigation devices like the CNS, potentially increasing their safety, ultimately improving outcomes in percutaneous needle placements.

Elevated alanine aminotransferase independently predicts new onset of depression in employees undergoing health screening examinations.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated alanine aminotransferase (ALT). NAFLD is associated with insulin resistance and hepatic inflammation. Similarly, patients with depression exhibit insulin resistance and increased inflammatory markers. However, no study has shown a clear association between elevated ALT and the development of depression. The aim of the study was to test whether elevated ALT, a surrogate marker for NAFLD, predicts the development of depression. METHOD: The present prospective cohort study investigated 12 180 employed adults referred for health examinations that included fasting blood tests and anthropometric measurements between 2003 and 2010. Exclusion criteria were: baseline minor/major depression, excessive alcohol consumption and other causes for ALT elevation. Depression was evaluated by the eight-item Patient Health Questionnaire (PHQ-8) score. RESULTS: The final cohort included 5984 subjects [69.4% men, aged 45.0 (s.d. = 10.24) years]. The incidence rate of minor and major depression was 3.8% and 1.4%, respectively. Elevated ALT was a significant independent predictor for the occurrence of minor [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.40-2.92] and major (OR 3.132, 95% CI 1.81-5.40) depression after adjusting for age, gender, body mass index, education level, serum levels of lipids, glucose, smoking and physical activity. Adding subjective health and affective state parameters (sleep disturbances, self-rated health, anxiety and burnout) as potential mediators only slightly ameliorated the association. Persistently elevated ALT was associated with the greatest risk for minor or major depression as compared with elevation only at baseline or follow-up (p for trend < 0.001). CONCLUSIONS: Elevated ALT was associated with developing depressive symptoms, thus suggesting that NAFLD may represent an independent modifiable risk factor for depression.

Assessment of high-sensitivity CRP as a marker of micro-inflammation in irritable bowel syndrome.

BACKGROUND: The diagnosis of irritable bowel syndrome (IBS) is symptom-based. Although considered a functional disease, accumulating evidence supports a low-grade gut inflammation as an element of its pathophysiology. Thus, high-sensitivity C-reactive protein (hs-CRP), a marker of micro inflammation, may be elevated in IBS. Our aim was to assess whether hs-CRP is higher in IBS patients compared to healthy controls (HC) and does it differ among the IBS clinical subgroups and correlate with disease severity. METHODS: A diagnostic case control study was conducted in two gastroenterology departments. Eighty-eight IBS patients who were recruited prospectively answered the Rome III diagnostic questionnaire. They all completed the Functional Bowel Disorder Severity Index (FBDSI), dietary, and general health questionnaires. All patients underwent blood sampling for hs-CRP levels. Each IBS patient was matched to four HC by age, gender, and BMI. Blood samples were obtained from the HC at a periodic health survey. KEY RESULTS: The mean hs-CRP level in the IBS group was significantly higher than in HC (1.17±1.26mg L(-1) vs 0.72±0.91mg L(-1) respectively, P=0.001). Hs-CRP levels were highest in patients with diarrhea-predominant IBS and in patients with greater disease severity. A cut-off value of 1.08mg L(-1) had a sensitivity of 60.2% and a specificity of 68% for differentiating IBS from HC. CONCLUSIONS & INFERENCES: Hs-CRP levels are higher in IBS patients than HC, but still in the normal laboratory range. This may reflect the low-grade gut inflammation believed to occur in IBS and support its existence.

Optical and electrical interfacing technologies for living cell bio-chips.

Whole-cell bio-chips for functional sensing integrate living cells on miniaturized platforms made by micro-system-technologies (MST). The cells are integrated, deposited or immersed in a media which is in contact with the chip. The cells behavior is monitored via electrical, electrochemical or optical methods. In this paper we describe such whole-cell biochips where the signal is generated due to the genetic response of the cells. The solid-state platform hosts the biological component, i.e. the living cells, and integrates all the required micro-system technologies, i.e. the micro-electronics, micro-electro optics, micro-electro or magneto mechanics and micro-fluidics. The genetic response of the cells expresses proteins that generate: a. light by photo-luminescence or bioluminescence, b. electrochemical signal by interaction with a substrate, or c. change in the cell impedance. The cell response is detected by a front end unit that converts it to current or voltage amplifies and filters it. The resultant signal is analyzed and stored for further processing. In this paper we describe three examples of whole-cell bio chips, photo-luminescent, bioluminescent and electrochemical, which are based on the genetic response of genetically modified E. coli microbes integrated on a micro-fluidics MEMS platform. We describe the chip outline as well as the basic modeling scheme of such sensors. We discuss the highlights and problems of such system, from the point of view of micro-system-technology.

A 1-year study to compare the efficacy and safety of once-daily travoprost 0.004%/timolol 0.5% to once-daily latanoprost 0.005%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: The objective of the study was to compare the intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004%/timolol 0.5% ophthalmic solution (Trav/Tim) to latanoprost 0.005%/timolol 0.5% ophthalmic solution (Lat/Tim), dosed once daily in the morning, in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). METHODS: This was a randomized, double-masked, multicenter, parallel group, active-controlled study conducted at 41 sites. At the eligibility visit the patients were randomized (1:1) to the assigned masked medication if they met inclusion/exclusion criteria, and the mean IOP values in the eligible eyes were > or =24 mmHg at 9 AM and > or =21 mmHg at 11 AM and 4 PM. Patients were excluded if the mean IOP in either eye was >36 mmHg. Patients were instructed to administer the assigned medication each morning at 9 AM. During the treatment phase of the study, IOP was measured at 9 AM at week 2, week 6, month 3, and month 9. At the month 6 and month 12 visits, IOP was measured at 9 AM, 11 AM, and 4 PM. Statistical methods included a repeated measures analysis of variance (ANOVA); to test for noninferiority, a 95% confidence interval for the treatment group difference was constructed based on the ANOVA results for each time point at month 12. RESULTS: Patients (n=408) with OAG or OH were enrolled at 41 sites. One patient withdrew prior to receiving medication so 207 in the Trav/Tim group and 200 in the Lat/Tim group were evaluable for safety. Baseline demographic characteristics as well as IOP values showed no statistical differences between the two groups. Trav/Tim provided lower mean IOP values than Lat/Tim that were statistically significant at the week 2 9 AM (p=0.0081), month 6 9 AM (p=0.0056), and month 6 11 AM (p=0.0128) time points and at 9 AM time point pooled across all visits (p=0.0235) when mean IOP was 0.6 mmHg lower in the Trav/Tim group. Treatment-related adverse events were mild in both groups. Although hyperemia was reported from a higher percentage of patients in Trav/Tim group, differences in average hyperemia scores between the two groups were not considered clinically relevant. CONCLUSIONS: Travoprost 0.004%/timolol 0.5% ophthalmic solution produced mean IOP levels that are statistically noninferior to latanoprost 0.005%/timolol 0.5% ophthalmic solution. Furthermore, at 9:00 AM, 24 hours after dosing, IOP was statistically lower for travoprost 0.004%/timolol 0.5% pooled across all visits. Travoprost 0.004%/timolol 0.5% fixed combination ophthalmic solution is an effective treatment for reducing IOP and it is safe and well-tolerated in patients with OAG or OH.

Heart rate and microinflammation in men: a relevant atherothrombotic link.

OBJECTIVE AND BACKGROUND: To explore the possibility that increased resting heart rate (HR) is associated with a microinflammatory response. Such an association could explain, at least in part, the recently described worse cardiovascular prognosis in individuals with increased HR. METHODS: Concentrations of fibrinogen and high-sensitivity C-reactive protein, as well as the absolute number of polymorphonuclear leucocytes, were analysed in a cohort of 4553 apparently healthy men and in those with atherothrombotic risk factors. RESULTS: Following adjustment for age and body mass index, lipid profile and cardiovascular risk factors, a significant (p<0.001) difference was noted between individuals in the first quintile of HR (< or =58 beats/min) and those in the fifth quintile (> or =79 beats/min) regarding all the above-mentioned inflammatory biomarkers, the respective mean values being 7.38 and 8.11 micromol/l, 1.12 and 1.61 mg/l, and 4.23 and 4.74 x 10(9)/l. CONCLUSIONS: Resting HR is associated with a microinflammatory response in apparently healthy men and in those with atherothrombotic risk factors. Sympathetic activation might be a common factor explaining such an association. If confirmed in additional studies, this association might be a relevant target for therapeutic manipulations.

Diurnal IOP control with bimatoprost versus latanoprost in exfoliative glaucoma: a crossover, observer-masked, three-centre study.

AIM: To evaluate the diurnal intraocular pressure (IOP) control and safety of bimatoprost versus latanoprost in exfoliative glaucoma (XFG). METHODS: One eye of 129 consecutive patients with XFG (mean (SD) age 66.5 (8.3) years) was included in this prospective, observer-masked, three-centre, crossover comparison. After a 4-6 week medicine-free period patients were randomised to bimatoprost or latanoprost monotherapy for 3 months. Patients were then switched to the opposite treatment for another 3 months. At the end of the washout and the treatment periods diurnal IOP was measured at 0800, 1300, and 1800. RESULTS: At baseline the IOP (mean (SD)) was 28.0 (4.0), 26.9 (3.6), and 25.9 (3.6) mm Hg, at the three time points, respectively. Both treatments significantly reduced mean diurnal IOP at month 3. Mean diurnal IOP was 26.9 (3.5) mm Hg at baseline, 17.6 (3.3) mm Hg with bimatoprost, and 18.6 (3.6) mm Hg with latanoprost (p<0.0001). Furthermore, lower IOP values were obtained with bimatoprost at all time points (17.9 (3.4), 17.3 (3.3), and 17.6 (3.5) mm Hg, respectively) compared with latanoprost (18.7 (3.6), 18.5 (3.6), and 18.6 (4.1) mm Hg, respectively). The corresponding mean differences (0.8, 1.1, and 1.0 mm Hg, respectively) were all significant (p<0.001 for each comparison). Significantly more patients with XFG obtained a target diurnal IOP <17 mm Hg with bimatoprost than with latanoprost, 55/123 (45%) v 34/123 (28%); (p = 0.001), and significantly fewer patients were non-responders with bimatoprost than with latanoprost (5 v 13, p = 0.021). More patients reported at least one adverse event with bimatoprost than with latanoprost (58 v 41 at 3 months; p = 0.0003). CONCLUSION: This crossover study suggests that better diurnal IOP control is obtained with bimatoprost than with latanoprost in patients with XFG.

Skin test results and self-reported symptom severity in allergic rhinitis: The role of psychological factors.

BACKGROUND: In allergic conditions, the degree of skin test reactivity does not always correlate with the severity of clinical symptoms. Additional factors may contribute to the reported symptom severity. OBJECTIVES: To investigate the association between the magnitude of the skin prick test (SPT) response and the reported symptom severity in patients with allergic rhinitis and the possible modifying role of psychological factors. METHODS: One hundred four patients with allergic rhinitis and 23 with non-allergic rhinitis, classified according to their SPT response to 19 aeroallergens, were asked to rate the severity of five symptoms and to indicate whether their symptoms intensified on exposure to five common aeroallergens. They also completed a psychological questionnaire. Results Reported symptom severity of allergic rhinitis did not correlate with weal size for any of the aeroallergens tested or with the number of positive responses on SPT. It was not related to patient age, sex, or education. The reported symptoms severity correlated positively (0.29, P < 0.01) with reported symptom intensification on exposure to allergens. Moreover, both outcomes were positively associated with the psychological factors of hypochondriasis (0.20, P < 0.05 and 0.18, P < 0.05, respectively), and somatic awareness (0.24, P < 0.05 and 0.33, P < 0.01, respectively), but not with neuroticism. CONCLUSIONS: The severity of symptoms experienced by patients with allergic rhinitis is apparently not related to the magnitude of SPT response, but rather to psychological factors of hypochondriasis and somatic awareness. Physicians should be aware of the contribution of psychological factors to patient perceptions of the intensity of symptoms and of the intensification of symptoms on their exposure to allergens.

Increased erythropoiesis and subclinical inflammation as part of the metabolic syndrome.

Recent studies have suggested the insulin resistance might be accompanied by enhanced erythropoiesis. We have examined this association in individuals with the metabolic syndrome (MS) who in addition to insulin resistance harbor a chronic low grade inflammation. This study is relevant because chronic inflammation might have a suppressive effect on erythropoiesis. 280 and 554 non-smoking women and men with respective age of 46.4+/-9.3 (mean+/-S.D.) and 44.0+/-11.0 years are included. A significant correlation was noted between the numbers of the components of the MS and the inflammatory biomarkers including the white blood cell count, high sensitivity C-reactive protein, fibrinogen concentrations and the erythrocyte sedimentation rate. In addition, a significant correlation (r=0.157, p=0.008) was noted between the number of components of the MS and the number of red blood cells in the peripheral blood in women. The same was true for men (r=0.192, p<0.0005). We conclude that enhanced erythropoiesis could be a new, hitherto unrecognized component of the MS. The enhanced erythropoiesis could give an erroneous impression of general "good" health in these individuals.

Obesity-related correlation between C-reactive protein and the calculated 10-y Framingham Coronary Heart Disease Risk Score.

OBJECTIVE: To clarify the role of body mass index (BMI, kg/m(2)) adjustment in predictive models for cardiovascular events that add high-sensitivity C-reactive protein (hs-CRP) to the 10-y Framingham Coronary Heart Disease Risk Score (FCRS). DESIGN: A cross-sectional study in a group of apparently healthy individuals. SUBJECTS: In all, 1512 apparently healthy individuals (955 men and 557 women) at a respective age of 49.7+/-10.6 and 50.6+/-9.6 y. RESULTS: The Pearson correlation between hs-CRP and the calculated 10-y FCRS was lower when adjusted for BMI. This reduction was especially noted in women where it dropped from 0.247 to 0.09. The dominant role of hs-CRP concentrations was also noted in a linear regression model, again, especially noted in women (drop of the standardized coefficient from 0.517 for BMI to 0.08 for the FCRS). CONCLUSIONS: The correlation between hs-CRP and the 10-y FCRS is partly related to the presence of obesity. We raise the possibility that the addition of BMI to the predictive model of FCRS might attenuate the cost-effectiveness of CRP measurements for this specific risk assessment.

Oral temperature in daily life. A new look in the era of microinflammation.

It has been repeatedly shown that apparently healthy individuals and those with atherothrombotic risk factors harbor a low grade subclinical internal inflammation (microinflammation). This low grade acute phase response is relevant for the presence of atherothrombosis and future vascular events. Since these events are associated with a febrile response, we thought that it is relevant to clarify whether the microinflammatory response has an influence on the oral temperature. Included were 2,340 men and 1,280 women in whom the white blood cell count (WBCC) and differential, as well as the erythrocyte sedimentation rate (ESR), quantitative fibrinogen and high sensitivity C-reactive protein (hs-CRP) were determined in addition to the oral temperature in quiescent conditions. There was no association between these inflammatory biomarkers, except from a weak association with the absolute number of polymorphonuclear leukocytes. This association could be, however, related to the stress of the examination itself. Thus, it is unlikely that the microinflammatory response in daily life is associated, to a significant degree, with an enhanced oral temperature. The results are relevant for the findings of elevated oral temperature during conditions of acute ischemia/infarction where the temperature is probably related to the event itself and not to the patient's background microinflammation.

Pingelapese achromatopsia: correlation between paradoxical pupillary response and clinical features.

AIM: To evaluate the paradoxical pupillary constriction in darkness in patients with Pingelapese achromatopsia (PA), and to describe a connection between this phenomenon and the clinical features. METHODS: 27 patients with PA were examined. All underwent a full ophthalmic examination which included Snellen visual acuity and ophthalmoscopy. Colour vision examination was performed with Ishihara pseudoisochromatic plates and also with a colour plate consisting of five basic colours (red, green, purple, yellow, and orange). Paradoxical pupillary response was examined and documented with a special infrared video camera. Pupils' images were analysed using the Scion Image program and the ratio of pupil size in darkness to its size in light was calculated and recorded. RESULTS: Mean visual acuity was 20/400 (range 20/80-20/800). Colour vision examination showed a mean of 3.2 (SD 1.5) (range 1-5) of Ishihara colour plates, and 0.5 (0.75) (0-3) of basic colour plates. 23 patients (85%) had paradoxical pupillary constriction in darkness. Mean dark/light ratio of pupillary area was 0.86 (range 0.5-1.6). In patients with marked paradoxical pupillary constriction there was a significant correlation of visual acuity and Ishihara score. CONCLUSIONS: Clinical manifestations of achromatopsia include total colour blindness, low visual acuity (mean of 20/400), horizontal pendular or rotatory nystagmus, and photophobia. Most patients have paradoxical pupillary constriction in darkness. When this response is brisk it seems to correlate with lower visual acuity and lower Ishihara score.

Neuroprotective properties of a synthetic docosanoid, unoprostone isopropyl: clinical benefits in the treatment of glaucoma.

The characteristic loss of visual field due to glaucoma is directly associated with retinal ganglion cell (RGC) death. The process of RGC death is thought to be biphasic, starting with a primary injury, followed by a slow secondary degeneration. Retinal ischemia may establish the cellular conditions that create a fatal biochemical cascade; hypoxia, followed by high excitotoxic levels of glutamate cause pathologically elevated levels of intracellular calcium resulting in neuronal cell death via apoptosis or necrosis. Impaired ocular perfusion, primarily due to abnormal autoregulation and/or vasoconstriction caused by endothelin-1, probably contributes to the ischemic milieu. Neuroprotection, the preservation of neurons that were either not damaged or only slightly damaged during the primary insult, has become important for the clinician when considering treatment options. Unoprostone, the first synthetic docosanoid, has been demonstrated to exhibit neuroprotective properties. In an ischemic animal model, unoprostone protected RGCs in a dose-dependent manner. Unoprostone inhibits glutamate stimulation and opens maxi-K channels, which are potassium channels that reach an activation threshold only during depolarization and/or at high intracellular Ca2+ concentrations. The resultant large efflux of K+ hyperpolarizes the cell, thereby closing voltage-gated Ca2+ channels and limiting neuronal damage by decreasing influx of intracellular Ca2+. Unoprostone has also been shown to protect rat photoreceptors from constant light-induced damage. Lastly, unoprostone has vasorelaxant properties, evidenced by increased choroidal blood flow and inhibition of vasoconstrictors such as endothelin-1. These findings indicate that a substantial clinical benefit of unoprostone is neuroprotection of RGCs.

The interactive effect of chronic exposure to noise and job complexity on changes in blood pressure and job satisfaction: a longitudinal study of industrial employees.

The hypothesis of this study was that noise exposure level and job complexity interact to affect changes in blood pressure (BP) levels and job satisfaction over 2-4 years of follow-up. Results showed that among workers exposed to high noise, those with complex jobs showed increases in BP that were more than double shown by those with simple jobs. Under low noise exposure, there was a small increase in BP for workers with complex jobs but about a 3-fold increase in workers with simple jobs. The prevalence of elevated BP showed a similar trend. Job satisfaction increased among workers with complex jobs but was much less in those exposed to high noise. It was concluded that exposure to occupational noise has a greater negative impact on changes in BP and job satisfaction over time among those performing complex jobs. In contrast, job complexity had a clear beneficial effect for workers exposed to low noise.

Low job satisfaction predicts delayed return to work after laparoscopic cholecystectomy.

We studied 102 consecutive employed patients treated by elective laparoscopic cholecystectomy to determine job characteristics and psychological factors that predict delay in return to work after their procedure. Median sick leave was 13 days, and five variables significantly added to a model predicting sick leave of at least 20 days (31.4% of the workers): low job satisfaction (odds ratio [OR], 12.56; 95% confidence interval [CI], 3.34 to 47.2); physical effort at work (OR, 4.99; 95% CI, 1.46 to 17.04); pain at 7 days (OR, 5.55; 95% CI, 1.56 to 19.76); patient's expectation of slow recovery (> 7 days) (OR, 6.12; 95% CI, 1.82 to 20.55); and patient's expectation of no financial loss (OR, 3.85; 95% CI, 1.14 to 12.50). The model was excellent (area under the receiver operating characteristic curve, 89.6%). We conclude that low job satisfaction is a major predictor of delayed return to work.

Detection of phytoplasma by polymerase chain reaction of insect feeding medium and its use in determining vectoring ability.

A polymerase chain reaction (PCR)-based method was developed for the detection of phytoplasma in insect feeding medium (sucrose). A correlation was established between the transmissibility of Flavescence dorée phytoplasma in the experimental leafhopper vector Euscelidius variegatus and its detection by PCR in the insect feeding medium. However, phytoplasma were detected in the insects' bodies 3 weeks before they began to transmit. Hence, PCR assays of the sucrose medium reflected phytoplasma vectoring ability probably by detecting it in the insect saliva, whereas detection of phytoplasma in the insect's body did not identify it as a vector. The assay was applied to two field-collected leafhoppers suspected of being phytoplasma vectors in Israel (Orosius albicinctus and Anaceratagallia laevis). The presence of phytoplasma in the body of specimens of the latter species was assayed by PCR in 1999. Phytoplasmas were detected in insects' bodies throughout the year, with no specific seasonal pattern. In the saliva, however, no phytoplasma could be detected in the autumn. This seasonal pattern supported the validity of the feeding-medium tests and their correlation to the insect's ability to transmit phytoplasma. Transmission assays indicated, to our knowledge for the first time, that O. albicinctus and A. laevis are vectors of phytoplasma in Israel. A simple PCR-based assay is thus provided, circumventing the need for tedious biological assays and enabling epidemiological studies of phytoplasma transmissibility on a large scale.

Serum total cholesterol and cardiovascular mortality in Israeli males: the CORDIS Study. Cardiovascular Occupational Risk Factor Determination in Israeli Industry.

BACKGROUND: The degree to which serum total cholesterol predicts cardiovascular disease is uncertain. While most authors have placed TC among the most powerful risk indicators of CVD, some have claimed that it predicted CVD in women only, or even not at all. OBJECTIVE: To determine the predictive value of serum total cholesterol relative to diabetes, smoking, systolic blood pressure and body mass index (kg/m2), for cardiovascular disease mortality in 3,461 occupationally active Israeli males. METHODS: A prospective follow-up was carried out for the years 1987-1998 to determine the effect of age, smoking habits, a history of diabetes, SBP, BMI and TC, at entry, on CVD mortality. RESULTS: There were 84 CVD deaths during a total of 37,174 person-years follow up. The hazard ratios (95% confidence intervals) for CVD mortality with respect to variables at entry were: diabetes 5.2 (2.1-13.2), age 2.2 (1.7-2.9), smoking 1.3 (1.0-1.8), SBP 1.4 (1.1-2.0), TC 1.5 (1.0-2.1) and BMI 1.2 (0.7-2.2). Among non-obese, non-diabetic, normotensive subjects the hazard ratio of TC adjusted for age and smoking was 1.16 (1.09-1.22) per 10 mg/dl. In the remaining subjects it was 1.04 (0.98-1.12) only. There was a significant interaction between TC and diabetes, hypertension or obesity (P = 0.003). CONCLUSIONS: In this population of Israeli males we found an interaction between TC and other risk indicators for CVD. Confirmation is required for the unexpected finding that the predictive value of TC for CVD mortality among non-diabetic, non-obese and normotensive subjects exceeded that among subjects with either of these risk factors.