Optimization to low temperature activity in psychrophilic enzymes

Psychrophiles, i.e., organisms thriving permanently at near-zero temperatures, synthesize cold-active enzymes to sustain their cell cycle. These enzymes are already used in many biotechnological applications requiring high activity at mild temperatures or fast heat-inactivation rate. Most psychrophilic enzymes optimize a high activity at low temperature at the expense of substrate affinity, therefore reducing the free energy barrier of the transition state. Furthermore, a weak temperature dependence of activity ensures moderate reduction of the catalytic activity in the cold. In these naturally evolved enzymes, the optimization to low temperature activity is reached via destabilization of the structures bearing the active site or by destabilization of the whole molecule. This involves a reduction in the number and strength of all types of weak interactions or the disappearance of stability factors, resulting in improved dynamics of active site residues in the cold. Considering the subtle structural adjustments required for low temperature activity, directed evolution appears to be the most suitable methodology to engineer cold activity in biological catalysts

Direct and indirect costs attributable to osteoarthritis in active subjects

OBJECTIVE: To estimate the direct and indirect costs of osteoarthritis (OA) in an active population, and to identify factors significantly influencing these expenditures. METHODS: A cohort of 3,440 subjects employed by the Liege City Council was followed prospectively for 6 months. Subjects were asked to report monthly OA related health resource utilization (contacts with health professionals, medical examinations, drug consumption, etc.) and absence from work. Health related quality of life (HRQOL) was evaluated at baseline using the Medical Outcomes Study Short-form 36 (SF-36). Logistic regression analysis identified factors associated with the probability that the individual incurred costs, and multiple regression identified factors influencing the magnitude of these costs. RESULTS: A total of 1,811 subjects filled in at least one questionnaire (response rate 52%). The mean duration of followup was 3.46 months. Self-reported prevalence of OA was 34.1%. The mean total direct costs were 44.5 euros per OA patient-month. Contacts with health professionals, medical examinations, drugs, and hospital stays accounted for 23.7 euros, 8.7 euros, 6.7 euros, and 4.9 euros, respectively, per OA patient-month. The average number of sick-leave days was 0.8 per OA patient-month. From a payer's perspective, this loss of productivity represented a mean cost of 64.5 euros per OA patient-month. We also recorded 0.02 mean days off work per active subject-month due to informal care by relatives, yielding a mean cost of 1.8 euro per active subject-month for the employer. Poorer scores for most of the dimensions of the SF-36 at baseline were significantly associated with greater likelihood of incurring direct and indirect costs and with higher costs among subjects who reported costs. If we consider the overall cohort of active subjects, the burden of OA related to the direct and indirect costs was 15.2 euros and 23.8 euros, respectively, per active subject-month. CONCLUSION: Direct and indirect costs attributable to OA are substantial, with productivity related costs being predominant. Poorer HRQOL was a major determinant of these expenditures

The direct and indirect costs of the chronic management of osteoporosis: a prospective follow-up of 3440 active subjects

Introduction: The objective of this study was to estimate the direct and indirect costs attributable to osteoporosis (OP) from a societal and a payer's perspective among active subjects living in Belgium and employed in the public workforce. Materials and methods: A cohort of 3440 subjects employed by the Liege City Council was followed for 6 months. The City Council employees were invited to fill a monthly log of the data related to their utilization of health resources ( contacts with health professionals, medical examinations, drug use,...) due to OP. Information on work disability ( number of days of sick leave) and on informal care ( number of days off work incurred by active subjects in helping relatives or friends suffering from OP) was also collected. Results: Of those asked to participate in the study, 1,811 subjects filled in at least one questionnaire. The mean duration of follow-up was 3.46 months. Self-reported prevalence of OP at inclusion was 5.3%. OP subjects were significantly older (52.7 +/- 6.1 years) than normal subjects (45.5 +/- 9.8 years) ( p< 0.05) and included more women (85.3 vs. 55.9%). Direct costs came to E44.6 per OP patient-month: E10.9 was spent on contact with health professionals, E19.0 on medical examinations, E12.1 on drugs and E2.6 on hospitalizations. During this 6-month study, a total of 140 days of sick leave was recorded ( mean: 0.4 per OP patient-month). From a payer's perspective, this loss in productivity yielded a mean cost of E34.05 per OP patient-month. A mean number of days off work of 0.018 per active subject-month, attributable to informal care, was recorded. These days of inactivity represented, for the employer, a mean cost of E1.8 per active subject-month. Conclusion: The results of this survey of a large sample of active subjects confirm that OP-related expenditures, both for medical care and for loss of productivity, are significant