Control of glycolytic dynamics by hexose transport in Saccharomyces cerevisiae

AbstractIt is becoming accepted that steady-state fluxes are not necessarily controlled by single rate-limiting steps. This leaves open the issue whether cellular dynamics are controlled by single pacemaker enzymes, as has often been proposed. This paper shows that yeast sugar transport has substantial but not complete control of the frequency of glycolytic oscillations. Addition of maltose, a competitive inhibitor of glucose transport, reduced both average glucose consumption flux and frequency of glycolytic oscillations. Assuming a single kinetic component and a symmetrical carrier, a frequency control coefficient of between 0.4 and 0.6 and an average-flux control coefficient of between 0.6 and 0.9 were calculated for hexose transport activity. In a second approach, mannose was used as the carbon and free-energy source, and the dependencies on the extracellular mannose concentration of the transport activity, of the frequency of oscillations, and of the average flux were compared. In this case the frequency control coefficient and the average-flux control coefficient of hexose transport activity amounted to 0.7 and 0.9, respectively. From these results, we conclude that 1) transport is highly important for the dynamics of glycolysis, 2) most but not all control resides in glucose transport, and 3) there should at least be one step other than transport with substantial control

Treating Spinal Pain

markdownabstractThis thesis covers: (1) the Dutch physiotherapist guideline for diagnosing and treating spinal pain. (2) The PRINS-study; Prevalence of RIsk groups in Neck and back pain patients according to the STarT back screening tool. This is a prospective cohort study including 284 patients whose primary complaint was low back pain or neck pain that consulted the physiotherapist or general practitioner. (3) The secondary analysis of the PACE-trial data concerning 1642 patients studying the efficacy of paracetamol taken regularly or as-needed compared with placebo to improve time to recovery from acute low back pain. We analyzed and described the magnitude of patient reported non-adherence with guideline-recommended care for acute low back pain, and to explore possible factors associated with non-adherence

The Effect of a New Payment System on Physiotherapeutic Management of Patients With Low Back Pain in Primary Care

OBJECTIVE: To evaluate differences regarding the number of treatment sessions, costs, and outcomes (including relapses) between a regular payment-per-session system and the recently introduced product payment system. DESIGN: Prospective cohort study. SETTING: Dutch physical therapy practices in primary care over a 2-year period. PARTICIPANTS: 16,103 patients with low back pain (LBP). INTERVENTION: The new product payment system is compared with the regular payment-per-session system. MAIN OUTCOME MEASURES: Pain, disability, recovery, number of physical therapy sessions, therapy duration, costs (per episode), and LBP relapse. RESULTS: At baseline, we found greater pain and disability scores associated with an increased risk profile in both payment systems. With regard to the payment systems, we found greater costs (€283.8 vs €210.8) and a greater percentage of relapse (4.5% vs 2.8%) for the product payment system compared with the payment-per-session system. Comparing the 2 payment systems within each risk strata, we found no significant differences, except for a decrease in pain in the medium-risk stratum. Concerning the therapy characteristics, we found that in the payment-per-session group, the therapy took 6 days longer for low-risk patients (median 27 vs 21 days) and 7 days shorter for high-risk patients (median 42 vs 49 days) compared with the product payment group. Moreover, the mean number of sessions in the payment-per-session group was greater for low-risk patients (5.4 vs 4.8 sessions) and lower for high-risk patients (7.7 vs 8.1 sessions) compared with the payment-per-session group. Finally, the costs were significantly greater in all strata of the product payment group compared with the payment-per-session group. CONCLUSIONS: The 2 payment systems are largely comparable regarding patient outcomes, therapy duration, and treatment sessions. Both the average cost per patient per LBP episode and the number of relapses in the product payment system are statistically significantly greater than in the payment-per-session system

Reliability, Measurement Error, Responsiveness, and Minimal Important Change of the Patient-Specific Functional Scale 2.0 for Patients With Nonspecific Neck Pain

OBJECTIVE: The Patient-Specific Functional Scale (PSFS) is a patient-reported outcome measure used to assess functional limitations. Recently, the PSFS 2.0 was proposed; this instrument includes an inverse numeric rating scale and an additional list of activities that patients can choose. The aim of this study was to assess the test-retest reliability, measurement error, responsiveness, and minimal important change of the PSFS 2.0 when used by patients with nonspecific neck pain. METHODS: Patients with nonspecific neck pain completed a numeric rating scale, the PSFS 2.0, and the Neck Disability Index at baseline and again after 12 weeks. The Global Perceived Effect (GPE) was also collected at 12 weeks and used as an anchor. Test-retest measurement was assessed by completion of a second PSFS 2.0 after 1 week. Measurement error was calculated using a Bland-Altman plot. The receiver operating characteristic method with the anchor (GPE) functions as the reference standard was used for calculating the minimal important change. RESULTS: One hundred patients were included, with 5 lost at follow-up. No floor and ceiling effects were reported. In the test-retest analysis, the mean difference was 0.15 (4.70 at first test and 4.50 at second test). The ICC (mixed models) was 0.95, indicating high agreement (95% CI = 0.92-0.97). For measurement error, the upper and lower limits of agreement were 0.95 and -1.25 points, respectively, with a smallest detectable change of 1.10. The minimal important change was determined to be 2.67 points. The PSFS 2.0 showed satisfactory responsiveness, with an area under the curve of 0.82 (95% CI = 0.70-0.93). There were substantial to high correlations between the change scores of the PSFS 2.0 and the Neck Disability Index and GPE (0.60 and 0.52, respectively; P &lt; .001). CONCLUSION: The PSFS 2.0 is a reliable and responsive patient-reported outcome measure for use by patients with neck pain.</p

Clinical validation of grouping conservative treatments in neck pain for use in a network meta-analysis:a Delphi consensus study

Background: A network meta-analysis aims to help clinicians make clinical decisions on the most effective treatment for a certain condition. Neck pain is multifactorial, with various classification systems and treatment options. Classifying patients and grouping interventions in clinically relevant treatment nodes for a NMA is essential, but this process is poorly defined. Objective: Our aim is to obtain consensus among experts on neck pain classifications and the grouping of interventions into nodes for a future network meta-analysis. Design: A Delphi consensus study involving neck pain experts worldwide. Methods:We invited authors of neck pain clinical practice guidelines published from 2014 onwards. The Delphi baseline questionnaire was developed based on the findings of a scoping review, including four items on classifications and 19 nodes. Participants were asked to record their level of agreement on a seven-point Likert scale or using Yes/No/Not sure answer options for the various statements. We used descriptive analysis to summarise the responses on each statement with content analysis of the free-text comments. Results: In total, 18/80 experts (22.5%) agreed to participate in one or more Delphi rounds. We needed three rounds to reach consensus for two classification of neck pain: one based on aetiology and one on duration. In addition, we also reached consensus on the grouping of interventions, including a definition of each node, with the number of nodes reduced to 17. Conclusion: With this consensus we clinically validated two neck pain classifications and grouped conservative treatments into 17 well-defined and clinically relevant nodes.</p