Cooperativity of ligand binding as a function of monomer-dimer equilibrium parameters and acceptor concentration

A general monomer-dimer equilibrium system involving ligand interactions ispresented. Cooperativity features of specific limited models are analyzed by selecting the appropriate family of equilibrium constants from this general scheme. Each system is then characterized in terms of Hill coefficient dependency on alterations in values of equilibrium constants and total acceptor concentration. This method permits comparison of predicted cooperativity trends between systems. Contrasting reports concerning cooperativity dependencies for certain defined equilibrium systems are compared and the discrepancies resolved. Characteristics of cooperativity binding patterns are shown to include symmetry about dimerization association constant values, both positive and negative cooperativity for a single set of parameters, and significant changes in cooperativity features with relatively small changes in equilibrium parameters.     

Direction of Temperature Control in the Thermal Biofeedback Treatment of Vascular Headache

In order to test for the specific therapeutic effects of thermal biofeedback (TBF) for hand warming on vascular headache (HA), 70 patients with chronic vascular HA were randomly assigned to TBF for hand warming, TBF for hand cooling, TBF for stabilization of hand temperature, or biofeedback to suppress alpha in the EEG. Patients in each condition initially had high levels of expectation of therapeutic benefit and found the treatment rationales highly credible. Participants in each condition received 12 treatment sessions on a twice-per-week basis. Based on daily HA diary data gathered for 4 weeks prior to treatment and 4 weeks after treatment, HA Index was significantly (p=.003) reduced as was HA medication consumption. There were no differential reducations in HA Index or Medication Index among the four conditions. Global self-reports of improvement gathered at the end of the post-treatment monitoring period also did not differ among the four conditions. We were unable to demonstrate a specific effect of TBF for hand warming on vascular HA activity.     

Evolutionary temperature compensation of carbon fixation in marine phytoplankton

The efficiency of carbon sequestration by the biological pump could decline in the coming decades because respiration tends to increase more with temperature than photosynthesis. Despite these differences in the short‐term temperature sensitivities of photosynthesis and respiration, it remains unknown whether the long‐term impacts of global warming on metabolic rates of phytoplankton can be modulated by evolutionary adaptation. We found that respiration was consistently more temperature dependent than photosynthesis across 18 diverse marine phytoplankton, resulting in universal declines in the rate of carbon fixation with short‐term increases in temperature. Long‐term experimental evolution under high temperature reversed the short‐term stimulation of metabolic rates, resulting in increased rates of carbon fixation. Our findings suggest that thermal adaptation may therefore have an ameliorating impact on the efficiency of phytoplankton as primary mediators of the biological carbon pump.     

A gait index may underestimate changes of gait: a comparison of the Movement Deviation Profile and the Gait Deviation Index

The ability of the Movement Deviation Profile (MDP) and Gait Deviation Index (GDI) to detect gait changes was compared in a child with cerebral palsy who underwent game training. Conventional gait analysis showed that sagittal plane angles became mirrored about normality after training. Despite considerable gait changes, the GDI showed minimal change, while the MDP detected a difference equal to a shift between 10-9 on the Functional Assessment Questionnaire scale. Responses of the GDI and MDP were examined during a synthetic transition of the patient's curves from before intervention to a state mirrored about normality. The GDI showed a symmetric response on the two opposite sides of normality but the neural network based MDP gave an asymmetric response reflecting faithfully the unequal biomechanical consequences of joint angle changes. In conclusion, the MDP can detect altered gait even if the changes are missed by the GDI.     

Poor knowledge of methotrexate associated with older age and limited English-language proficiency in a diverse rheumatoid arthritis cohort

Introduction

Our objective was to determine rheumatoid arthritis (RA) patients’ understanding of methotrexate and assess whether knowledge varies by age, education, English language proficiency, or other disease-related factors.

Methods

Adults with RA (n = 135) who were enrollees of an observational cohort completed a structured telephone interview in their preferred language between August 2007 and July 2009. All subjects who reported taking methotrexate were asked 11 questions about the medication in addition to demographics, education level, and language proficiency. Primary outcome was a total score below the 50^th percentile (considered inadequate methotrexate knowledge). Bivariable and multivariable logistic regressions were performed. Covariates included demographics, language proficiency, education, and disease characteristics.

Results

Of 135 subjects, 83% were female, with a mean age of 55 ± 14 years. The majority spoke English (64%), followed by 22% Spanish and 14% Cantonese or Mandarin. Limited English language proficiency (LEP) was reported in 42%. Mean methotrexate knowledge score was 5.4 ± 2.6 (range, 0 to 10); 73 (54%) had a score lower than 5 (of 10). Age older than 55, less than high school education, LEP, better function, and biologic use were independently associated with poor knowledge.

Conclusions

In a diverse RA cohort, overall methotrexate knowledge was poor. Older age and limited proficiency in English were significant correlates of poor knowledge. Identification of language barriers and improved clinician-patient communication around methotrexate dosing and side effects may lead to improved safety and enhanced benefits of this commonly used RA medication.