Thiosquaramides: pH switchable anion transporters

The transport of anions across cellular membranes is an important biological function governed by specialised proteins. In recent years, many small molecules have emerged that mimick the anion transport behaviour of these proteins, but only a few of these synthetic molecules also display the gating/switching behaviour seen in biological systems. A small series of thiosquar-amides was synthesised and their pH-dependent chloride binding and anion transport behaviour was investigated using 1H NMR titrations, single crystal X-ray diffraction and a variety of vesicle-based techniques. Spectrophotometric titrations and DFT calculations revealed that the thiosquaramides are significantly more acidic than their oxosquaramide analogues, with pKa values between 4.0 and 9.0. This led to the observation that at pH 7.2 the anion transport ability of the thiosquaramides is fully switched OFF due to deprotonation of the receptor, but is completely switched ON at lower pH

Long-Term Effect of Participation in an Early Exercise and Education Program on Clinical Outcomes and Cost Implications, in Patients with TIA and Minor, Non-Disabling Stroke

Participation in exercise and education programs following transient ischemic attack (TIA) or minor stroke may decrease cardiovascular disease risk. The purpose of this study was to assess the long-term effect (3.5 years) of an exercise and education program administered soon after TIA or minor stroke diagnosis on clinical outcome measures (stroke classification and number, patient deaths, hospital/emergency department admission) and cost implications obtained from standard hospital records. Hospital records were screened for 60 adults (male, n = 31; 71 ± 10 years), diagnosed with TIA or non-disabling stroke, who had previously been randomised and completed either an 8-week exercise and education program, or usual care control. Follow-up clinical outcomes and cost implications were obtained 3.5 ± 0.3 years post-exercise. Participants randomised to the exercise and education program had significantly fewer recurrent stroke/TIAs (n = 3 vs. n = 13, Cohen’s d = 0.79) than the control group (P ≤ 0.003). Similar finding were reported for patient deaths (n = 0 vs. n = 4, d = 0.53), and hospital admissions (n = 48 vs. n = 102, d = 0.54), although these findings were only approaching statistical significance. The relative risk (mean; 95%CI) of death, stroke/TIAs and hospital admissions were 0.11 (0.01 to 1.98), 0.23 (0.07 to 0.72) and 0.79 (0.57 to 1.09), respectively. Hospital admission costs were significantly lower for the exercise group ($9041 ± 15,080 NZD [~$6000 ± 10,000 USD]) than the control group ($21,750 ± 22,973 NZD [~$14,000 ± 15,000 USD]) during the follow-up period (P < 0.05, d = 0.69). The present study demonstrates the long-term patient benefit and economic importance of providing secondary prevention, exercise and education programs for patients with TIA and minor stroke. URL: http://www.anzctr.org.au/; Trial Registration Number: ACTRN12611000630910