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It is obvious that people learn and that they apply what they've learned to new and varied situations. This happens so frequently, and in many cases so effortlessly, that it is easy to take the process for granted. It is not surprising, then, that so many public health interventions involve an educational component, the assumption being that once people are informed about a risk and given corrective or preventive direction, they will act appropriately. Experience has demonstrated, however, that although education may be a necessary component of behavioral change, it is not sufficient to produce it. Despite the investment of millions of dollars and decades of effort in designing information campaigns to reduce obesity, promote safe sex, eliminate cigarette smoking, and encourage annual physical examinations, a significant segment of the population continues to engage in unsafe, risky behavior. It is not until we deliberately attempt to influence specific behaviors in defined populations and contexts that we become 223

The 5.5 Mb chromosome 7q21-22 ACHE/PON1 locus harbours the ACHE gene encoding the acetylcholine hydrolyzing, organophosphate (OP)-inhibitable acetylcholinesterase protein and the paraoxonase gene PON1, yielding the OP-hydrolyzing PON1 enzyme which also displays arylesterase activity. In search of inherited and acquired ACHE-PON1 interactions we genotyped seven polymorphic sites and determined the hydrolytic activities of the corresponding plasma enzymes and of the AChE-homologous butyrylcholinesetrase (BChE) in 157 healthy Israelis. AChE, arylesterase, BChE and paraoxonase activities in plasma displayed 5.4-, 6.5-, 7.2-and 15.5-fold variability, respectively, with genotype-specific differences between carriers of distinct compound polymorphisms. AChE, BChE and arylesterase but not paraoxonase activity increased with age, depending on leucine at PON1 position 55. In contrast, carriers of PON1 M55 displayed decreased arylesterase activity independent of the ) 108 promoter polymorphism. Predicted structural consequences of the PON1 L55M substitution demonstrated spatial shifts in adjacent residues. Molecular modelling showed substrate interactions with the enzyme variants, explaining the changes in substrate specificity induced by the Q192R substitution. Intriguingly, PON1, but not BChE or arylesterase, activities displayed inverse association with AChE activity. Our findings demonstrate that polymorphism(s) in the adjacent PON1 and ACHE genes affect each other's expression, predicting for carriers of biochemically debilitating ACHE/PON1 polymorphisms adverse genome-environment interactions.

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Coronavirus disease 2019 (Covid-19) is associated with high incidence of venous and arterial thromboembolic events. Currently, there are no markers to guide antithrombotic therapy in Covid-19. Immature platelets represent a population of hyper-reactive platelets associated with arterial events. This prospective study compared consecutive Covid-19 patients (n = 47, median age = 56 years) to patients with acute myocardial infarction (AMI, n = 100, median age = 59 years) and a group of stable patients with cardiovascular risk factors (n = 64, median age = 68 years). Immature platelet fraction (IPF) and immature platelet count (IPC) were determined by the Sysmex XN-3000 auto-analyzer on admission and at subsequent time-points. IPF% on admission was higher in Covid-19 than the stable group and similar to the AMI group (4.8% [IQR 3.4-6.9], 3.5% [2.7-5.1], 4.55% [3.0-6.75], respectively, p = 0.0053). IPC on admission was also higher in Covid-19 than the stable group and similar to the

ObjectiveWe investigated the impact of clown-care on pain in 45 children with cerebral palsy who underwent recurrent Botulinum-toxin injections (age 7.04± 4.68 years). Participants were randomized to receive either clown (n = 20) or standard (n = 25) -care.MethodsPain Visual-Analogue-Scale (range 1–5) was reported before and after procedures. Pain assessment was lower for children undergoing Botulinum-toxin injections with clown-care (2.89± 1.36) compared to standard-care (3.85± 1.39; p = 0.036) even though pain anticipated prior to procedures was similar (~3).FindingsChildren who underwent the first procedure with clown-care reported lower pain even after they crossed-over to the following procedure which was standard (p = 0.048). Carryover effect was more prominent in injection-naïve children (p = 0.019) and during multiple procedures (p = 0.009). Prior pain experience correlated with pain in subsequent procedures only when first experience was standard-care (p = 0.001).ConclusionsClown-care alleviated pain sensation during Botulinum-toxin injections and initial clown-care experience reduced pain during subsequent injections even though clowns were not present.Trial registrationclinicaltrials.gov ID # NCT01377883.