What is the optimal anticoagulation level with argatroban during percutaneous coronary intervention?

Argatroban is increasingly used in patients with heparin-induced thrombocytopenia. Although the recommended activated clotting time during percutaneous coronary intervention is 300-450 s, this recommendation is based on the limited data. This single-center, retrospective study evaluated the efficacy (composite of death, myocardial infarction, or urgent revascularization) and safety (evaluated by thrombolysis in myocardial infarction major bleeding) of argatroban during percutaneous coronary intervention according to activated clotting time levels. Patients were divided into three groups according to the activated clotting time achieved during the procedure (<300s, 300-450s, and >450 s). In this study, 120 consecutive patients with confirmed or suspected heparin-induced thrombocytopenia received argatroban (241 +/- 104 mug/kg bolus, followed by a 18 +/- 10 microg/kg per min infusion) during percutaneous coronary intervention. The indication for percutaneous coronary intervention was stable angina in 20% of patients, unstable angina or non-ST elevation myocardial infarction in 58%, and ST elevation myocardial infarction in 22%. An adjunctive glycoprotein IIb/IIIa inhibitor was used in 56 patients (46.7%). When divided into three groups on the basis of the activated clotting time (<300, 300-450, >450 s), no significant difference was observed between the groups in the efficacy endpoint, which occurred in 9.8% (6/61) of patients in the group with activated clotting time less than 300 s, 19.6% (9/46) of patients in the group with activated clotting time 300-450 s, and 7.7% (1/13) of patients in the group with activated clotting time more than 450 s (P = 0.58). The rate of major bleeding was higher in the group of patients with activated clotting time more than 450 s (1.6, 0, and 15.4% patients, respectively; P = 0.006). These results suggest that in patients undergoing percutaneous coronary intervention, argatroban provides adequate anticoagulation with a low bleeding rate, when activated clotting time is maintained below 450 s.     

Accelerating regional atrophy rates in the progression from normal aging to Alzheimer’s disease

We investigated progression of atrophy in vivo, in Alzheimer’s disease (AD), and mild cognitive impairment (MCI). We included 64 patients with AD, 44 with MCI and 34 controls with serial MRI examinations (interval 1.8?±?0.7 years). A nonlinear registration algorithm (fluid) was used to calculate atrophy rates in six regions: frontal, medial temporal, temporal (extramedial), parietal, occipital lobes and insular cortex. In MCI, the highest atrophy rate was observed in the medial temporal lobe, comparable with AD. AD patients showed even higher atrophy rates in the extramedial temporal lobe. Additionally, atrophy rates in frontal, parietal and occipital lobes were increased. Cox proportional hazard models showed that all regional atrophy rates predicted conversion to AD. Hazard ratios varied between 2.6 (95% confidence interval (CI) = 1.1–6.2) for occipital atrophy and 15.8 (95% CI?=?3.5–71.8) for medial temporal lobe atrophy. In conclusion, atrophy spreads through the brain with development of AD. MCI is marked by temporal lobe atrophy. In AD, atrophy rate in the extramedial temporal lobe was even higher. Moreover, atrophy rates also accelerated in parietal, frontal, insular and occipital lobes. Finally, in nondemented elderly, medial temporal lobe atrophy was most predictive of progression to AD, demonstrating the involvement of this region in the development of AD.     

In Vitro Comparison of Rosamicin and Erythromycin Against Urinary Tract Pathogens

The in vitro activity of rosamicin and erythromycin was compared at various pH values against 311 strains of bacteria representing common urinary tract pathogens. Alkalinization of the media consistently and significantly increased the antibacterial activity of rosamicin against all of the organisms tested. This was also true for erythromycin except when tested against strains of Proteus. At pH 8, rosamicin was two- to sixfold more active than erythromycin against Enterobacteriaceae. The activity of both antibiotics against Pseudomonas aeruginosa was very similar when tested at pH 8. Erythromycin was twice as active as rosamicin at pH 8 against group D streptococci. The activity of both antibiotics was bacteriostatic and inoculum size dependent, regardless of the organism tested or the pH of the test media. The greater activity of rosamicin against Enterobacteriaceae warrants clinical investigation.     

FE200041 (D-Phe-D-Phe-D-Nle-D-Arg-NH2): A peripheral efficacious kappa opioid agonist with unprecedented selectivity

The side effects typically associated with the clinical profiles of opioid mu-receptor agonists have driven continuing efforts to identify novel efficacious analgesics, including agonists acting at opioid kappa receptors. Unfortunately, the therapeutic potential of kappa agonists seems limited by significant central nervous system side effects. Kappa opioid agonists, however, exhibit potent peripherally mediated antihyperalgesic and antinociceptive effects, suggesting that a peripherally acting kappa agonist may be efficacious in pain control with a more desirable safety profile than that associated with currently available opioids. Here, we report an all D-amino acid tetrapeptide characterized as a novel, highly selective kappa opioid receptor agonist. FE200041 (D-Phe-D-Phe-D-Nle-D-Arg-NH2) showed selectivity for the human kappa opioid receptor of greater than 30,000- and 68,000-fold versus human mu opioid receptor and human delta-opioid receptor receptors, respectively, and efficacious agonist activity using in vitro tissue assays. FE200041 produced local, peripheral antinociception in the hindpaw ipsilateral, but not contralateral, to injection. Antinociceptive effects of FE200041 in the mouse acetic acid writhing assay lasted over 60 min and were antagonized by naloxone and by selective kappa, but not mu, opioid receptor antagonists. FE200041 significantly inhibited acetic acid writhing and inhibited formalin-induced flinching in rats. FE200041 did not elicit sedation or motor impairment after systemic administration at a dose 10-fold higher than that needed to achieve antinociception. FE200041 is thus a potent peripherally restricted opioid kappa agonist with no demonstrable side effects typical of kappa agonists with central nervous system activity and with unprecedented selectivity for the opioid kappa receptor. The pharmacology of this compound suggests the possibility of therapeutic application.     

Interaction Behaviors of Bilingual Parents With Their Young Children With Autism Spectrum Disorder

Given concerns that bilingual exposure might confuse children with disabilities—including autism spectrum disorder (ASD)—bilingual parents may restrict exposure to one language, often the community-dominant language. We investigated a potential consequence of this decision; the possibility that non-native language use might influence parental communicative behaviors during interaction with the child. We recruited 39 parent–child dyads, each with a young child with ASD (mostly boys) and parent/carer (mostly mothers). Parents were either monolingual speakers of community-dominant English (n = 20) or bilingual with English as the second language (n = 19). We confirmed our assumption that the latter group would have significantly poorer non-native English language via standardized assessment of expressive vocabulary, and ensured children were matched on age, ASD symptoms, and developmental level. We sampled parent–child interaction—including in each of bilinguals’ native and non-native languages—and coded parents’ amount and complexity of speech, communicative synchrony, and imitations and expansions of their child’s speech. Few differences presented across bilingual parents’ native versus non-native language samples, but this group showed reduced synchrony and use of expansions compared to monolinguals. Further, bilinguals’ English-language knowledge was associated with self-reported comfort using this language and with two coded interaction measures. These empirical data only partially support qualitative accounts that non-native language use may influence bilingual parents’ interaction behaviors with their young children. With growing rates of ASD diagnosis and increasing cultural/linguistic diversity around the world, further dedicated clinical and experimental attention to this issue is clearly warranted.     

The Portrayal of Gambling and Cognitive Biases in Chinese Gambling-Themed Movies

This study was undertaken to explore movie portrayals of Chinese gambling behaviors. More than 350 observation hours were spent reviewing and documenting 39 Chinese gambling-themed movies. In general, observations found that Chinese gambling-themed movies tended to portray gambling positively. More importantly, cognitive distortions were represented commonly in these Chinese gambling-themed movies. Specifically, active illusionary control via skill efficacy was depicted most frequently, followed by cognitive control, talismanic control, and behavioral control. Passive illusionary control via luck was represented regularly in these movies. These findings will help policymakers to understand the extent and types of distortion better as well as misinformation that Chinese gambling-themed movies convey to the public.