Chemo-Sensitive Running Droplet

Chemical control of the spontaneous motion of a reactive oil droplet moving on a glass substrate under an aqueous phase is reported. Experimental results show that the self-motion of an oil droplet is confined on an acid-treated glass surface. The transient behavior of oil-droplet motion is also observed with a high-speed video camera. A mathematical model that incorporates the effect of the glass surface charge is built based on the experimental observation of oil-droplet motion. A numerical simulation of this mathematical model reproduced the essential features concerning confinement within a certain chemical territory of oil-droplet motion, and also its transient behavior. Our results may shed light on physical aspects of reactive spreading and a chemotaxis in living things.Comment: 17 pages, 10 figure

静注塩酸リドカインの鎮痛作用の機序 : 脊髄後角ニューロン活動の抑制

To elucidate the mechanisms of analgesic action of intraveously administered local anesthetics, effects of lidocaine hydrochloride on dorsal-horn nociceptive neurons were studied in spinal cord transected, decerebratecl cats utilizing extracellular microelectrode recording techniques. All single units studied (n=37) responded to high threshold mechanical as well as noxious heat stimuli (radiant heat : using Hardy-Wollf-Goodell Dolorimeter). The mean spontaneous discharge frequency of the neurons studied was 9.5 ± 1.0 (mean ± 1. S.E.) I.P.S. (impulse per second). When radient heat stimuli (skin temp. 49 ℃) were given, the mean value of the average discharge frequency increased to 33.9 ± 2.5 I.P.S.. Lidocaine 2.5, 5.0, and 10.0 mg/kg i. v. produced dose related suppression of both spontaneous activities and responses to noxious heat stimulation. By above doses of lidocaine, the maximum suppression of the pontaneous activities observed at 3 to 7 min after lidocaine i. v. were 37, 68 and 75 percent, respectively; those of heat evoked response were 17, 48 and 61 percent, respectively (p<0.05). The threshold skin temperature to noxious heat stimuli increased from 44.7 ± 0.4 ℃ (during control) to 46.3 ± 0.7 ℃ with lidocaine 5.0 mg/kg (p<0.05), to 47.8 ± 0,8 ℃ with lidocaine 10.0 mg/kg (p<0.01). Lidocaine also suppressed responses to non-noxious mechanical stimuli (jet air) of the same neurons. It is suggested that lidocaine may block conduction of nociceptive impulses, at least in part, by suppression of spinal-cord nociceptive neurons

Association Between Chronic Hepatitis C Virus Infection and Myocardial Infarction Among People Living With HIV in the United States.

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR)&nbsp;=&nbsp;1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR&nbsp;=&nbsp;0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR&nbsp;=&nbsp;2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research

麻薬性鎮痛薬の脊髄レベルにおける鎮痛機序 : その1 オピエイトレセプターサブタイプの面からの検討

This study was undertaken to examine the antinociceptive role of mu, delta and kappa opiate receptor subtypes which could be involved in spinal morphine suppression of noxiously evoked activity of spinal wide dynamic range (WDR) neurons. We extracellularly recorded the activity of a single WDR neuron evoked by noxious radiant heat (51℃) in decerebrate, spinally transected cats. In the first study, spinally administered morphine (n=22), DAGO (selective mu agonist, n=28), DADL (delta/mu agonist, n=17) and DPDPE (selective delta agonist, n=25), but not U-50,488H (selective kappa agonist, n=11), produced a significant suppression of the evoked activity in time and dose-dependent manners. In addition, intravenous naloxone (non-selective opiate antagonist) reversed the suppressive effects of all opiates studied. Intravenous ICI174,864 (selective delta antagonist) reversed the effect of DPDPE. The purpose of the second study was to evaluate the relative role of mu and delta opiate receptors in morphine suppression of noxiously evoked activity. Pretreatment with spinal β-FNA (selective mu antagonist) antagonized the suppressive effects of spinal DAGO, but not that of DPDPE. Following β-FNA pretreatment, the suppression of morphine (200 or 400 μg) was partially antagonized, however, when ICI174,864 was co-administered with morphine in β-FNA pretreated animals, there was even greater antagonism of the neuronal suppression by morphine at these dosages. In the third study, we investigated the interaction between mu and delta receptors at the spinal level. Ineffective and effective dosage of DAGO (1 or 1.5 μg, respectively) were combined with an ineffective dosage of DPDPE (30 μg). The spinal combination of DAGO and DPDPE produced synergistic suppressive effects. These results indicate that both mu and delta opiate receptors can modulate the input of somatic nociceptive information in the spinal dorsal horn and that morphine is capable of suppressing the evoked activity of WDR neurons as a result of interaction with delta receptors in addition to mu ?receptors at the spinal level. Furthermore, the synergism of mu and delta agonist suggests that the antinociceptive effects of morphine, which possess both mu and delta receptor agonists, could be a result of this synergism due to activation of both mu and delta receptors

Sensitivity analyses for misclassification of cause of death in the parametric G-formula

Cause-specific mortality is an important outcome in studies of interventions to improve survival, yet causes of death can be misclassified. Here, we present an approach to performing sensitivity analyses formisclassification of cause of death in the parametric g-formula. The g-formula is a useful method to estimate effects of interventions in epidemiologic research because it appropriately accounts for time-varying confounding affected by prior treatment and can estimate risk under dynamic treatment plans.We illustrate our approach using an example comparing acquired immune deficiency syndrome (AIDS)-related mortality under immediate and delayed treatment strategies in a cohort of therapy-naive adults entering care for human immunodeficiency virus infection in the United States. In the standard g-formula approach, 10-year risk of AIDSrelatedmortality under delayed treatment was 1.73 (95% CI: 1.17, 2.54) times the risk under immediate treatment. In a sensitivity analysis assuming that AIDS-related death was measured with sensitivity of 95% and specificity of 90%, the 10-year risk ratio comparing AIDS-related mortality between treatment plans was 1.89 (95% CI: 1.13, 3.14). When sensitivity and specificity are unknown, this approach can be used to estimate the effects of dynamic treatment plans under a range of plausible values of sensitivity and specificity of the recorded event type

Sensitivity analyses for effect modifiers not observed in the target population when generalizing treatment effects from a randomized controlled trial: Assumptions, models, effect scales, data scenarios, and implementation details

Background inform policy and practice for broad populations. The average treatment effect (ATE) for a target population, however, may be different from the ATE observed in a trial if there are effect modifiers whose distribution in the target population is different that from that in the trial. Methods exist to use trial data to estimate the target population ATE, provided the distributions of treatment effect modifiers are observed in both the trial and target population—an assumption that may not hold in practice. Methods The proposed sensitivity analyses address the situation where a treatment effect modifier is observed in the trial but not the target population. These methods are based on an outcome model or the combination of such a model and weighting adjustment for observed differences between the trial sample and target population. They accommodate several types of outcome models: linear models (including single time outcome and pre- and post-treatment outcomes) for additive effects, and models with log or logit link for multiplicative effects. We clarify the methods’ assumptions and provide detailed implementation instructions. Illustration We illustrate the methods using an example generalizing the effects of an HIV treatment regimen from a randomized trial to a relevant target population. Conclusion These methods allow researchers and decision-makers to have more appropriate confidence when drawing conclusions about target population effects

A New Lead Chemical for Strigolactone Biosynthesis Inhibitors

Several triazole-containing chemicals have previously been shown to act as efficient inhibitors of cytochrome P450 monooxygenases. To discover a strigolactone biosynthesis inhibitor, we screened a chemical library of triazole derivatives to find chemicals that induce tiller bud outgrowth of rice seedlings. We discovered a triazole-type chemical, TIS13 [2,2-dimethyl-7-phenoxy-4-(1H-1,2,4-triazol-1-yl)heptan-3-ol], which induced outgrowth of second tiller buds of wild-type seedlings, as observed for non-treated strigolactone-deficient d10 mutant seedlings. TIS13 treatment reduced strigolactone levels in both roots and root exudates in a concentration-dependent manner. Co-application of GR24, a synthetic strigolactone, with TIS13 canceled the TIS13-induced tiller bud outgrowth. Taken together, these results indicate that TIS13 inhibits strigolactone biosynthesis in rice seedlings. We propose that TIS13 is a new lead compound for the development of specific strigolactone biosynthesis inhibitors

Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis

Liver disease is a major cause of mortality among HIV-infected persons. There is limited information about the extent to which HIV disease severity impacts liver disease progression