Notes

High-Content Screening process with regard to Determining Nanomaterial Toxicity.
The proportion of an effective impact on drug therapy was lower in the "psychotropic drugs" group (23%) than in the "others" group (53%). CONCLUSION Drug-related safety warnings induce intended and unintended effects. The included studies are of broadly varying methodological quality. To better compare their effectiveness, studies should be conducted using standardised procedures. © 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.OBJECTIVE To assess whether baclofen-treated alcohol dependent participants show different subjective and psychophysiological responses to appetitive cues during an alcohol cue reactivity task compared to placebo, and whether these responses are associated with prospective drinking outcomes. METHODS Forty-two alcohol dependent participants (placebo n = 12, low-dose baclofen [30 mg/day] n = 18, high-dose baclofen [75 mg/day] n = 12) completed an alcohol cue reactivity task, whereby water and alcohol beverage cues were presented, with subsequent recovery periods, and subjective alcohol craving and psychophysiological indices (skin conductance; cardiovascular measures heart rate, high-frequency heart rate variability) were recorded. RESULTS High-dose baclofen-treated participants showed both overall cue reactivity to water and alcohol cues and greater recovery effects during recovery periods, revealed by high-frequency heart rate variability, when compared to low-dose- and placebo-treated participants. There were no medication effects on subjective craving. In high-dose baclofen participants only, there was a predictive effect of lower baseline heart rate variability and fewer post-test percentage of heavy drinking days. CONCLUSION There was a dose-specific rescuing effect of high-dose baclofen on the dynamic modulation of cardiovascular responses to eliciting cues. Investigation of treatment responses using psychophysiological techniques may elucidate baclofen's mechanisms of action, and identify subgroups amenable to treatment. © 2020 John Wiley & Sons Ltd.Vancomycin-resistant Enterococcus faecium (VRE) has become endemic in healthcare settings, reducing treatment options for enterococcal infections. New antimicrobials for VRE infections are a high priority, but the development of novel antibiotics is time-consuming and expensive. Essential oils (EOs) synergistically enhance the activity of some existing antibiotics, suggesting that EO-antibiotic combinations could resensitise resistant bacteria and maintain the antibiotic repertoire. The mechanism of resensitisation of bacteria to antibiotics by EOs is relatively understudied. Here, the synergistic interactions between carvacrol (1.98 mM) and cuminaldehyde (4.20 mM) were shown to reestablish susceptibility to vancomycin (0.031 mg/L) in VRE, resulting in bactericidal activity (4.73 log10 CFU/ml reduction). Gene expression profiling, coupled with β-galactosidase leakage and salt tolerance assays, suggested that cell envelope damage contributes to the synergistic bactericidal effect against VRE. The EO-vancomycin combination was also shown to kill clinical isolates of VRE (2.33-5.25 log10 CFU/ml reduction), and stable resistance did not appear to develop even after multiple passages. The in vivo efficacy of the EO-vancomycin combination was tested in a Galleria mellonella larvae assay; however, no antimicrobial action was observed, indicating that further drug development is required for the EO-vancomycin combination to be clinically useful for treatment of VRE infections. © 2020 John Wiley & Sons, Ltd.BACKGROUND Social networks and social support can influence older adults' depressive symptoms, but depressive symptoms can also influence network maintenance. This study examined longitudinal relationships between social network structure, social support, and depressive symptoms. METHODS Data are from Waves 1 (2005-2006) and 2 (2010-2011) of the National Social Life, Health, and Aging Project, a longitudinal study on health and social factors of older adults. Models examining (i) the influence of T1 network structure and T1 social support on T2 depressive symptoms; (ii) the influence of T1 depressive symptoms and T1 network structure on T2 social support; and (iii) the influence of T1 depressive symptoms and T1 social support on T2 network structure, were estimated using ordinary least squares lagged dependent variable regression models. RESULTS Evidence of reciprocal associations between social support and depressive symptoms were found, as well as social support and the number of close ties and frequency of contact. No clear reciprocal associations between social network structure and depressive symptoms were found, although density was associated with later depressive symptoms, and depressive symptoms were associated with later number of close ties. CONCLUSION The reciprocal relationship between network structure and depressive symptoms is weak, whereas social support is strongly related to both depression and network structure, suggesting the importance of having supportive ties in an older adult's personal network for positive mental health. © 2020 Japanese Psychogeriatric Society.The electronic structure of the spherical Mackay icosahedral nanosized cluster Pd 55 (P i Pr 3 ) 12 (μ 3 -CO) 20 is analyzed using DFT calculations. Results reveal that it can be considered as a regular superatom with a "magic" electron count of 20, characterized by a 1S 2 1P 6 1D 10 2S 2 configuration. Its open shell nature is associated with partial occupation of non -jellium , 4d -type, levels located on the interior of the Pd 55 kernel. This shows that the superatom model can be used to rationalise the bonding and stability of spherical ligated group-10, clusters, despite their apparent 0-electron count. © 2020 WILEY-VCH Verlag GmbH & Co. this website KGaA, Weinheim.Hepatocellular carcinoma and cholangiocarcinoma are the most common primary malignant liver tumors. Since the liver plays a key role in lipid metabolism, the study of serum phospholipid (PL) profiles may provide a better understanding of alterations in hepatic lipid metabolism. In this study, we used a high-resolution HILIC-LC-MS lipidomic approach to establish the serum phospholipidome profile of patients with liver cancer before (T0) and after tumor resection (T1) and a control group (CT) of healthy individuals. After the analysis of PL profiles, we observed that the phospholipidome of patients with liver cancer was significantly modified after the tumor resection procedure. We observed an upregulation of some phosphatidylcholine (PtdCho) species, namely, PtdCho(366), PtdCho(426), PtdCho(385), PtdCho(365), PtdCho(386) and choline plasmalogens (PlsCho), and/or 1-O-alkyl-2-acyl-glycerophosphocholine (PakCho) in patients with liver cancer at T0 compared to the CT group, and a downregulation after tumor resection (T1) when compared to T0. These results show that LC-MS can detect different serum PL profiles in patients with liver cancer, before and after tumor resection, by defining a specific PL fingerprint that was used to determine the effect of tumor and tumor resection on lipid metabolism. © 2020 AOCS.Novel psychoactive substances (NPS) are new drugs of abuse. Over the last 10 years 50-100 new NPS have been detected for the first time each year. This has led to numerous deaths and challenges to healthcare providers and law-makers worldwide. We review preclinical studies of NPS and discuss how these studies have influenced legislative decisions. We focus on the UK legal system but include experiences from Europe. We reviewed manuscripts from 2008-2019 and have summarised the in vitro and in vivo data on NPS, highlighting how these studies define pharmacological mechanisms and how they might predict harm in humans. We found that only a small percentage of NPS have been examined in preclinical studies. Most preclinical studies of NPS focus on basic pharmacological mechanisms (46% of studies reviewed) and/or addictive liability (32%) rather than toxicity and harm (24%). Very few preclinical studies into NPS include data from chronic dosing schedules (9%) or female rodents (4%). We conclude that preclinical studies can predict harm to humans, but most of the predictions are based on basic pharmacology rather than demonstrated toxicity. Some of these studies have been used to make changes to the law in the UK and Europe and perhaps, because of the paucity of toxicology data, most NPS have been placed in the highly dangerous schedule 1 or Class A category in the UK. We suggest that in silico studies and high throughput toxicology screens might be the most economical way forward to rapidly screen the health harms of NPS. © 2020 The British Pharmacological Society.Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare, severe, and recently described multisystem developmental disorder characterized by delayed psychomotor development and intellectual disability, characteristic facial features, hypotonia, poor overall growth, and visual abnormalities. Mucocutaneous manifestations have not been reported so far among individuals with ZTTK syndrome. Herein, we present a patient with ZTTK syndrome due to a de novo mutation in SON gene, who has dental abnormalities and retronychia of the toenails. We suggest that mucocutaneous features may be a part of the phenotype. © 2020 Wiley Periodicals, Inc.AIMS This investigation characterised tolerability, pharmacokinetics and pharmacodynamics of the anti-CD38 antibody TAK-079. METHODS A randomised, double-blind, placebo-controlled trial of a single intravenous (i.v.) infusion or subcutaneous (s.c.) injection of TAK-079 at escalating doses in healthy subjects (n = 74), who were followed for 92 days postexposure. RESULTS TAK-079 was well tolerated. All adverse events were mild or moderate. There were no withdrawals, infusion, or injection site reactions over the tested i.v. and s.c. doses up to 0.06 and 0.6 mg kg-1 , respectively. At higher doses, transient cytokine level increases, following i.v. administration, coincided with reduction in CD38-expressing cells; clinical symptoms included mild pyrexia, headache, and postural hypotension. Following an i.v. infusion of 0.06 mg kg-1 TAK-079, maximum observed serum concentration (Cmax ) was 100.4 (%CV 52) ng mL-1 , time to Cmax was the end of infusion and natural killer (NK_ cells were reduced 93.8 (±8.5) % from baseline levels. Following a s.c. injection of 0.6 mg kg-1 TAK-079, Cmax was 23.0 (%CV 67) ng mL-1 with time to Cmax of 24 (range 7.98-96.02) hours, and plasmablasts were subsequently reduced 93.4 (±8.8) % from predose levels. Serum immunoglobulin (Ig)M, IgA and IgG levels were reduced by 15-60% and had not returned to baseline levels within 78 days after administration at ≥0.3 mg kg-1 s.c. Reductions in NK cells at 0.6 mg kg-1 s.c. were approximately 2-3 times more durable than at 0.06 mg kg-1 i.v. CONCLUSIONS TAK-079 was well tolerated and s.c. administration elicited more durable reductions in plasmablasts and NK cells. This plasmacytolytic profile could be useful for treating disorders caused by plasma or NK cells, malignant counterparts, and/or pathogenic antibodies. © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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