Τετάρτη, 18 Ιανουαρίου 2017

Examining the link between nonmedical use of sedatives, tranquilizers, and pain relievers with dispositions toward impulsivity among college students


Publication date: June 2017
Source:Addictive Behaviors, Volume 69
Author(s): Brittany E. Blanchard, Angela K. Stevens, Andrew K. Littlefield, Amelia E. Talley, Jennifer L. Brown
BackgroundThe association between impulsive dispositions and the use of the central nervous system (CNS) depressant alcohol has been examined extensively; however, the links between other depressant use (sedatives, tranquilizers, and pain relievers) and impulsivity have been less studied, and findings have been equivocal. This may be due, in part, to varying operationalizations of “impulsivity,” as well as issues related to the lumping versus splitting of various depressant substances when assessing use. The effect of gender on the impulsivity-depressant use relation has also yielded mixed results and remains understudied. The current study sought to determine whether lumping versus splitting of depressant substances and distinct impulsivity-related dispositions, as well as participant gender, impact the depressant-impulsivity relation.MethodParticipants were 778 undergraduate students (72% female, 80% White, 23% Hispanic), who completed a battery of self-report assessments online, including the UPPS-P.ResultsHierarchical linear models indicated that specific impulsive dispositions differentiated between users and non-users of specific depressant substances, and these relations varied by gender. For example, sensation seeking significantly differentiated between users and non-users of pain relievers for females only, whereas sensation seeking differentiated between users and non-users of tranquilizers among males but not females.ConclusionsIn addition to informing substance use research practices by providing evidence that lumping of depressant substances leads to loss of vital information, as well as demonstrating nuanced gender differences, findings can also inform screening and personality-targeted treatment practices.

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IJMS, Vol. 18, Pages 193: Anti-NMDA Receptor Encephalitis and Vaccination

Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.

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IJMS, Vol. 18, Pages 117: Ketamine Analog Methoxetamine Induced Inflammation and Dysfunction of Bladder in Rats

The novel synthetic psychoactive ketamine analog methoxetamine is reportedly being used for recreational purposes. As ketamine use can result in urinary dysfunction, we conducted the present study to investigate how methoxetamine affects the bladder. A cystometry investigation showed that female Sprague-Dawley rats experienced increased micturition frequency bladder dysfunction after receiving a daily intraperitoneal injection of 30 mg/kg methoxetamine or ketamine for periods of 4 or 12 weeks. Histologic examinations of rat bladder tissue revealed damaged urothelium barriers, as well as evidence of inflammatory cell infiltration and matrix deposition. The drug-treated rats showed significantly upregulated levels of pro-inflammatory cytokines such as IL-1β, IL-6, CCL-2, CXCL-1, CXCL-10, NGF, and COX-2. In addition, interstitial fibrosis was confirmed by increased levels of collagen I, collagen III, fibronectin and TGF-β. Besides direct toxic effect on human urothelial cells, methoxetaminealso induced the upregulation related cytokines. Our results indicate that long term methoxetamine treatment can induce bladder dysfunction and inflammation in rats. Methoxetamine was confirmed to produce direct toxic and pro-inflammatory effects on human urothelial cells. Methoxetamine-associated bladder impairment may be similar to ketamine-induced cystitis.

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IJMS, Vol. 18, Pages 137: A Thoroughly Validated Virtual Screening Strategy for Discovery of Novel HDAC3 Inhibitors

Histone deacetylase 3 (HDAC3) has been recently identified as a potential target for the treatment of cancer and other diseases, such as chronic inflammation, neurodegenerative diseases, and diabetes. Virtual screening (VS) is currently a routine technique for hit identification, but its success depends on rational development of VS strategies. To facilitate this process, we applied our previously released benchmarking dataset, i.e., MUBD-HDAC3 to the evaluation of structure-based VS (SBVS) and ligand-based VS (LBVS) combinatorial approaches. We have identified FRED (Chemgauss4) docking against a structural model of HDAC3, i.e., SAHA-3 generated by a computationally inexpensive “flexible docking”, as the best SBVS approach and a common feature pharmacophore model, i.e., Hypo1 generated by Catalyst/HipHop as the optimal model for LBVS. We then developed a pipeline that was composed of Hypo1, FRED (Chemgauss4), and SAHA-3 sequentially, and demonstrated that it was superior to other combinations in terms of ligand enrichment. In summary, we present the first highly-validated, rationally-designed VS strategy specific to HDAC3 inhibitor discovery. The constructed pipeline is publicly accessible for the scientific community to identify novel HDAC3 inhibitors in a time-efficient and cost-effective way.

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Perioperatives Atemwegsmanagement in der Mund-Kiefer-Gesichts-Chirurgie


Das Atemwegsmanagement bei mund-, kiefer- und gesichtschirurgischen Eingriffen in Allgemeinanästhesie stellt eine besondere Herausforderung dar. Die anatomischen Atemwegsstrukturen können sowohl durch angeborene als auch durch erworbene Pathologien verändert sein, sodass nach sorgfältiger Evaluation durch einen Anästhesisten die sicherste Strategie zur Atemwegssicherung gefunden werden muss. Dies gelingt nur in eingespielter Zusammenarbeit der verschiedenen Disziplinen und unter differenzierter Verwendung unterschiedlicher Techniken. Als Standardverfahren zur Intubation des schwierigen Atemwegs gilt die fiberoptische Wachintubation des spontan atmenden Patienten. Im Falle des unerwarteten schwierigen Atemwegs kann ein erfahrener Anästhesist mit modernen Geräten, wie z. B. Videolaryngoskopen, die meisten problematischen Situationen bewältigen.

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Intelligent Monitoring? Assessing the ability of the Care Quality Commission's statistical surveillance tool to predict quality and prioritise NHS hospital inspections


The Care Quality Commission (CQC) is responsible for ensuring the quality of the health and social care delivered by more than 30 000 registered providers in England. With only limited resources for conducting on-site inspections, the CQC has used statistical surveillance tools to help it identify which providers it should prioritise for inspection. In the face of planned funding cuts, the CQC plans to put more reliance on statistical surveillance tools to assess risks to quality and prioritise inspections accordingly.


To evaluate the ability of the CQC's latest surveillance tool, Intelligent Monitoring (IM), to predict the quality of care provided by National Health Service (NHS) hospital trusts so that those at greatest risk of providing poor-quality care can be identified and targeted for inspection.


The predictive ability of the IM tool is evaluated through regression analyses and 2 testing of the relationship between the quantitative risk score generated by the IM tool and the subsequent quality rating awarded following detailed on-site inspection by large expert teams of inspectors.


First, the continuous risk scores generated by the CQC's IM statistical surveillance tool cannot predict inspection-based quality ratings of NHS hospital trusts (OR 0.38 (0.14 to 1.05) for Outstanding/Good, OR 0.94 (0.80 to –1.10) for Good/Requires improvement, and OR 0.90 (0.76 to 1.07) for Requires improvement/Inadequate). Second, the risk scores cannot be used more simply to distinguish the trusts performing poorly—those subsequently rated either ‘Requires improvement’ or ‘Inadequate’—from the trusts performing well—those subsequently rated either ‘Good’ or ‘Outstanding’ (OR 1.07 (0.91 to 1.26)). Classifying CQC's risk bandings 1-3 as high risk and 4-6 as low risk, 11 of the high risk trusts were performing well and 43 of the low risk trusts were performing poorly, resulting in an overall accuracy rate of 47.6%. Third, the risk scores cannot be used even more simply to distinguish the worst performing trusts—those subsequently rated ‘Inadequate’—from the remaining, better performing trusts (OR 1.11 (0.94 to 1.32)). Classifying CQC's risk banding 1 as high risk and 2-6 as low risk, the highest overall accuracy rate of 72.8% was achieved, but still only 6 of the 13 Inadequate trusts were correctly classified as being high risk.


Since the IM statistical surveillance tool cannot predict the outcome of NHS hospital trust inspections, it cannot be used for prioritisation. A new approach to inspection planning is therefore required.

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Premature closure? Not so fast

Dual process theory (DPT) and the intertwined concepts of heuristics and biases, popularised by Kahneman's book Thinking Fast and Slow, are widely discussed models for analysing decision-making processes inside and outside medicine.1 The basic premise of DPT is that the brain has a fast, intuitive, but occasionally error-prone system (system 1) and a slower, energy-intensive but more accurate analytical system (system 2). Inexorably tied up with the DPT model is the idea that the errors made in system 1 are a result of shortcuts (heuristics) and predispositions (biases) and the hope that if we spent more time in system 2, cognitive errors could be mitigated.

Insights from this model have driven quality improvement and medical education efforts. Learning about how our brain succeeds and fails is interesting, humbling and motivating—but is it effective? My instinct has always been that it is, but as I have tried to...

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