Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

Selective Laser Melting of Al-Based Matrix Composites with Al2O3 Reinforcement: Features and Advantages

Aluminum matrix composites (AMC) are of great interest and importance as high-performance materials with enhanced mechanical properties. Al₂O₃ is a commonly used reinforcement in AMCs fabricated by means of various technological methods, including casting and sintering. Selective laser melting (SLM) is a suitable modern method of the fabrication of net-shape fully dense parts from AMC with alumina. The main results, achievements, and difficulties of SLM applied to AMCs with alumina are discussed in this review and compared with conventional methods. It was shown that the initial powder preparation, namely the particle size distribution, sphericity, and thorough mixing, affected the final microstructure and properties of SLMed materials drastically. The distribution of reinforcing particles tends to consolidate the near-melting pool-edges process because of pushing by the liquid–solid interface during the solidification process that is a common problem of various fabrication methods. The achievement of an homogeneous distribution was shown to be possible through both the thorough mixing of the initial powders and the precise optimization of SLM parameters. The strength of the AMCs fabricated by the SLM method was relatively low compared with materials produced by conventional methods, while for superior relative densities of more than 99%, hardness and tribological properties were obtained, making SLM a promising method for the Al-based matrix composites with Al₂O₃.     

Depression in a Patient With Alzheimer Disease

This is a case study of a 73-year-old woman recently diagnosed with Alzheimer disease living in an assisted living facility who presented to an outpatient behavioral health clinic with her son for evaluation and treatment of depression. This article highlights the presentation of depression (a diagnosis) versus apathy (a symptom of Alzheimer disease) and the need to assess for co-occurring mood disorders that warrant pharmacologic intervention as well as treatment for cognitive decline in Alzheimer disease.     

Burn intensive care treatment over the last 30 years: Improved survival and shift in case-mix

PurposeMortality in burn intensive care unit (ICU) has been decreasing and treatment appears to be changing. The aims of this study: (1) examine outcome in burn patients, (2) examine changes in ICU indication and (3) explore the influence of a changing case-mix.MethodsRetrospective study in patients admitted to ICU (1987–2016). Four groups were specified: major burns (≥15% TBSA), inhalation injury with small injury (<15% TBSA, inhalation injury), watchful waiting (<15% TBSA, without inhalation injury), tender loving care (patients withheld from treatment). Logistic regression was performed to evaluate the relation between case-mix and outcome.ResultsOverall mortality decreased to 7%. Mortality of major burns decreased by 15%. The major burn group decreased by 36%. The inhalation injury and watchful waiting group increased by 9% and 21%. The percentage of ventilated patients increased by 14% in the major burn group. 40% of patients were ventilated in the watchful waiting group.ConclusionsAfter correction for case-mix, survival improved, mainly in the major burn group. Case-mix shifted towards inhalation injury and watchful waiting. Growth of the watchful waiting group is not necessarily harmful. However, the increase of mechanical ventilation could be. We suggest raising awareness for risks and consequences of mechanical ventilation.     

Vitamin B6 Addiction in Acute Myeloid Leukemia

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Decoding attention control and selection in visual spatial attention

Event‐related potentials (ERPs) are used extensively to investigate the neural mechanisms of attention control and selection. The univariate ERP approach, however, has left important questions inadequately answered. We addressed two questions by applying multivariate pattern classification to multichannel ERPs in two cued visual spatial attention experiments (N = 56): (a) impact of cueing strategies (instructional vs. probabilistic) on attention control and selection and (b) neural and behavioral effects of individual differences. Following cue onset, the decoding accuracy (cue left vs. cue right) began to rise above chance level earlier and remained higher in instructional cueing (~80 ms) than in probabilistic cueing (~160 ms), suggesting that unilateral attention focus leads to earlier and more distinct formation of the attention control set. A similar temporal sequence was also found for target‐related processing (cued target vs. uncued target), suggesting earlier and stronger attention selection under instructional cueing. Across the two experiments: (a) individuals with higher cue‐related decoding accuracy showed higher magnitude of attentional modulation of target‐evoked N1 amplitude, suggesting that better formation of anticipatory attentional state leads to stronger modulation of target processing, and (b) individuals with higher target‐related decoding accuracy showed faster reaction times (or larger cueing effects), suggesting that stronger selection of task‐relevant information leads to better behavioral performance. Taken together, multichannel ERPs combined with machine learning decoding yields new insights into attention control and selection that complement the univariate ERP approach, and along with the univariate ERP approach, provides a more comprehensive methodology to the study of visual spatial attention.