Transcriptional Modulation of the Hippo Signaling Pathway by Drugs Used to Treat Bipolar Disorder and Schizophrenia

Recent reports suggest a link between positive regulation of the Hippo pathway with bipolar disorder (BD), and the Hippo pathway is known to interact with multiple other signaling pathways previously associated with BD and other psychiatric disorders. In this study, neuronal-like NT2 cells were treated with amisulpride (10 µM), aripiprazole (0.1 µM), clozapine (10 µM), lamotrigine (50 µM), lithium (2.5 mM), quetiapine (50 µM), risperidone (0.1 µM), valproate (0.5 mM), or vehicle control for 24 h. Genome-wide mRNA expression was quantified and analyzed using gene set enrichment analysis (GSEA), with genes belonging to Hippo, Wnt, Notch, TGF- β, and Hedgehog retrieved from the KEGG database. Five of the eight drugs downregulated the genes of the Hippo pathway and modulated several genes involved in the interacting pathways. We speculate that the regulation of these genes, especially by aripiprazole, clozapine, and quetiapine, results in a reduction of MAPK and NFκB pro-inflammatory signaling through modulation of Hippo, Wnt, and TGF-β pathways. We also employed connectivity map analysis to identify compounds that act on these pathways in a similar manner to the known psychiatric drugs. Thirty-six compounds were identified. The presence of antidepressants and antipsychotics validates our approach and reveals possible new targets for drug repurposing.     

Growth and characterization of epitaxial SrBi2Ta2O9 films on (110) SrTiO3 substrates

Abstract

SrBi₂Ta₂O₉ (SBT) is an attractive material for nonvolatile ferroelectric memory applications. In this paper we report on the deposition of highly epitaxial and smooth SrBi₂Ta₂O₉ films on (110) SrTiO₃substrates. The films were grown by pulsed laser deposition at temperatures ranging from 600 to 800°C and at various laser fluences from a Bi-excess SBT target. The background oxygen pressure was maintained at 28 Pa during the film deposition. Structural characterization of the films was performed by x-ray diffraction. Atomic force microscopy was used to investigate morphology and growth of the films. The films grew with preferred (115) or (116) orientation. The roughness was of the order of unit cell height. The films display a growth pattern resulting in corrugated film morphology.     

The functions of aggression by male teenagers.

A selectionist theory states that violence by males toward male peers originally served specific functions and violence to female peers served others. Differences in self-reported victimization and perpetration in studies of 1,452 high school students were hypothesized. In Study 1, male-to-male aggression was reported to be more prevalent than male-to-female aggression. For male-to-male aggression, perpetrator reports agreed with or exceeded victim reports, and victims were more often strangers than close friends. In contrast, for male-to-female aggression, there were consistently fewer reports from perpetrators than from victims, and victims were less often strangers than girlfriends. Study 2 obtained similar findings for reported frequency, number of victims and perpetrators, and sexual aggression. Study 3 showed that girls' aggression contrasted with that by boys with respect to intra- versus intersex aggression and perpetrator–victim agreement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tasting spoons: Assessing how the material of a spoon affects the taste of the food

This study investigated the effect that the taste of certain metals has on the perception of food. Four spoons plated with different metals (gold, copper, zinc, and stainless steel) were used to taste cream samples having different tastes: sweet, sour, bitter, salty, and plain. The results revealed that the zinc and copper spoons, in addition to transferring a somewhat metallic and bitter taste, enhanced to a greater or lesser extent, each cream’s dominant taste. Contrary to our expectations, the metallic taste of the copper and zinc spoons did not seem to affect the pleasantness of the samples significantly. These findings reveal that the effect that the metals from which cutlery can be made have on food perception differs from that found when the metal salts are added to the composition of the food itself.     

Lipidomic Approaches to Study HDL Metabolism in Patients with Central Obesity Diagnosed with Metabolic Syndrome

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors characterised by central obesity, atherogenic dyslipidaemia, and changes in the circulating lipidome; the underlying mechanisms that lead to this lipid remodelling have only been partially elucidated. This study used an integrated “omics” approach (untargeted whole serum lipidomics, targeted proteomics, and lipoprotein lipidomics) to study lipoprotein remodelling and HDL composition in subjects with central obesity diagnosed with MetS (vs. controls). Compared with healthy subjects, MetS patients showed higher free fatty acids, diglycerides, phosphatidylcholines, and triglycerides, particularly those enriched in products of de novo lipogenesis. On the other hand, the “lysophosphatidylcholines to phosphatidylcholines” and “cholesteryl ester to free cholesterol” ratios were reduced, pointing to a lower activity of lecithin cholesterol acyltransferase (LCAT) in MetS; LCAT activity (directly measured and predicted by lipidomic ratios) was positively correlated with high-density lipoprotein cholesterol (HDL-C) and negatively correlated with body mass index (BMI) and insulin resistance. Moreover, many phosphatidylcholines and sphingomyelins were significantly lower in the HDL of MetS patients and strongly correlated with BMI and clinical metabolic parameters. These results suggest that MetS is associated with an impairment of phospholipid metabolism in HDL, partially led by LCAT, and associated with obesity and underlying insulin resistance. This study proposes a candidate strategy to use integrated “omics” approaches to gain mechanistic insights into lipoprotein remodelling, thus deepening the knowledge regarding the molecular basis of the association between MetS and atherosclerosis.     

Collection of daily patient reported outcomes is feasible and demonstrates differential patient experience in chronic kidney disease

Introduction: Patient reported outcomes (PROs) are a critical metric documenting the impact of disease and treatment from the patient's perspective. A variety of generic and disease specific PRO measures (PROMs) are used in chronic kidney disease (CKD) but studies are primarily cross‐sectional. None of the available PROMs are designed for frequent iterative application. Methods: An online PROM for daily use in dialysis and CKD 4/5 patients was developed. The custom website utilised visual analogue scales to capture 6 PROs (general well being (GWB), pain, sleep, breathing, energy, and appetite). Outcomes of interest were uptake, response rates, intermodality variation, and change in PRO corresponding to predefined events. Findings: Forty‐three patients submitted at least once and 34 submitted beyond 30 days. Median follow‐up was 247 days, 64% male, age 62 ± 12 years. In individuals submitting for >30 days, dialysis patients had significantly worse median scores compared to CKD for sleep (47[32–80], 97[76–99], P = 0.003), appetite (66[50–96], 97[88–100], P = 0.008), energy (47[40–89], 84[67–96], P = 0.031), and GWB (63[49–94], 93[71–98], P = 0.026). Patients demonstrated a variety of stable bandwidths of response, deviations from this were associated with specific events e.g., acute admission, vascular procedures, disturbed fluid status, and dialysis start. Discussion: We successfully introduced an online, patient acceptable, iterative PROM that discriminates symptom burden, cross‐sectionally, and longitudinally. Further work will prospectively examine the predictive power of changes in PRO and more rigorously investigate the potential use of these methods to optimise patient care.     

A Single Injection of NTG-101 Reduces the Expression of Pain-Related Neurotrophins in a Canine Model of Degenerative Disc Disease

Background: Tissue sources of pain emanating from degenerative discs remains incompletely understood. Canine intervertebral discs (IVDs) were needle puncture injured, 4-weeks later injected with either phosphate-buffered saline (PBS) or NTG-101, harvested after an additional fourteen weeks and then histologically evaluated for the expression of NGFr, BDNF, TrkB and CALCRL proteins. Quantification was performed using the HALO automated cell-counting scoring platform. Immunohistochemical analysis was also performed on human IVD tissue samples obtained from spinal surgery. Immunohistochemical analysis and quantification of neurotrophins and neuropeptides was performed using an in vivo canine model of degenerative disc disease and human degenerative disc tissue sections. Discs injected with NTG-101 showed significantly lower levels of Nerve Growth Factor receptor (NGFr/TrkA, p = 0.0001), BDNF (p = 0.009), TrkB (p = 0.002) and CALCRL (p = 0.008) relative to PBS injections. Human IVD tissue obtained from spinal surgery due to painful DDD show robust expression of NGFr, BDNF, TrkB and CALCRL proteins. A single intradiscal injection of NTG-101 significantly inhibits the expression of NGFr, BDNF, TrkB and CALCRL proteins in degenerative canine IVDs. These results strongly suggest that NTG-101 inhibits the development of neurotrophins that are strongly associated with painful degenerative disc disease and may have profound effects upon the management of patients living with discogenic pain.     

Hydrogen for heat: Using underground hydrogen storage for seasonal energy shifting in northern climates

To determine if a power-to-gas pilot-scale plant would be possible in Oregon, a feasibility study was conducted that assessed the technical, political, economic, environmental, safety, and policy aspects of a potential project in the region. The results of this study were submitted as part of Oregon State University – Cascades' entry to the Hydrogen Education Foundation's 2018 student design competition. The Pacific Northwest has a need for long term energy storage (seasonal energy shifting) due to seasonally available low-priced, low-carbon electricity. There appears to be the political motivation and the technical feasibility to install a demonstration-scale power-to-gas plant in the region to assess the technical and economic performance of the system when exposed to real-world boundary conditions. However, preliminary economic analyses show the system will be challenged by low capacity factor operation resulting in a levelized cost of hydrogen of $121.81/kg_H2 when only using otherwise curtailed electricity, or $8.84/kg_H2 when running continuously for 6 months per annum. To fund a pilot scale plant a renewable gas development surcharge of $0.18/therm is proposed as a way for willing customers to support the decarbonization mission. There is precedent within the utility for such an incentive, indicating that it would be approved by the utility commission and could be a viable path forward for a pilot-scale plant.     

Biological and environmental exposure monitoring of volatile organic compounds among nail technicians in the Greater Boston area

Nail technicians are exposed to volatile organic compounds (VOCs) from nail products, but no studies have previously measured VOC biomarkers for these workers. This study of 10 nail technicians aimed to identify VOCs in nail salons and explore relationships between air concentrations and biomarkers. Personal and area air samples were collected using thermal desorption tubes during a work shift and analyzed using gas chromatography/mass spectrometry (GC/MS) for 71 VOCs. Whole blood samples were collected pre‐shift and post‐shift, and analyzed using GC/MS for 43 VOCs. Ventilation rates were determined using continuous CO₂ measurements. Predominant air VOC levels were ethyl methacrylate (median 240 µg/m³), methyl methacrylate (median 205 µg/m³), toluene (median 100 µg/m³), and ethyl acetate (median 639 µg/m³). Blood levels were significantly higher post‐shift than pre‐shift for toluene (median pre‐shift 0.158 µg/L and post‐shift 0.360 µg/L) and ethyl acetate (median pre‐shift <0.158 µg/L and post‐shift 0.510 µg/L); methacrylates were not measured in blood because of their instability. Based on VOCs measured in these seven nail salons, we estimated that emissions from Greater Boston area nail salons may contribute to ambient VOCs. Ventilation rates did not always meet the ASHRAE guideline for nail salons. There is a need for changes in nail product formulation and better ventilation to reduce VOC occupational exposures.     

Video-assisted pulmonary resection surgery. Technique, indications and first results

Video-assisted thoracic surgery (VATS) is a compromise between conventional thoracic surgery performed via a thoracotomy of variable dimensions and surgical videothoracoscopy, which, using only small operating channels, requires the use of specific instruments, gives a field of vision exclusively by video camera and raises the delicate problem of extraction of the resection specimen. VATS is performed via a minithoracotomy, 3.5 to 5 cm long, using a video camera. In this way, the operator has two forms of vision throughout the operation: direct vision through the orifice of the minithoracotomy and visualization of the video screen. This technique also allows extraction of the resection specimen at the end of the operation. Between February and May 1993, 20 patients (14 males and 6 females with a mean age of 56 years) underwent lung resection by VATS (18 lobectomies and 2 pneumonectomies). Eighty-eight patients had a malignant tumour and 2 had a benign disease. Lymph node dissection was routinely performed in patients with a malignant lesion. The mean size of the tumours was 3.2 cm. The operative mortality was nil. The mean operating time was 154 minutes. The postoperative course was uneventful in 14 patients, but two cases of atelectasis on DO, one bronchial infection and one chylothorax, treated medically, were observed. The authors report the current criteria of their indications as the feasibility and reliability of this new technique. Results on pain and patient comfort, postoperative analgesia requirements, recovery of respiratory function and possible long-term sequelae remain to be demonstrated, which is the objective of a current prospective study.