Transcranial Magnetic Stimulation of the Supplementary Motor Area in the Treatment of Obsessive-Compulsive Disorder: A Multi-Site Study

Recently, strategies beyond pharmacological and psychological treatments have been developed for the management of obsessive-compulsive disorder (OCD). Specifically, repetitive transcranial magnetic stimulation (rTMS) has been employed as an adjunctive treatment in cases of treatment-refractory OCD. Here, we investigate six weeks of low frequency rTMS, applied bilaterally and simultaneously over the sensory motor area, in OCD patients in a randomized, double-blind placebo-controlled clinical trial. Twenty-two participants were randomly enrolled into the treatment (ACTIVE = 10) or placebo (SHAM = 12) groups. At each of seven visits (baseline; day 1 and weeks 2, 4, and 6 of treatment; and two and six weeks after treatment) the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was administered. At the end of the six weeks of rTMS, patients in the ACTIVE group showed a clinically significant decrease in Y-BOCS scores compared to both the baseline and the SHAM group. This effect was maintained six weeks following the end of rTMS treatment. Therefore, in this sample, rTMS appeared to significantly improve the OCD symptoms of the treated patients beyond the treatment window. More studies need to be conducted to determine the generalizability of these findings and to define the duration of rTMS’ clinical effect on the Y-BOCS. Clinical Trial Registration Number (NCT) at www.clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00616486","term_id":"NCT00616486"}}NCT00616486.     

Unravelling the Carbohydrate‐Binding Preferences of the Carbohydrate‐Binding Modules of AMP‐Activated Protein Kinase

The β subunit of adenosine monophosphate (AMP)‐activated protein kinase (AMPK), which exists as two isoforms (β1 and β2) in humans, has a carbohydrate‐binding module (CBM) that interacts with glycogen. Although the β1‐ and β2‐CBMs are structurally similar, with strictly conserved ligand‐contact residues, they show different carbohydrate affinities. β2‐CBM shows the strongest affinity for both branched and unbranched oligosaccharides and it has recently been shown that a Thr insertion into β2‐CBM (Thr101) forms a pocket to accommodate branches. This insertion does not explain why β2‐CBM binds all carbohydrates with stronger affinity. Herein, it is shown that residue 134 (Val for β2 and Thr for β1), which does not come into contact with a carbohydrate, appears to account for the affinity difference. Characterisation by NMR spectroscopy, however, suggests that mutant β2‐Thr101Δ/Val134Thr differs from that of β1‐CBM, and mutant β1‐Thr101ins/Thr134Val differs from that of β2‐CBM. Furthermore, these mutants are less stable to chemical denaturation, relative to that of wild‐type β‐CBMs, which confounds the affinity analyses. To support the importance of Thr101 and Val134, the ancestral CBM has been constructed. This CBM retains Thr101 and Val134, which suggests that the extant β1‐CBM has a modest loss of function in carbohydrate binding. Because the ancestor bound carbohydrate with equal affinity to that of β2‐CBM, it is concluded that residue 134 plays an indirect role in carbohydrate binding.     

The Effect of ultra‐high speed twin screw extrusion on ABS/organoclay nanocomposite blend properties

Acrylonitrile butadiene styrene (ABS) nanocomposites containing Cloisite 11 organoclay at 2 wt% were prepared using a 60 L/D ultra‐ high speed twin screw extruder (TSE), with speeds ranging from 400 to 4000 rpm. The purpose of this study was to investigate the effect of high shear melt processing on the intercalation and exfoliation of organoclay in the polymer, as well as the mechanical and rheological properties of the material. X‐ray Diffraction (XRD), and Transmission Electron Microscopy (TEM) results showed better intercalation of the nanofiller with increasing screw speed up to a point, and indicated an exfoliated structure of the nanocomposites extruded at 4000 rpm. Mechanical and rheological testing results indicated that by adding organoclay to ABS, the properties improved with increasing screw speed up to an optimum value of 2000 rpm. However, at the higher screw speeds of 3000 and 4000 rpm, the intense shear history led to a decrease in properties, most likely due to chain scission and molecular weight reduction. Similar trends were observed in rheological properties of the nanocomposite as well. At 2000 rpm, the results indicate that the lowering of the molecular weight due to shear effects is balanced by good intercalation/exfoliation of the organoclay. POLYM. ENG. SCI., 57:60–68, 2017. © 2016 Society of Plastics Engineers     

The origin of anomalous water diffusion in silica glasses at low temperatures

Anomalous water diffusion into SiO₂ glass was observed in a low temperature range, below ~850°C, under a constant water vapor pressure of 355 Torr (47.3 kPa). Both the effective water diffusion coefficient and water solubility exhibited an anomalous time dependence. For example, water solubility in the low temperature range increased initially, achieving much higher values than expected based on extrapolation from higher temperature data, and then decreased with time toward an equilibrium value. This phenomenon was reported earlier, but a complete explanation was not possible; a new model is presented based upon glass surface compressive stress generation and subsequent surface stress relaxation. Water diffusion can promote stress generation and stress relaxation, both of which affect the reaction between diffused molecular water and the glass structure. By considering these stress effects, the anomalous water diffusion behavior in silica glass is explained. Furthermore, the same model can account for the reversal of external tensile and compressive stress effects on water solubility and diffusivity in silica glass observed after a few hours of heat treatment at 650°C in 355 Torr water vapor pressure.     

Glass with hydration-induced compressive stress profiles

A novel potassium phospho-aluminosilicate composition is described that can be strengthened by water vapor to achieve deep compressive stress (CS) profiles. Water vapor treatment at (A) 85°C and 85% relative humidity for 40 days results in a CS of 389 ± 20 MPa and a compressive depth of layer (DOL) of 18 ± 2 μm. When treated at (B) 160°C and 0.1 MPa for 7 days, a CS of 245 ± 20 MPa and a DOL of 40 ± 2 μm is achieved. Glasses with hydration-induced stress profiles can provide high retained strength following flaw introduction compared with ion-exchanged soda-lime silicate glass. Sample treatment B also has an exemplary Vickers indentation cracking threshold value greater than 20 kgf. The hydration profile determined by secondary ion mass spectrometry (SIMS) is shown to closely match the stress profile for these samples. SIMS analysis also shows that the depth of water enrichment correlates well with the depletion depth of phosphorus. The high tendency towards water-induced strengthening for this new type of glass even enables self-strengthening by the generation of a near-surface CS profile following exposure to ambient conditions.     

Dynamic Assessment of Functional Lipidomic Analysis in Human Urine

The development of enabling mass spectrometry platforms for the quantification of diverse lipid species in human urine is of paramount importance for understanding metabolic homeostasis in normal and pathophysiological conditions. Urine represents a non‐invasive biofluid that can capture distinct differences in an individual's physiological status. However, currently there is a lack of quantitative workflows to engage in high throughput lipidomic analysis. This study describes the development of a MS/MS^ALL shotgun lipidomic workflow and a micro liquid chromatography–high resolution tandem mass spectrometry (LC–MS/MS) workflow for urine structural and mediator lipid analysis, respectively. This workflow was deployed to understand biofluid sample handling and collection, extraction efficiency, and natural human variation over time. Utilization of 0.5 mL of urine for structural lipidomic analysis resulted in reproducible quantification of more than 600 lipid molecular species from over 20 lipid classes. Analysis of 1 mL of urine routinely quantified in excess of 55 mediator lipid metabolites comprised of octadecanoids, eicosanoids, and docosanoids generated by lipoxygenase, cyclooxygenase, and cytochrome P450 activities. In summary, the high‐throughput functional lipidomics workflow described in this study demonstrates an impressive robustness and reproducibility that can be utilized for population health and precision medicine applications.     

A Novel Method for the Production of Biodiesel from the Whole Stillage-Extracted Corn Oil

The extraction of corn oil from whole stillage and condensed distillers’ solubles (CDS) with hexane and its conversion to biodiesel were investigated. The analysis of the extracted oil showed 6–8 wt.% free fatty acid (FFA) in this oil. Acid, base, acid–base, and acid–base catalyzed transesterifications with intermediate neutralization with anion exchange resin were investigated. Experiments were performed with model corn oil substrates which contained 1.0–6.0 wt.% FFA. The effect of catalyst at 0.50–1.25 wt.% was studied at a 1:8 oil/methanol molar ratio. At 6.0 wt.% FFA concentration, the acid-catalyzed scheme was slow and resulted in less than 20% yield after 4 h, while the base-catalyzed was mostly consumed by the FFA and very little conversion was achieved. The acid–base catalyzed scheme succeeded in reducing the FFA content of the oil through the acid-catalyzed stage, and yields in excess of 85% were achieved after the second stage of the reaction with a base catalyst. However, formation of water and soap prevented the separation of product phases. An alternative acid–base catalyzed scheme was examined which made use of a strong anion exchange resin to neutralize the substrate after the initial acid-catalyzed stage. This scheme resulted in the effective removal of the acid catalyst as well as the residual FFA prior to the base-catalyzed stage. The subsequent base-catalyzed stage resulted in yields in excess of 98% for a 7.0 wt.% FFA corn oil and for the corn oil extracted from CDS.