Provision of online eye movement and desensitisation therapy (EMDR) for people with post-traumatic stress disorder (PTSD): a multi-method service evaluation

Background: The evidence for the effectiveness of online EMDR for PTSD is scarce. Objective: This service evaluation aimed to assess how online EMDR compared to in-person EMDR, in terms of its potential effectiveness and acceptability to therapists and patients. Method: The evaluation was carried out in the Cardiff and Vale University Health Board Traumatic Stress Service. We compared the outcome of therapy (PTSD scores at end of treatment), number of sessions, drop-out rate, and adverse events using linear/logistic regression in those receiving online EMDR over a 12-month period with those who had received in-person therapy in the year previous to that. Interviews with therapists and clients who had provided or undertaken online EMDR explored their views and experiences of treatment. Interviews were analysed thematically. Results: 33 people received in-person EMDR (15.3 sessions, SD = 1.4), and 45 received online EMDR (12.4 sessions, SD = 0.9). 24 individuals completed therapy in-person, and 32 online. There was no evidence of a difference in therapy completion, drop-out rates or adverse events between the two delivery modes. There was weak evidence that those who completed EMDR online and had available data (N = 29), had slightly lower PTSD scores at the end of therapy compared to those who received in-person EMDR (N = 24) (17.1 (SD = 3.2) versus 24.5 (SD = 3.0), mean difference = 7.8, 95% CI −0.3, 15.9, p = .06). However, groups were not randomised and only those who completed treatment were analysed, so estimates may be biased. 11 patients and five therapists were interviewed. Overall, both therapists and clients viewed online EMDR as safe and effective. Benefits mentioned by clients included feeling more in control and not having to travel. Clients’ concerns related to lack of privacy and ‘transition time/space’ between therapy and their daily lives. Conclusion: Results suggest that online EMDR is an acceptable, safe and effective alternative to in-person EMDR for PTSD in this service. This service evaluation assessed how online Eye Movement Desensitisation and Reprocessing (EMDR) compared to in-person EMDR in people with PTSD.Individuals receiving online EMDR had lower PTSD scores at the end of therapy, but the evidence for this was weak and as this was not a randomised trial we do not know whether this was due to the mode of therapy or other characteristics of clients receiving online therapy.Clients and therapists generally viewed online EMDR as being safe and effective, and supported the availability of online EMDR for PTSD. This service evaluation assessed how online Eye Movement Desensitisation and Reprocessing (EMDR) compared to in-person EMDR in people with PTSD. Individuals receiving online EMDR had lower PTSD scores at the end of therapy, but the evidence for this was weak and as this was not a randomised trial we do not know whether this was due to the mode of therapy or other characteristics of clients receiving online therapy. Clients and therapists generally viewed online EMDR as being safe and effective, and supported the availability of online EMDR for PTSD.</p

Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?

High-throughput biology has contributed a wealth of data on chemicals, including natural products (NPs). Recently, attention was drawn to certain, predominantly synthetic, compounds that are responsible for disproportionate percentages of hits but are false actives. Spurious bioassay interference led to their designation as <u>p</u>an-<u>a</u>ssay <u>in</u>terference compound<u>s</u> (PAINS). NPs lack comparable scrutiny, which this study aims to rectify. Systematic mining of 80+ years of the phytochemistry and biology literature, using the NAPRALERT database, revealed that only 39 compounds represent the NPs most reported by occurrence, activity, and distinct activity. Over 50% are not explained by phenomena known for synthetic libraries, and all had manifold ascribed bioactivities, designating them as <u>i</u>nvalid <u>m</u>etabolic <u>p</u>anaceas (IMPs). Cumulative distributions of ∼200,000 NPs uncovered that NP research follows power-law characteristics typical for behavioral phenomena. Projection into occurrence–bioactivity–effort space produces the hyperbolic black hole of NPs, where IMPs populate the high-effort base

Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?

High-throughput biology has contributed a wealth of data on chemicals, including natural products (NPs). Recently, attention was drawn to certain, predominantly synthetic, compounds that are responsible for disproportionate percentages of hits but are false actives. Spurious bioassay interference led to their designation as <u>p</u>an-<u>a</u>ssay <u>in</u>terference compound<u>s</u> (PAINS). NPs lack comparable scrutiny, which this study aims to rectify. Systematic mining of 80+ years of the phytochemistry and biology literature, using the NAPRALERT database, revealed that only 39 compounds represent the NPs most reported by occurrence, activity, and distinct activity. Over 50% are not explained by phenomena known for synthetic libraries, and all had manifold ascribed bioactivities, designating them as <u>i</u>nvalid <u>m</u>etabolic <u>p</u>anaceas (IMPs). Cumulative distributions of ∼200,000 NPs uncovered that NP research follows power-law characteristics typical for behavioral phenomena. Projection into occurrence–bioactivity–effort space produces the hyperbolic black hole of NPs, where IMPs populate the high-effort base

The Essential Medicinal Chemistry of Curcumin

Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed

Hyphenating Centrifugal Partition Chromatography with Nuclear Magnetic Resonance through Automated Solid Phase Extraction

Centrifugal partition chromatography (CPC) and all countercurrent separation apparatus provide chemists with efficient ways to work with complex matrixes, especially in the domain of natural products. However, despite the great advances provided by these techniques, more efficient ways of analyzing the output flow would bring further enhancement. This study describe a hyphenated approach made by coupling NMR with CPC through a hybrid-indirect coupling made possible by using a solid phase extraction (SPE) apparatus intended for high-pressure liquid chromatography (HPLC)-NMR hyphenation. Some hardware changes were needed to adapt the incompatible flow-rates and a reverse-engineering approach that led to the specific software required to control the apparatus. 1D ¹HNMR and ¹H–¹H correlation spectroscopy (COSY) spectra were acquired in reasonable time without the need for any solvent-suppression method thanks to the SPE nitrogen drying step. The reduced usage of expensive deuterated solvents from several hundreds of milliliters to the milliliter order is the major improvement of this approach compared to the previously published ones

Evolution of Quantitative Measures in NMR: Quantum Mechanical qHNMR Advances Chemical Standardization of a Red Clover (<i>Trifolium pratense</i>) Extract

Chemical standardization, along with morphological and DNA analysis ensures the authenticity and advances the integrity evaluation of botanical preparations. Achievement of a more comprehensive, metabolomic standardization requires simultaneous quantitation of multiple marker compounds. Employing quantitative ¹H NMR (qHNMR), this study determined the total isoflavone content (TIfCo; 34.5–36.5% w/w) via multimarker standardization and assessed the stability of a 10-year-old isoflavone-enriched red clover extract (RCE). Eleven markers (nine isoflavones, two flavonols) were targeted simultaneously, and outcomes were compared with LC-based standardization. Two advanced quantitative measures in qHNMR were applied to derive quantities from complex and/or overlapping resonances: a quantum mechanical (QM) method (QM-qHNMR) that employs ¹H iterative full spin analysis, and a non-QM method that uses linear peak fitting algorithms (PF-qHNMR). A 10 min UHPLC-UV method provided auxiliary orthogonal quantitation. This is the first systematic evaluation of QM and non-QM deconvolution as qHNMR quantitation measures. It demonstrates that QM-qHNMR can account successfully for the complexity of ¹H NMR spectra of individual analytes and how QM-qHNMR can be built for mixtures such as botanical extracts. The contents of the main bioactive markers were in good agreement with earlier HPLC-UV results, demonstrating the chemical stability of the RCE. QM-qHNMR advances chemical standardization by its inherent QM accuracy and the use of universal calibrants, avoiding the impractical need for identical reference materials

Integration of Molecular Networking and <i>In-Silico</i> MS/MS Fragmentation for Natural Products Dereplication

Dereplication represents a key step for rapidly identifying known secondary metabolites in complex biological matrices. In this context, liquid-chromatography coupled to high resolution mass spectrometry (LC-HRMS) is increasingly used and, via untargeted data-dependent MS/MS experiments, massive amounts of detailed information on the chemical composition of crude extracts can be generated. An efficient exploitation of such data sets requires automated data treatment and access to dedicated fragmentation databases. Various novel bioinformatics approaches such as molecular networking (MN) and <i>in-silico</i> fragmentation tools have emerged recently and provide new perspective for early metabolite identification in natural products (NPs) research. Here we propose an innovative dereplication strategy based on the combination of MN with an extensive <i>in-silico</i> MS/MS fragmentation database of NPs. Using two case studies, we demonstrate that this combined approach offers a powerful tool to navigate through the chemistry of complex NPs extracts, dereplicate metabolites, and annotate analogues of database entries

Stilbenoid Profiles of Canes from <i>Vitis</i> and <i>Muscadinia</i> Species

We present stilbenoid profiles of canes from 16 grapevines. Fifteen stilbenoids were obtained through isolation and structure identification using MS, NMR, and [α]_D or as commercial standards. An HPLC–UV method for the simultaneous quantification of nine of these stilbenoids was developed and applied to canes of <i>Vitis amurensis</i>, <i>Vitis arizonica</i>, <i>Vitis berlandieri</i>, <i>Vitis betulifolia</i>, <i>Vitis cinerea</i>, <i>Vitis</i> × <i>champini</i>, <i>Vitis</i> × <i>doaniana</i>, <i>Vitis labrusca</i>, <i>Vitis candicans</i> (syn. <i>Vitis mustangensis</i>), <i>Vitis riparia</i>, <i>Vitis rupestris</i>, <i>Vitis vinifera</i>, <i>Muscadinia rotundifolia</i>, and a <i>V. vinifera</i> × <i>M</i>. <i>rotundifolia</i> hybrid. In these species, <i>E</i>-ampelopsin E, <i>E</i>-amurensin B, <i>E</i>-piceid, <i>E</i>-piceatannol, <i>E</i>-resveratrol, <i>E</i>-resveratroloside, <i>E</i>-ε-viniferin, <i>E</i>-ω-viniferin, and <i>E</i>-vitisin B were quantified, when found in sufficient amounts. Total concentrations ranged from ∼2.2 to 19.5 g/kg of dry weight. Additional stilbenoids, <i>E</i>-3,5,4′-trihydroxystilbene 2-<i>C</i>-glucoside, <i>Z</i>-ampelopsin E, <i>Z</i>-<i>trans</i>-miyabenol C, <i>E</i>-<i>trans</i>-miyabenol C, scirpusin A, and <i>Z</i>-vitisin B, were identified but not quantified. Our results indicate that canes, particularly those of non-<i>vinifera</i> species, have substantial quantities of valuable, health-promoting stilbenoids

Unambiguous Determination of the Absolute Configuration of Dimeric Stilbene Glucosides from the Rhizomes of <i>Gnetum africanum</i>

Dimeric stilbene glucosides <b>1</b>–<b>3</b> [two diastereomers of (−)-gnemonoside A (<b>1a</b> and <b>1b</b>), (−)-gnemonoside C (<b>2</b>), and (−)-gnemonoside D (<b>3</b>)] as well as a mixture of the two enantiomers of gnetin C (<b>4</b>) were isolated from the rhizomes of <i>Gnetum africanum</i>. The two enantiomers of gnetin C, (+)-<b>4</b> and (−)-<b>4</b>, were obtained from the aglycones of <b>1a</b> and <b>1b</b>, respectively. The configurations of these stilbenoids were investigated by NMR and vibrational circular dichroism (VCD) experiments. The absolute configurations of (−)-<b>1a</b>, (−)-<b>2</b>, (−)-<b>3</b>, and (−)-<b>4</b> were established as 7a<i>S</i>,8a<i>S</i> by VCD spectroscopy in combination with density functional theory calculations. The antiamyloidogenic activity of the isolated stilbenes was also evaluated versus beta-amyloid fibrils. The four glucosides of gnetin C (<b>1a</b>, <b>1b</b>, <b>2</b>, and <b>3</b>) were found to be the most active compounds, with inhibition percentages of 56, 56, 58, and 54 at 10 μM, respectively

Subtle Chemical Shifts Explain the NMR Fingerprints of Oligomeric Proanthocyanidins with High Dentin Biomodification Potency

The ability of certain oligomeric proanthocyanidins (OPACs) to enhance the biomechanical properties of dentin involves collagen cross-linking of the 1.3–4.5 nm wide space via protein–polyphenol interactions. A systematic interdisciplinary search for the bioactive principles of pine bark has yielded the trimeric PAC, <i>ent</i>-epicatechin-(4β→8)-epicatechin-(2β→<i>O</i>→7,4β→8)-catechin (<b>3</b>), representing the hitherto most potent single chemical entity capable of enhancing dentin stiffness. Building the case from two congeneric PAC dimers, a detailed structural analysis decoded the stereochemistry, spatial arrangement, and chemical properties of three dentin biomodifiers. Quantum-mechanics-driven ¹H iterative full spin analysis (QM-HiFSA) of NMR spectra distinguished previously unrecognized details such as higher order <i>J</i> coupling and provided valuable information about 3D structure. Detection and quantification of H/D-exchange effects by QM-HiFSA identified C-8 and C-6 as (re)­active sites, explain preferences in biosynthetic linkage, and suggest their involvement in dentin cross-linking activity. Mapping of these molecular properties underscored the significance of high δ precision in both ¹H and ¹³C NMR spectroscopy. Occurring at low- to subppb levels, these newly characterized chemical shift differences in ppb are small but diagnostic measures of dynamic processes inherent to the OPAC pharmacophores and can help augment our understanding of nanometer-scale intermolecular interactions in biomodified dentin macromolecules