12 research outputs found
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, SDā=ā1.4), and 45 received online EMDR (12.4 sessions, SDā=ā0.9). 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 (Nā=ā29), had slightly lower PTSD scores at the end of therapy compared to those who received in-person EMDR (Nā=ā24) (17.1 (SDā=ā3.2) versus 24.5 (SDā=ā3.0), mean differenceā=ā7.8, 95% CI ā0.3, 15.9, pā=ā.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. Clientsā concerns related to lack of privacy and ātransition time/spaceā 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 ā¼200,000 NPs uncovered that NP research follows
power-law characteristics typical for behavioral phenomena. Projection
into occurrenceābioactivityāeffort 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 ā¼200,000 NPs uncovered that NP research follows
power-law characteristics typical for behavioral phenomena. Projection
into occurrenceābioactivityāeffort 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 ā¼5%) 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 <sup>1</sup>HNMR and <sup>1</sup>Hā<sup>1</sup>H 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 <sup>1</sup>H
NMR (qHNMR), this study determined the total isoflavone content (TIfCo;
34.5ā36.5% 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 <sup>1</sup>H 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 <sup>1</sup>H 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 [Ī±]<sub>D</sub> or as commercial standards.
An HPLCāUV 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> Ć <i>champini</i>, <i>Vitis</i> Ć <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> Ć <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>-Īµ-viniferin, <i>E</i>-Ļ-viniferin,
and <i>E</i>-vitisin B were quantified, when found in sufficient
amounts. Total concentrations ranged from ā¼2.2 to 19.5 g/kg
of dry weight. Additional stilbenoids, <i>E</i>-3,5,4ā²-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>ā<b>3</b> [two
diastereomers of (ā)-gnemonoside A (<b>1a</b> and <b>1b</b>), (ā)-gnemonoside C (<b>2</b>), and (ā)-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 (ā)-<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 (ā)-<b>1a</b>, (ā)-<b>2</b>, (ā)-<b>3</b>,
and (ā)-<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 Ī¼M,
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 1.3ā4.5 nm wide space via proteināpolyphenol
interactions. A systematic interdisciplinary search for the bioactive
principles of pine bark has yielded the trimeric PAC, <i>ent</i>-epicatechin-(4Ī²ā8)-epicatechin-(2Ī²ā<i>O</i>ā7,4Ī²ā8)-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 <sup>1</sup>H 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)Āactive 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 Ī“ precision in both <sup>1</sup>H and <sup>13</sup>C 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