A Hexa-Herbal TCM Decoction Used to Treat Skin Inflammation: An LC-MS-Based Phytochemical Analysis

In order to understand the chemical relationship between a traditional hexa-herbal Chinese medicine formula and botanical drugs it is derived from, an analytical platform comprising liquid chromatography coupled with triple quadrupole mass spectrometry and data mining was developed to separate and identify key chemical components. The hexa-herbal formula comprises the rootstock of Scutellaria baicalensis, Rheum tanguticum, Sophora flavescens, the root bark of Dictamnus dasycarpus, the bark of Phellodendron chinense, and the fruit of Kochia scoparia. Seventy-three compounds including alkaloids, anthraquinone derivatives, coumarins, coumarins derivatives, flavonoids, flavone glycosides, naphthalene derivatives, phenylbutanone glucopyranoside, phenolic acids, pterocarpans, stilbenes, stilbenes derivatives, and tannins were putatively identified based on mass measurement and characteristic fragment ions. Among the botanical drugs of the hexa-herbal Chinese medicine formula, the rootstock of R. tanguticum and S. flavescens, bark of P. chinense, and rootstock of S. baicalensis contributed to the majority of the extracted metabolites of the formula decoction. The developed method appeared to be a versatile tool for monitoring chemical constituents in extracts of a traditional Chinese medicine formula in a relatively comprehensive and systematic manner, and helped to understand the importance of the individual botanical drugs within a formulation

Analytic Results for Massless Three-Loop Form Factors

We evaluate, exactly in d, the master integrals contributing to massless three-loop QCD form factors. The calculation is based on a combination of a method recently suggested by one of the authors (R.L.) with other techniques: sector decomposition implemented in FIESTA, the method of Mellin--Barnes representation, and the PSLQ algorithm. Using our results for the master integrals we obtain analytical expressions for two missing constants in the ep-expansion of the two most complicated master integrals and present the form factors in a completely analytic form.Comment: minor revisions, to appear in JHE

Disentangling the Complexity of a Hexa-Herbal Chinese Medicine Used for Inflammatory Skin Conditions—Predicting the Active Components by Combining LC-MS-Based Metabolite Profiles and in vitro Pharmacology

OBJECTIVES: The purpose of this study is to investigate the anti-inflammatory activity of a hexa-herbal Chinese formula (HHCF) using spontaneously immortalized human epidermal keratinocytes (HaCaT) and to predict the active components by correlating the LC-MS-based metabolite profiles of the HHCF and its 12 varied formulae with their anti-inflammatory activity using partial least-squares regression analysis. METHODS: The HHCF comprises the rootstock of Scutellaria baicalensis, Rheum tanguticum, Sophora flavescens, the root bark of Dictamnus dasycarpus, the bark of Phellodendron chinense, and the fruit of Kochia scoparia in equal proportions. Its 12 varied formulae were developed by uniform design with varied proportions of the component botanical drugs. The decoctions of the HHCF and its 12 varied formulae were profiled using liquid chromatography (LC) combined with triple quadrupole mass spectrometry (MS) and their effects on tumor necrosis factor (TNF)-α -plus-interferon (IFN)-γ-induced C-C motif chemokine ligand 17 (CCL17) production in HaCaT were investigated. Partial least-squares regression analysis was conducted to assess the relationship between the LC-MS-based metabolite profiles of the decoctions to anti-CCL17 production in HaCaT. RESULTS: Compounds with potential to promote anti-CCL17 production in HaCaT were identified (e.g., berberine, pyrogallol and catechin dimers) as a result of the developed model and their potential to act as anti-inflammatory agents were also supported by relevant literature. CONCLUSION: This promising approach should assist in the screening process of active components from complex Chinese herbal preparations and will better inform the necessary pharmacological experiments to take forward

InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol in European adult patients : the LIAISON study protocol

The study is funded by Chiesi Farmaceutici S.p.A., Parma, ItalyPeer reviewedPublisher PD

Effectiveness of physical training for self-employed persons with musculoskeletal disorders: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Despite the fact that the population of self-employed persons is still growing and at risk for long term disability due to a number of risk factors, there is still a lack of information on the effectiveness of interventions for this specific group.</p> <p>Methods</p> <p>To determine the effectiveness of physical training without a cognitive behavioral component and workplace specific exercises (PT) and physical training with a cognitive behavioral component and workplace specific exercises (PTCBWE), we conducted a pragmatic Randomized Controlled Trial, stratified into two groups. Self-employed persons with a new work disability claim because of musculoskeletal disorders were randomized to PT (n = 53) or PTCBWE (n = 76), or to a corresponding usual care group (n = 50 and n = 75 respectively). Both types of training consisted of cardiovascular training, strengthening, relaxation and posture exercises and took place two or three times a week, for 1–1.5 hours, during three months, also if someone had already returned to work full-time. The primary outcome measure was claim duration (in days) during 12 months follow-up. Pain severity and functional status were secondary outcome measures. All data were assessed at baseline and at 6 and 12 months follow-up. The data with regard to claim duration were analyzed by survival analysis and Cox regression analysis. Secondary outcome measures were analyzed by means of linear regression analysis.</p> <p>Results</p> <p>After 12 months of follow-up there was no difference in claim duration between PT and usual care (Hazard Ratio 0.7; 95%CI, 0.4–1.1; p = 0.12) or PTCBWE and usual care (Hazard Ratio 0.9; 95%CI, 0.6–1.4; p = 0.72). Both types of physical training and usual care improved in pain and functional status over time, but there was only a statistically significant difference in favor of PT on pain improvement at 6 months.</p> <p>Conclusion</p> <p>In this study, physical training with and without a cognitive behavioral component and workplace specific exercises for self-employed persons with musculoskeletal disorders was not shown to be effective on claim duration, pain severity and functional status at 12 months follow-up.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN67766245.</p

Effectiveness of a questionnaire based intervention programme on the prevalence of arm, shoulder and neck symptoms, risk factors and sick leave in computer workers: A cluster randomised controlled trial in an occupational setting

<p>Abstract</p> <p>Background</p> <p>Arm, shoulder and neck symptoms are very prevalent among computer workers. In an attempt to reduce these symptoms, a large occupational health service in the Netherlands developed a preventive programme on exposure to risk factors, prevalence of arm, shoulder and neck symptoms, and sick leave in computer workers. The purpose of this study was to assess the effectiveness of this intervention programme.</p> <p>Methods</p> <p>The study was a randomised controlled trial. The participants were assigned to either the intervention group or the usual care group by means of cluster randomisation. At baseline and after 12 months of follow-up, the participants completed the RSI QuickScan questionnaire on exposure to the risk factors and on the prevalence of arm, shoulder and neck symptoms. A tailor-made intervention programme was proposed to participants with a high risk profile at baseline. Examples of implemented interventions are an individual workstation check, a visit to the occupational health physician and an education programme on the prevention of arm, shoulder and neck symptoms. The primary outcome measure was the prevalence of arm, shoulder and neck symptoms. Secondary outcome measures were the scores on risk factors for arm, shoulder and neck symptoms and the number of days of sick leave. Sick leave data was obtained from the companies. Multilevel analyses were used to test the effectiveness.</p> <p>Results</p> <p>Of the 1,673 persons invited to participate in the study, 1,183 persons (71%) completed the baseline questionnaire and 741 persons participated at baseline as well as at 12-month follow-up. At 12-month follow-up, the intervention group showed a significant positive change (OR = 0.48) in receiving information on healthy computer use, as well as a significant positive change regarding risk indicators for work posture and movement, compared to the usual care group. There were no significant differences in changes in the prevalence of arm, shoulder and neck symptoms or sick leave between the intervention and usual care group.</p> <p>Conclusions</p> <p>The effects of the RSI QuickScan intervention programme were small, possibly as a result of difficulties with the implementation process of the proposed interventions. However, some significant positive effects were found as to an increase in receiving education and a decrease in exposure to adverse postures and movements. With regard to symptoms and sick leave, only small and non-significant effects were found.</p> <p>Trial registration</p> <p>Netherlands National Trial Register NTR1117</p

Identification of imaging selection patterns in acute ischemic stroke patients and the influence on treatment and clinical trial enrolment decision making

For the STroke Imaging Research (STIR) and VISTA-Imaging Investigators The purpose of this study was to collect precise information on the typical imaging decisions given specific clinical acute stroke scenarios. Stroke centers worldwide were surveyed regarding typical imaging used to work up representative acute stroke patients, make treatment decisions, and willingness to enroll in clinical trials. STroke Imaging Research and Virtual International Stroke Trials Archive-Imaging circulated an online survey of clinical case vignettes through its website, the websites of national professional societies from multiple countries as well as through email distribution lists from STroke Imaging Research and participating societies. Survey responders were asked to select the typical imaging work-up for each clinical vignette presented. Actual images were not presented to the survey responders. Instead, the survey then displayed several types of imaging findings offered by the imaging strategy, and the responders selected the appropriate therapy and whether to enroll into a clinical trial considering time from onset, clinical presentation, and imaging findings. A follow-up survey focusing on 6 h from onset was conducted after the release of the positive endovascular trials. We received 548 responses from 35 countries including 282 individual centers; 78% of the centers originating from Australia, Brazil, France, Germany, Spain, United Kingdom, and United States. The specific onset windows presented influenced the type of imaging work-up selected more than the clinical scenario. Magnetic Resonance Imaging usage (27-28%) was substantial, in particular for wake-up stroke. Following the release of the positive trials, selection of perfusion imaging significantly increased for imaging strategy. Usage of vascular or perfusion imaging by Computed Tomography or Magnetic Resonance Imaging beyond just parenchymal imaging was the primary work-up (62-87%) across all clinical vignettes and time windows. Perfusion imaging with Computed Tomography or Magnetic Resonance Imaging was associated with increased probability of enrollment into clinical trials for 0-3 h. Following the release of the positive endovascular trials, selection of endovascular only treatment for 6 h increased across all clinical vignettes

Localisation of RNAs into the germ plasm of vitellogenic xenopus oocytes

We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2), we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP) particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the “late”, Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others

On the Integrand-Reduction Method for Two-Loop Scattering Amplitudes

We propose a first implementation of the integrand-reduction method for two-loop scattering amplitudes. We show that the residues of the amplitudes on multi-particle cuts are polynomials in the irreducible scalar products involving the loop momenta, and that the reduction of the amplitudes in terms of master integrals can be realized through polynomial fitting of the integrand, without any apriori knowledge of the integral basis. We discuss how the polynomial shapes of the residues determine the basis of master integrals appearing in the final result. We present a four-dimensional constructive algorithm that we apply to planar and non-planar contributions to the 4- and 5-point MHV amplitudes in N=4 SYM. The technique hereby discussed extends the well-established analogous method holding for one-loop amplitudes, and can be considered a preliminary study towards the systematic reduction at the integrand-level of two-loop amplitudes in any gauge theory, suitable for their automated semianalytic evaluation.Comment: 26 pages, 11 figure