High levels of cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6, are associated with chronic diseases like rheumatoid arthritis, asthma, atherosclerosis, Alzheimer's ...disease and cancer; therefore cytokine inhibition might be an important target for the treatment of these diseases. Most drugs used to alleviate some inflammation-related symptoms act by inhibiting cyclooxygenases activity or by blocking cytokine receptors. Nevertheless, these drugs have secondary effects when used on a long-term basis. It has been mentioned that flavonoids, namely quercetin, apigenin and luteolin, reduce cytokine expression and secretion. In this regard, flavonoids may have therapeutical potential in the treatment of inflammation-related diseases as cytokine modulators. This review is focused on current research about the effect of flavonoids on cytokine modulation and the description of the way these compounds exert their effect.
Overgrowth syndromes are characterized by global or localized disproportionate growth associated with other anomalies, including vascular malformations and neurological and/or visceral disorders. ...CLOVES (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined‐type Vascular malformations, Epidermal naevi, Scoliosis/Skeletal and spinal anomalies) is an overgrowth syndrome caused by mosaic activating mutation in gene PIK3CA, which gives rise to abnormal PI3K‐AKT‐mTOR pathway activation. These mutations are responsible for the clinical manifestations of the syndrome, which include low‐ and high‐flow vascular malformations, thoracic lipomatous hyperplasia, asymmetric growth, and visceral and neurological disorders. These common anomalies are illustrated with figures from two personal cases. Identification of the clinical and genetic characteristics of CLOVES syndrome is crucial for the differential diagnosis with other overgrowth syndromes, such as Proteus or Klippel–Trenaunay (K–T) syndromes, and for the therapeutic management of the different anomalies. In this context, a new entity comprising different syndromes with phenotypic mutations in PIK3CA has been proposed, designated PIK3CA‐related overgrowth spectrum (PROS), with the aim of facilitating clinical management and establishing appropriate genetic study criteria.
PIK3CA pathway and syndromes. Left asymmetric overgrowth and sandal gap.
Background and purpose: The present study evaluated the role of CB2 receptors in the regulation of depressive‐like behaviours. Transgenic mice overexpressing the CB2 receptor (CB2xP) were challenged ...with different types of acute and chronic experimental paradigms to evaluate their response in terms of depressive‐like behaviours.
Experimental approach: Tail suspension test (TST), novelty‐suppressed feeding test (NSFT) and unpredictable chronic mild stress tests (CMS) were carried out in CB2xP mice. Furthermore, acute and chronic antidepressant‐like effects of the CB2 receptor‐antagonist AM630 were evaluated by means of the forced swimming test (FST) and CMS, respectively, in wild‐type (WT) and CB2xP mice. CB2 gene expression, brain‐derived neurotrophic factor (BDNF) gene and protein expressions were studied in mice exposed to CMS by real‐time PCR and immunohistochemistry, respectively.
Key results: Overexpression of CB2 receptors resulted in decreased depressive‐like behaviours in the TST and NSFT. CMS failed to alter the TST and sucrose consumption in CB2xP mice. In addition, no changes in BDNF gene and protein expression were observed in stressed CB2xP mice. Interestingly, acute administration of AM630 (1 and 3 mg·kg−1, i.p.) exerted antidepressant‐like effects on the FST in WT, but not in CB2xP mice. Chronic administration of AM630 for 4 weeks (1 mg·kg−1; twice daily, i.p.) blocked the effects of CMS on TST, sucrose intake, CB2 receptor gene, BDNF gene and protein expression in WT mice.
Conclusion and implications: Taken together, these results suggest that increased CB2 receptor expression significantly reduced depressive‐related behaviours and that the CB2 receptor could be a new potential therapeutic target for depressive‐related disorders.
Knowledge about clonal diversity and selection is critical to understand multiple myeloma (MM) pathogenesis, chemoresistance and progression. If targeted therapy becomes reality, identification and ...monitoring of intraclonal plasma cell (PC) heterogeneity would become increasingly demanded. Here we investigated the kinetics of intraclonal heterogeneity among 116 MM patients using 23-marker multidimensional flow cytometry (MFC) and principal component analysis, at diagnosis and during minimal residual disease (MRD) monitoring. Distinct phenotypic subclones were observed in 35/116 (30%) newly diagnosed MM patients. In 10/35 patients, persistent MRD was detected after 9 induction cycles, and longitudinal comparison of patient-paired diagnostic vs MRD samples unraveled phenotypic clonal tiding after therapy in half (5/10) of the patients. After demonstrating selection of distinct phenotypic subsets by therapeutic pressure, we investigated whether distinct fluorescence-activated cell-sorted PC subclones had different clonogenic and cytogenetic profiles. In half (5/10) of the patients analyzed, distinct phenotypic subclones showed different clonogenic potential when co-cultured with stromal cells, and in 6/11 cases distinct phenotypic subclones displayed unique cytogenetic profiles by interphase fluorescence in situ hybridization, including selective del(17p13). Collectively, we unravel potential therapeutic selection of preexisting diagnostic phenotypic subclones during MRD monitoring; because phenotypically distinct PCs may show different clonogenic and cytogenetic profiles, identification and follow-up of unique phenotypic-genetic myeloma PC subclones may become relevant for tailored therapy.
To assess whether the techniques of percutaneous needle electrolysis (PNE) and deep dry needling (DDN) used on trigger points (TrP) of lateral pterygoid muscle (LPM) can significantly reduce pain and ...improve function in patients with myofascial pain syndrome (MPS) compared to a control group treated with a sham needling procedure (SNP).
Sixty patients diagnosed with MPS in the LPM were selected and randomly assigned to one of three groups. The PNE group received electrolysis to the LPM via transcutaneous puncture. The DDN group received a deep puncture to the TrP without the introduction of any substance. In the SNP group, pressure was applied to the skin without penetration. Procedures were performed once per week for 3 consecutive weeks. Clinical evaluation was performed before treatment, and on days 28, 42 and 70 after treatment.
Statistically significant differences (p <0.01) were measured for the PNE and DDN groups with respect to pain reduction at rest, during chewing, and for maximum interincisal opening (MIO). Values for the PNE group showed significantly earlier improvement. Differences for PNE and DDN groups with respect to SNP group were significant (p <0.05) up to day 70. Evaluation of efficacy as reported by the patient and observer was better for PNE and DDN groups. No adverse events were observed for either of the techniques.
PNE and DDN of the LPM showed greater pain reduction efficacy and improved MIO compared to SNP. Improvement was noted earlier in the PNE group than in the DDN group.
One of the main limiting factors in the development of new magnesium (Mg) alloys with enhanced mechanical behavior is the need to use vast experimental campaigns for microstructure and property ...screening. For example, the influence of new alloying additions on the critical resolved shear stresses (CRSSs) is currently evaluated by a combination of macroscopic single-crystal experiments and crystal plasticity finite-element simulations (CPFEM). This time-consuming process could be considerably simplified by the introduction of high-throughput techniques for efficient property testing. The aim of this paper is to propose a new and fast, methodology for the estimation of the CRSSs of hexagonal close-packed metals which, moreover, requires small amounts of material. The proposed method, which combines instrumented nanoindentation and CPFEM modeling, determines CRSS values by comparison of the variation of hardness (H) for different grain orientations with the outcome of CPFEM. This novel approach has been validated in a rolled and annealed pure Mg sheet, whose H variation with grain orientation has been successfully predicted using a set of CRSSs taken from recent crystal plasticity simulations of single-crystal experiments. Moreover, the proposed methodology has been utilized to infer the effect of the alloying elements of an MN11 (Mg–1% Mn–1% Nd) alloy. The results support the hypothesis that selected rare earth intermetallic precipitates help to bring the CRSS values of basal and non-basal slip systems closer together, thus contributing to the reduced plastic anisotropy observed in these alloys.
The perovskite phase of cesium lead iodide (α-CsPbI3 or “black” phase) possesses favorable optoelectronic properties for photovoltaic applications. However, the stable phase at room temperature is a ...nonfunctional “yellow” phase (δ-CsPbI3). Black-phase polycrystalline thin films are synthesized above 330 °C and rapidly quenched to room temperature, retaining their phase in a metastable state. Using differential scanning calorimetry, it is shown herein that the metastable state is maintained in the absence of moisture, up to a temperature of 100 °C, and a reversible phase-change enthalpy of 14.2 (±0.5) kJ/mol is observed. The presence of atmospheric moisture hastens the black-to-yellow conversion kinetics without significantly changing the enthalpy of the transition, indicating a catalytic effect, rather than a change in equilibrium due to water adduct formation. These results delineate the conditions for trapping the desired phase and highlight the significant magnitude of the entropic stabilization of this phase.
The CARMENES radial velocity (RV) survey is observing 324 M dwarfs to search for any orbiting planets. In this paper, we present the survey sample by publishing one CARMENES spectrum for each M ...dwarf. These spectra cover the wavelength range 520–1710 nm at a resolution of at least
R
>80 000, and we measure its RV, H
α
emission, and projected rotation velocity. We present an atlas of high-resolution M-dwarf spectra and compare the spectra to atmospheric models. To quantify the RV precision that can be achieved in low-mass stars over the CARMENES wavelength range, we analyze our empirical information on the RV precision from more than 6500 observations. We compare our high-resolution M-dwarf spectra to atmospheric models where we determine the spectroscopic RV information content,
Q
, and signal-to-noise ratio. We find that for all M-type dwarfs, the highest RV precision can be reached in the wavelength range 700–900 nm. Observations at longer wavelengths are equally precise only at the very latest spectral types (M8 and M9). We demonstrate that in this spectroscopic range, the large amount of absorption features compensates for the intrinsic faintness of an M7 star. To reach an RV precision of 1 m s
−1
in very low mass M dwarfs at longer wavelengths likely requires the use of a 10 m class telescope. For spectral types M6 and earlier, the combination of a red visual and a near-infrared spectrograph is ideal to search for low-mass planets and to distinguish between planets and stellar variability. At a 4 m class telescope, an instrument like CARMENES has the potential to push the RV precision well below the typical jitter level of 3–4 m s
−1
.
Resistant starch (RS) is highly fermentable by microbiota in the colon, resulting in the production of SCFAs. RS is thought to mediate a large proportion of its health benefits, including increased ...satiety, through the actions of SCFAs. The aim of this study was to investigate the effects of a diet high in RS on luminal microbiota composition, luminal SCFA concentrations, and the expression of host genes involved in SCFA uptake, SCFA signaling, and satiety regulation in mucosal tissue obtained from small intestine, cecum, and colon. Twenty adult female pigs were either assigned to a digestible starch (DS) diet or a diet high in RS (34%) for a period of 2 wk. After the intervention, luminal content and mucosal scrapings were obtained for detailed molecular analysis. RS was completely degraded in the cecum. In both the cecum and colon, differences in microbiota composition were observed between DS- and RS-fed pigs. In the colon these included the stimulation of the healthy gut-associated butyrate-producing Faecalibacterium prausnitzii, whereas potentially pathogenic members of the Gammaproteobacteria, including Escherichia coli and Pseudomonas spp., were reduced in relative abundance. Cecal and colonic SCFA concentrations were significantly greater in RS-fed pigs, and cecal gene expression of monocarboxylate transporter 1 (SLC16A1) and glucagon (GCG) was induced by RS. In conclusion, our data show that RS modulates microbiota composition, SCFA concentrations, and host gene expression in pig intestine. Combined, our data provide an enhanced understanding of the interaction between diet, microbiota, and host.
Summary
Background
Capillary malformation–arteriovenous malformation (CM‐AVM) syndrome is a rare syndrome with characteristic skin lesions that are associated with fast‐flow vascular malformations ...(FFVMs) in one‐third of patients. Few case series have been described, and none in Spain.
Aim
To identify the prevalence of dermatological parameters, FFVMs and associated features in a large series of patients with CM‐AVM.
Methods
We conducted an observational study of patients with CM‐AVM syndrome diagnosed in 15 Spanish hospitals over 3 years. The main clinical, radiological, genetic findings and associated diseases were analysed.
Results
In total, 64 patients were assessed. In 26.5% of cases, the diagnosis was incidental. In 75% of patients, there was one significantly larger macule, which we termed the ‘herald patch’. FFVMs were detected in 34% of the patients, with 30% located on the skin, 7.8% in the brain and in 1.5% in the spine. There was a positive family history in 65% of the 64 patients. Genetic analysis was performed for RASA1 mutations in 57 patients, of whom 42 (73%) had a positive result. All 4 patients tested for EPHB4 mutations had a positive result. No tumour lesions were detected in the series, except for five infantile haemangiomas.
Conclusions
Our data on clinical lesions, associated FFVM, family history and genetics are similar to those previously published in the literature. An extensive data analysis failed to demonstrate any statistically significant association between the presence of an FFVM and any clinical, familial or genetic parameter that could predict its onset, although a link between the presence of a herald patch on the midline face and the presence of a brain FFVM was observed. We did not detect any genotype–phenotype correlation.
PDF
