Cu-BTC Functional Microdevices as Smart Tools for Capture and Preconcentration of Nerve Agents

Cu-based metal-organic framework (MOF) microdevices are applied in sampling and preconcentration of nerve agents (NAs) diluted in gaseous streams. An in situ electrochemical-assisted synthesis of a Cu-benzene-1, 3, 5-tricarboxylate (BTC) thick film is carried out to functionalize a Cu-modified glass substrate. This simple, rapid, reproducible, and easy-to-integrate MOF synthesis approach enables the microfabrication of functional micro-preconcentrators with a large Brunauer-Emmett-Teller (BET) surface area (above 2000 cm2) and an active pore volume (above 90 nL) for the efficient adsorption of nerve agent molecules along the microfluidic channel 2.5 cm in length. The equilibrium adsorption capacity of the bulk material has been characterized through thermogravimetric analysis after exposure to controlled atmospheres of a sarin gas surrogate, dimethyl methylphosphonate (DMMP), in both dry and humid conditions (30% RH at 293 K). Breakthrough tests at the ppm level (162 mg/m3) reveal equilibrium adsorption capacities up to 691 mg/g. The preconcentration performance of such µ-devices when dealing with highly diluted surrogate atmosphere, i.e., 520 ppbV (2.6 mg/m3) at 298 K, leads to preconcentration coefficients up to 171 for sample volume up to 600 STP cm3. We demonstrate the potentialities of Cu-BTC micro-preconcentrators as smart first responder tools for "on-field" detection of nerve agents in the gas phase at relevant conditions

Raw and sous-vide-cooked red cardoon stalks (Cynara cardunculus L. var. altilis DC): (poly)phenol bioaccessibility, anti-inflammatory activity in the gastrointestinal tract, and prebiotic activity

The in vitro anti-inflammatory and prebiotic activity and the content and profile of bioaccessible (poly)phenols and catabolites of raw and sous-vide-cooked red cardoon (Cynara cardunculus L. var. altilis DC) were investigated during gastrointestinal (GI) digestion. Raw cardoon after in vitro GI digestion had 0.7% bioaccessible (poly)phenols, which protected against lipopolysaccharide-induced inflammation by counteracting IL-8, IL-6, TNF-α, and IL-10 secretions in differentiated Caco-2 cells. Contrarily, GI-digested sous vide cardoon showed higher (poly)phenol bioaccessibility (59.8%) and exerted proinflammatory effects in Caco-2 cells. (Poly)phenols were highly metabolized during the first 8 h of in vitro fermentation, and nine catabolites were produced during 48 h of fermentation. Colonic-fermented raw and sous-vide-cooked cardoon did not show anti-inflammatory activity in HT-29 cells but presented potential prebiotic activity, comparable to the commercial prebiotic FOS, by stimulating health-promoting bacteria such as Bifidobacterium spp. and Lactobacillus/Enterococcus spp. and by increasing the production of total SCFAs, especially acetate

The rat dorsal column nuclei contain a region homologous to the human Locus K

Locus K is a newly identified region within the territory of the human nucleus cuneatus that shares neurochemical and histological features with protopathic second order sensory nuclei (Del Fiacco et al., 2013; Serra et al., 2013; SIAI 2014). This work is aimed at examining the rat dorsal column nuclei in order to ascertain whether a structure homologous to the human Locus K occurs in the rat brain. Rat brainstem sections were observed by means of ABC and fluorescence immunohistochemistry for neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP), Kluver-Barrera and Nissl staining. Results of the peptide immunoreactive structures in the rat dorsal column nuclei are in general good agreement with findings in previous studies (Hoeflinger et al., 1993). However, at caudalmost levels of the complex, in the territory of the cuneate fascicle and dorsal to the caudal pole of the cuneate nucleus, a small column of gray matter area can be identified that contains a dense plexus of varicose labelled nerve fibres. The observed discrete region has never distinctly described beforehand. Both its position and aspect at neuropeptide-immunoreactivity resemble those of the Locus K we detected in the human dorsal column nuclei, allowing the possibility that it represents the its homologous nucleus in the rat brain. Work funded by Fondazione Banco di Sardegna

Transient receptor potential vanilloid type 1 (TRPV1) and neuropeptides in the dorsal root ganglia and spinal cord in a rat model of Bortezomib-induced neuropathy

Bortezomib (BTZ) is an effective antineoplastic drug that acts by inhibiting the ubiquitin-proteasome cellular pathways. In clinical practice, its chronic administration triggers a significant neurotoxicity, which has been associated with impairment of Aβ, Aδ, and C type primary afferent fibers, though the mechanism underlying its harmful effects remains still to be fully clarified. In order to mimic the clinical use of the drug, we have recently designed an experimental model based on the use of 0,20 mg/kg drug concentration for 8 weeks followed by a follow-up period of 4 weeks. We have previously shown that, in these conditions, a hallmark of neurotoxicity is represented by a small fiber neuropathy, whereas dorsal root ganglia (DRG) neurons did not show any morphological alterations. In order to provide data regarding the mechanism underlying BTZ harmful effects, here we characterize the spinal primary sensory neurons on the basis of their expression of the transient receptor potential vanilloid type-1 (TRPV1) and sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP). In fact, TRPV1 is expressed by sensory neurons where it functions as a molecular integrator for nociception. Its activation causes depolarisation leading to burning pain and release of CGRP and SP which, in turn, activate their effector cell receptors and enhance the sensitization of nociceptors. With this aim, lumbar DRG and spinal cord of BTZ-treated model rats were processed for avidine-biotin-peroxidase complex or fluorescence immunohistochemistry. In the DRG, the immunolabelling for TRPV1 revealed a subpopulation of predominantly small- to medium-sized neurons which appeared more extensive in BTZ-treated rats. Centrally, TRPV1-LI labelled fiber tracts and terminal-like elements distributed in laminae I and II of the dorsal horn where they appeared widely codistributed with both CGRP-LI and SP-LI. With the exception of a slight more intense TRPV1 staining in lamina I of the dorsal horn of BTZ-treated vs control rats, no clear-cut differences in the distribution and amount of immunoreactivity for the three markers could be observed

Mediterranean diet and invasive breast cancer risk in the predimed trial

Trabajo presentado en el X Congreso Internacional de la Dieta Mediterránea, celebrado en Barcelona (España) del 02 al 03 de abril de 2014.[Introduction]: Rates of breast cancer incidence have been rising over the past 3 decades. Dietary factors may play a role in the risk of breast cancer. Some observational cohort studies have suggested that the Mediterranean diet may reduce the risk of breast cancer but no randomized controlled trial had investigated this issue. We aimed to evaluate the effect of two interventions with Mediterranean diet on the primary prevention of breast cancer in a randomized controlled trial. [Methods]: The PREDIMED study (Prevención con Dieta Mediterránea) is a randomized, singleblind, and controlled trial conducted in Spanish primary healthcare centres. Out of 4,282 women recruited (aged 60 to 80 years), 1,478 were assigned to a Mediterranean diet supplemented with extra-virgin olive oil, 1,288 to a Mediterranean diet supplemented with mixed nuts and 1,393 to a control diet (advice to reduce dietary fat). Primary analyses were performed on an intention-to-treat basis. Poisson regression analyses were used to assess the relationship between the nutritional intervention and the incidence of confirmed invasive breast cancer. [Results]: After a median of 4.3 years after randomization, participants in both Mediterranean diet groups (extra-virgin olive oil or nuts) had a 55% relative reduction (95%CI: 9% to 78%) in the risk of invasive breast cancer compared with participants assigned to a control group (with the recommendation to follow a low-fat diet). Observed rates (per 1000 person-years) were 1.14, 1.82 and 2.90 for the Mediterranean diet with extra-virgin olive oil group, the Mediterranean diet supplemented with nuts group and the control group, respectively. The multivariable-adjusted rate ratios versus the control group were 0.34 (95% CI: 0.14 to 0.83) for the Mediterranean diet with extra-virgin olive oil group, and 0.60 (95% CI: 0.26 to 1.35) for the Mediterranean diet supplemented with nuts group. [Conclusions]: This is the first large randomized trial assessing the role of a dietary pattern on breast cancer incidence. Our results suggest that an intervention promoting adherence to the Mediterranean dietary pattern, specially when it is supplemented with extra-virgin olive oil, may contribute to a substantial reduction in the incidence of invasive breast cancer risk in women 60 years and older. However, a longer follow-up of our participants is needed to obtain more precise estimates

Dietary essential oil components in the prevention of hypoperfusion/reperfusion-induced tissue damage in the rat cerebral cortex

To extend our previous observations on the beneficial effect of dietary Pistacia lentiscus L. essential oil during cerebral bilateral common carotid artery occlusioninduced injury, we evaluated the activity of one of its major components, beta-caryophyllene (BCP), already known to possess peculiar biological activities, in Wistar rat cerebral cortex. Cerebral hypoperfusion was produced by a 30 min bilateral common carotid artery occlusion followed by 60 min reperfusion (BCCAO/R). Animals were starved for 12 hours before surgery and, 6 hours prior to hypoperfusion, BCP (40 mg/kg/0, 45 ml of sunflower oil as vehicle) was administered via gavage. Biological samples of brain tissue, plasma and cerebrospinal fluid (CSF) were examined by HPLC, western blot, gel zymography and immunohistochemistry and analyzed for fatty acids, expression of the enzyme ciclooxygenase-2 (COX-2), CB receptors for endocannabinoids (eCBs), and peroxisome proliferator-activated receptor (PPAR)-alpha and enzymatic activity of matrix-metalloprotease-9 (MMP9). Data obtained indicate that BCP appears to influence the outcome of BCCAO/R cerebral injury by modulating changes in levels of polyunsaturated fatty acids, biosynthesis of eCBs and eCB congeners, expression of CB1 and CB2 receptors, COX-2 protein levels and enzymatic activity of MMP9. Brain tissue response to the hypoperfusion/reperfusion-induced cerebral insult is modulated by dietary administration of BCP, suggesting the possible use of this molecule as nutritional treatment in neuroprevention. Work funded by Fondazione Banco di Sardegna

Effect of acute administration of dietary Pistacia lentiscus L. essential oil on the ischemia-reperfusion-induced changes in rat frontal cortex and plasma

In this study Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, was tested for its protective effects in cerebral ischemia/reperfusion-induced injury in Wistar rat frontal cortex and plasma. Cerebral ischemia was produced by a 20 min bilateral common carotid artery occlusion followed by 30 min reperfusion. Pistacia lentiscus L. essential oil (E.O.) (200 mg/0, 45 ml of sunflower oil as vehicle) was administered via gavage 6 hours prior to ischemia. Rats were randomly assigned to four groups, ischemic/reperfused (I/R) and sham-operated rats treated with the vehicle or with E.O.. Different brain areas were analysed for fatty acid changes and expression of the enzyme cyclooxygenase-2 (COX-2). Ischemia/reperfusion triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid (HPUFA) most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of COX-2, as assessed by Western Blot. In plasma of ischemic/reperfused rats, E.O. administration increased both the DHA-to-eicosapentaenoic acid (EPA) ratio and levels of the endocannabinoid congeners palmytoylethanolamide (PEA) and oleoylethanolamide (OEA). The results obtained suggest that ischemia/reperfusion triggers a cerebral insult sufficient to cause a a region specific lipid peroxidation as evidenced by the detectable, significant decrease in the tissue level of DHA, the most abundant essential fatty acid of neuronal membrane phospholipids. Acute dietary pre-treatment with E.O. triggers modifications both in the frontal cortex, where COX-2 expression decreases and the decrease of DHA is apparently prevented, and in plasma, where PEA and OEA levels increase. We suggest that the activity of PEA and OEA, as endogenous ligands of the peroxisome proliferator-activated receptor (PPAR)-alpha, by inducing the peroxisomal beta oxidation, may explain the observed increase in the DHA/EPA ratio. The latter, in fact, might account for an increased metabolism of n-3 aimed at restoring DHA within damaged brain tissue. The possibility that changes in fatty acid metabolism and plasmatic availability of PEA and OEA are correlated events represents an issue worth future investigations

The Effect of a Mediterranean Diet on the Incidence of Cataract Surgery

Background: Cataract is a leading cause of vision impairment worldwide, and surgery is the only available treatment. The process that initiates lens opacification is dependent on the oxidative stress experienced by the lens components. A healthy overall dietary pattern, with the potential to reduce oxidative stress, has been suggested as a means to decrease the risk of developing cataract. We aimed to investigate the hypothesis that an intervention with a Mediterranean diet (MedDiet) rather than a low-fat diet could decrease the incidence of cataract surgery in elderly subjects. Methods: We included 5802 men and women (age range: 55–80 years) from the Prevención con Dieta Mediterránea study (multicenter, parallel-group, randomized controlled clinical trial) who had not undergone cataract surgery. They were randomly assigned to one of three intervention groups: (1) a MedDiet enriched with extra-virgin olive oil (EVOO) (n = 1998); (2) a MedDiet enriched with nuts (n = 1914), and a control group recommended to follow a low-fat diet (n = 1890). The incidence of cataract surgery was recorded yearly during follow-up clinical evaluations. Primary analyses were performed on an intention-to-treat basis. Cox regression analyses were used to assess the relationship between the nutritional intervention and the incidence of cataract surgery. Results: During a follow-up period of 7.0 years (mean follow-up period: 5.7 years; median: 5.9 years), 559 subjects underwent cataract surgery. Two hundred and six participants from the MedDiet + EVOO group, 174 from the MedDiet + Nuts group, and 179 from the control group underwent cataract surgery. We did not observe a reduction in the incidence of cataract surgery in the MedDiet groups compared to the control group. The multivariable adjusted hazard ratios were 1.03 (95% confidence interval [CI]: 0.84–1.26, p = 0.79) for the control group versus the MedDiet + EVOO group and 1.06 (95% CI: 0.86–1.31, p = 0.58) for the control group versus the MedDiet + Nuts group. Conclusions: To our knowledge, this is the first large randomized trial assessing the role of a MedDiet on the incidence of cataract surgery. Our results showed that the incidence of cataract surgery was similar in the MedDiet with EVOO, MedDiet with nuts, and low-fat diet groups. Further studies are necessary to investigate whether a MedDiet could have a preventive role in cataract surgery

Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

The $B_s^0\to J/\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\beta$ measurement from $B^0\to J/\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}$. This is the most precise measurement to date

Model-independent search for CP violation in D0→K−K+π−π+ and D0→π−π+π+π− decays

A search for CP violation in the phase-space structures of D0 and View the MathML source decays to the final states K−K+π−π+ and π−π+π+π− is presented. The search is carried out with a data set corresponding to an integrated luminosity of 1.0 fb−1 collected in 2011 by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. For the K−K+π−π+ final state, the four-body phase space is divided into 32 bins, each bin with approximately 1800 decays. The p-value under the hypothesis of no CP violation is 9.1%, and in no bin is a CP asymmetry greater than 6.5% observed. The phase space of the π−π+π+π− final state is partitioned into 128 bins, each bin with approximately 2500 decays. The p-value under the hypothesis of no CP violation is 41%, and in no bin is a CP asymmetry greater than 5.5% observed. All results are consistent with the hypothesis of no CP violation at the current sensitivity