Normal vision and development in mice with low functional expression of Kir7.1 in heterozygosis for a blindness-producing mutation inactivating the channel.

K+ channel Kir7.1 expressed at the apical membrane of the retinal pigment epithelium (RPE) plays an essential role in retinal function. An isoleucine-to-threonine mutation at position 120 of the protein is responsible for blindness-causing vitreo-retinal dystrophy. We have studied the molecular mechanism of action of Kir7.1-I120T in vitro by heterologous expression and in vivo in CRISPR-generated knockin mice. Full-size Kir7.1-I120T reaches the plasma membrane but lacks any activity. Analysis of Kir7.1 and the I120T mutant in mixed transfection experiments, and that of tandem tetrameric constructs made by combining wild type (WT) and mutant protomers, leads us to conclude that they do not form heterotetramers in vitro. Homozygous I120T/I120T mice show cleft palate and tracheomalacia and do not survive beyond P0, whereas heterozygous WT/I120T develop normally. Membrane conductance of RPE cells isolated from WT/WT and heterozygous WT/I120T mice is dominated by Kir7.1 current. Using Rb+ as a charge carrier, we demonstrate that the Kir7.1 current of WT/I120T RPE cells corresponds to approximately 50% of that in cells from WT/WT animals, in direct proportion to WT gene dosage. This suggests a lack of compensatory effects or interference from the mutated allele product, an interpretation consistent with results obtained using WT/- hemizygous mouse. Electroretinography and behavioral tests also show normal vision in WT/I120T animals. The hypomorphic ion channel phenotype of heterozygous Kir7.1-I120T mutants is therefore compatible with normal development and retinal function. The lack of detrimental effect of this degree of functional deficit might explain the recessive nature of Kir7.1 mutations causing human eye disease.NEW & NOTEWORTHY Human retinal pigment epithelium K+ channel Kir7.1 is affected by generally recessive mutations leading to blindness. We investigate one such mutation, isoleucine-to-threonine at position 120, both in vitro and in vivo in knockin mice. The mutated channel is inactive and in heterozygosis gives a hypomorphic phenotype with normal retinal function. Mutant channels do not interfere with wild-type Kir7.1 channels which are expressed concomitantly without hindrance, providing an explanation for the recessive nature of the disease.

Recent Progress in Stimuli-Responsive Antimicrobial Electrospun Nanofibers.

Electrospun nanofibrous membranes have garnered significant attention in antimicrobial applications, owing to their intricate three-dimensional network that confers an interconnected porous structure, high specific surface area, and tunable physicochemical properties, as well as their notable capacity for loading and sustained release of antimicrobial agents. Tailoring polymer or hybrid-based nanofibrous membranes with stimuli-responsive characteristics further enhances their versatility, enabling them to exhibit broad-spectrum or specific activity against diverse microorganisms. In this review, we elucidate the pivotal advancements achieved in the realm of stimuli-responsive antimicrobial electrospun nanofibers operating by light, temperature, pH, humidity, and electric field, among others. We provide a concise introduction to the strategies employed to design smart electrospun nanofibers with antimicrobial properties. The core section of our review spotlights recent progress in electrospun nanofiber-based systems triggered by single- and multi-stimuli. Within each stimulus category, we explore recent examples of nanofibers based on different polymers and antimicrobial agents. Finally, we delve into the constraints and future directions of stimuli-responsive nanofibrous materials, paving the way for their wider application spectrum and catalyzing progress toward industrial utilization.

Sublithospheric diamond ages and the supercontinent cycle.

Subduction related to the ancient supercontinent cycle is poorly constrained by mantle samples. Sublithospheric diamond crystallization records the release of melts from subducting oceanic lithosphere at 300-700 km depths1,2 and is especially suited to tracking the timing and effects of deep mantle processes on supercontinents. Here we show that four isotope systems (Rb-Sr, Sm-Nd, U-Pb and Re-Os) applied to Fe-sulfide and CaSiO3 inclusions within 13 sublithospheric diamonds from Juína (Brazil) and Kankan (Guinea) give broadly overlapping crystallization ages from around 450 to 650 million years ago. The intracratonic location of the diamond deposits on Gondwana and the ages, initial isotopic ratios, and trace element content of the inclusions indicate formation from a peri-Gondwanan subduction system. Preservation of these Neoproterozoic-Palaeozoic sublithospheric diamonds beneath Gondwana until its Cretaceous breakup, coupled with majorite geobarometry3,4, suggests that they accreted to and were retained in the lithospheric keel for more than 300 Myr during supercontinent migration. We propose that this process of lithosphere growth-with diamonds attached to the supercontinent keel by the diapiric uprise of depleted buoyant material and pieces of slab crust-could have enhanced supercontinent stability.

Effect of essential oil of Alpinia zerumbet on cardiovascular and autonomic function in rats with isoproterenol induced acute myocardial infarction.

Alpinia zerumbet is a plant popularly used to treat hypertension and anxiety. Studies with Alpinia zerumbet demonstrate antihypertensive and vasodilator effects, among others. The objective of this study was to analyze the effect of essential oil of Alpinia zerumbet (EOAz) on cardiovascular and autonomic function in rats with isoproterenol-induced myocardial infarction. Male Wistar rats (n=32) were equally allocated into four groups: Control, ISO (150mg/kg, subcutaneous), EOAz (100mg/kg by gavage), ISO+EOAz. The rats were evaluated for cardiovascular and, autonomic parameters, electrocardiogram, and infarct size. EOAz was not able to reduce the electrocardiographic variations induced by ISO. Heart rate variability showed a decrease in sympathetic modulation on the heart in the groups treated with EOAz. The cardiopulmonary reflex induced by serotonin invoked a superior blood pressure variation at the 2 µg/kg dose in the EOAz treated groups, while the heart rate variation was significantly higher at the 16 µg/kg dose, when compared to other doses, in all groups, except EOAz+ISO. The sympathetic vagal index was higher in ISO group than in control. EOAz did not reduce the infarct size. We conclude that pretreatment with EOAz does not reverse the hemodynamic and electrocardiographic damage caused by isoproterenol but does reduce sympathetic modulation.

A new family of glutamate-gated chloride channels in parasitic sea louse Caligus rogercresseyi: A subunit refractory to activation by ivermectin is dominant in heteromeric assemblies.

Sea louse ectoparasitosis is a major threat to fish aquaculture. Avermectins such as ivermectin and emamectin have been effectively used against sea louse infestation, but the emergence of resistance has limited their use. A better understanding of the molecular targets of avermectins is essential to the development of novel treatment strategies or new, more effective drugs. Avermectins are known to act by inhibiting neurotransmission through allosteric activation of glutamate-gated chloride channels (GluCls). We have investigated the GluCl subunit present in Caligus rogercresseyi, a sea louse affecting aquaculture in the Southern hemisphere. We identify four new subunits, CrGluCl-B to CrGluCl-E, and characterise them functionally. CrGluCl-A (previously reported as CrGluClα), CrGluCl-B and CrGluCl-C all function as glutamate channel receptors with different sensitivities to the agonist, but in contrast to subunit -A and -C, CrGluCl-B is not activated by ivermectin but is rather antagonised by the drug. CrGluCl-D channel appears active in the absence of any stimulation by glutamate or ivermectin and CrGluCl-E does not exhibit any activity. Notably, the expression of CrGluCl-B with either -A or -C subunits gives rise to receptors unresponsive to ivermectin and showing altered response to glutamate, suggesting that coexpression has led to the preferential formation of heteromers to which the presence of CrGluCl-B confers the property of ivermectin-activation refractoriness. Furthermore, there was evidence for heteromer formation with novel properties only when coexpressing pairs E/C and D/B CrGluCl subtypes. Site-directed mutagenesis shows that three transmembrane domain residues contribute to the lack of activation by ivermectin, most crucially Gln 15' in M2, with mutation Q15'T (the residue present in ivermectin-activated subunits A and C) conferring ivermectin activation to CrGluCl-B. The differential response to avermectin of these Caligus rogercresseyi GluClsubunits, which are highly conserved in the Northern hemisphere sea louse Lepeophtheirus salmonis, could have an influence on the response of these parasites to treatment with macrocyclic lactones. They could serve as molecular markers to assess susceptibility to existing treatments and might be useful molecular targets in the search for novel antiparasitic drugs.

Predictive Model for Preeclampsia Combining sFlt-1, PlGF, NT-proBNP, and Uric Acid as Biomarkers.

N-terminal pro-brain natriuretic peptide (NT-proBNP) and uric acid are elevated in pregnancies with preeclampsia (PE). Short-term prediction of PE using angiogenic factors has many false-positive results. Our objective was to validate a machine-learning model (MLM) to predict PE in patients with clinical suspicion, and evaluate if the model performed better than the sFlt-1/PlGF ratio alone. A multicentric cohort study of pregnancies with suspected PE between 24+0 and 36+6 weeks was used. The MLM included six predictors: gestational age, chronic hypertension, sFlt-1, PlGF, NT-proBNP, and uric acid. A total of 936 serum samples from 597 women were included. The PPV of the MLM for PE following 6 weeks was 83.1% (95% CI 78.5−88.2) compared to 72.8% (95% CI 67.4−78.4) for the sFlt-1/PlGF ratio. The specificity of the model was better; 94.9% vs. 91%, respectively. The AUC was significantly improved compared to the ratio alone [0.941 (95% CI 0.926−0.956) vs. 0.901 (95% CI 0.880−0.921), p < 0.05]. For prediction of preterm PE within 1 week, the AUC of the MLM was 0.954 (95% CI 0.937−0.968); significantly greater than the ratio alone [0.914 (95% CI 0.890−0.934), p < 0.01]. To conclude, an MLM combining the sFlt-1/PlGF ratio, NT-proBNP, and uric acid performs better to predict preterm PE compared to the sFlt-1/PlGF ratio alone, potentially increasing clinical precision.

Selective TASK-1 Inhibitor with a Defined Structure-Activity Relationship Reduces Cancer Cell Proliferation and Viability.

Chemical structures of selective blockers of TASK channels contain aromatic groups and amide bonds. Using this rationale, we designed and synthesized a series of compounds based on 3-benzamidobenzoic acid. These compounds block TASK-1 channels by binding to the central cavity. The most active compound is 3-benzoylamino-N-(2-ethyl-phenyl)-benzamide or F3, blocking TASK-1 with an IC50 of 148 nM, showing a reduced inhibition of TASK-3 channels and not a significant effect on different K+ channels. We identified putative F3-binding sites in the TASK-1 channel by molecular modeling studies. Mutation of seven residues to A (I118A, L122A, F125A, Q126A, L232A, I235A, and L239A) markedly decreased the F3-induced inhibition of TASK-1 channels, consistent with the molecular modeling predictions. F3 blocks cell proliferation and viability in the MCF-7 cancer cell line but not in TASK-1 knockdown MCF-7 cells, indicating that it is acting in TASK-1 channels. These results indicated that TASK-1 is necessary to drive proliferation in the MCF-7 cancer cell line.

Effects of Nb Additions and Heat Treatments on the Microstructure, Hardness and Wear Resistance of CuNiCrSiCoTiNbx High-Entropy Alloys.

In this research, a set of CuNiCrSiCoTi (H-0Nb), CuNiCrSiCoTiNb0.5 (H-0.5Nb) and CuNiCrSiCoTiNb1 (H-1Nb) high-entropy alloys (HEAs) were melted in a vacuum induction furnace. The effects of Nb additions on the microstructure, hardness, and wear behavior of these HEAs (compared with a CuBe commercial alloy) in the as-cast (AC) condition, and after solution (SHT) and aging (AT) heat treatments, were investigated using X-ray diffraction, optical microscopy, and electron microscopy. A ball-on-disc configuration tribometer was used to study wear behavior. XRD and SEM results showed that an increase in Nb additions and modification by heat treatment (HT) favored the formation of BCC and FCC crystal structures (CS), dendritic regions, and the precipitation of phases that promoted microstructure refinement during solidification. Increases in hardness of HEA systems were recorded after heat treatment and Nb additions. Maximum hardness values were recorded for the H-1Nb alloy with measured increases from 107.53 HRB (AC) to 112.98 HRB, and from 1104 HV to 1230 HV (aged for 60 min). However, the increase in hardness caused by Nb additions did not contribute to wear resistance response. This can be attributed to a high distribution of precipitated phases rich in high-hardness NiSiTi and CrSi. Finally, the H-0Nb alloy exhibited the best wear resistance behavior in the aged condition of 30 min, with a material loss of 0.92 mm3.

Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress.

We have evaluated cardiac function and fibrosis in infarcted male Wistar rats treated with MitoQ (50 mg/kg/day) or vehicle for 4 weeks. A cohort of patients admitted with a first episode of acute MI were also analyzed with cardiac magnetic resonance and T1 mapping during admission and at a 12-month follow-up. Infarcted animals presented cardiac hypertrophy and a reduction in the left ventricular ejection fraction (LVEF) and E- and A-waves (E/A) ratio when compared to controls. Myocardial infarction (MI) rats also showed cardiac fibrosis and endoplasmic reticulum (ER) stress activation. Binding immunoglobulin protein (BiP) levels, a marker of ER stress, were correlated with collagen I levels. MitoQ reduced oxidative stress and prevented all these changes without affecting the infarct size. The LVEF and E/A ratio in patients with MI were 57.6 ± 7.9% and 0.96 ± 0.34, respectively. No major changes in cardiac function, extracellular volume fraction (ECV), or LV mass were observed at follow-up. Interestingly, the myeloperoxidase (MPO) levels were associated with the ECV in basal conditions. BiP staining and collagen content were also higher in cardiac samples from autopsies of patients who had suffered an MI than in those who had died from other causes. These results show the interactions between mitochondrial oxidative stress and ER stress, which can result in the development of diffuse fibrosis in the context of MI.

Acute hemodynamic responses from low-load resistance exercise with blood flow restriction in young and older individuals: A systematic review and meta-analysis of cross-over trials.

OBJECTIVE: To summarize the existing evidence on the acute response of low-load (LL) resistance exercise (RE) with blood flow restriction (BFR) on hemodynamic parameters. DATA SOURCES: MEDLINE (via PubMed), EMBASE (via Scopus), SPORTDiscus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science and MedRxiv databases were searched from inception to February 2022. REVIEW METHODS: Cross-over trials investigating the acute effect of LLRE + BFR versus passive (no exercise) and active control methods (LLRE or HLRE) on heart rate (HR), systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure responses. RESULTS: The quality of the studies was assessed using the PEDro scale, risk of bias using the RoB 2.0 tool for cross-over trials and certainty of the evidence using the GRADE method. A total of 15 randomized cross-over studies with 466 participants were eligible for analyses. Our data showed that LLRE + BFR increases all hemodynamic parameters compared to passive control, but not compared to conventional resistance exercise. Subgroup analysis did not demonstrate any differences between LLRE + BFR and low- (LL) or high-load (HL) resistance exercise protocols. Studies including younger volunteers presented higher chronotropic responses (HR) than those with older volunteers. CONCLUSIONS: Despite causing notable hemodynamic responses compared to no exercise, the short-term LL resistance exercise with BFR modulates all hemodynamic parameters HR, SBP, DBP and MBP, similarly to a conventional resistance exercise protocol, whether at low or high-intensity. The chronotropic response is slightly higher in younger healthy individuals despite the similarity regarding pressure parameters.

Dietary Patterns in Pregnancy and Biomarkers of Oxidative Stress in Mothers and Offspring: The NELA Birth Cohort.

Background: Although adherence to the Mediterranean and antioxidant-rich diets during pregnancy is suggested to improve maternal-fetal health by reducing oxidative stress, yet there is no study available. Objective: We examined whether maternal dietary patterns in pregnancy impact the biomarkers of oxidative stress in mothers and their offspring. Methods: Study population included 642 mothers and 335 newborns of the "Nutrition in Early Life and Asthma" (NELA) birth cohort. Maternal diet during pregnancy was assessed by a validated food frequency questionnaire and a priori-defined dietary indices (relative Mediterranean Diet [rMED], alternative Mediterranean Diet [aMED], Dietary Approach to Stop Hypertension [DASH], Alternate Healthy Index [AHEI], and AHEI-2010) were calculated. Biomarkers measured were: hydroperoxides, carbonyl groups, and 8-hydroxydeoxyguanosine (8OHdG) determined in maternal blood and newborn cord blood, and urinary maternal and offspring 15-F2t-isoprostane. Multivariate linear regression models were performed. Results: Maternal rMED score was inversely associated with the maternal levels of 8OHdG at mid-pregnancy (beta per 1-point increase = -1.61; 95% CI -2.82, -0.39) and the newborn levels of hydroperoxides (beta per 1-point increase = -4.54; 95% CI -9.32, 0.25). High vs. low maternal rMED score was marginally associated with the decreased levels of 8OHdG in newborns (beta = -9.17; 95% CI -19.9, 1.63; p for trend 0.079). Maternal DASH score tended to be inversely associated with maternal urinary 15-F2t-isoprostane (beta per 1-point increase = -0.69; 95% CI, -1.44, 0.06). High vs. low maternal AHEI score was associated with reduced offspring urinary levels of 15-F2t-isoprostane (beta = -20.2; 95% CI -38.0, -2.46; p for trend 0.026). Conclusion: These results suggest that maternal adherence to healthy dietary patterns during pregnancy may reduce DNA damage and lipid oxidation in mothers and offspring.

Universal Theory of Light Scattering of Randomly Oriented Particles: A Fluctuational-Electrodynamics Approach for Light Transport Modeling in Disordered Nanostructures.

Disordered nanostructures are commonly encountered in many nanophotonic systems, from colloid dispersions for sensing to heterostructured photocatalysts. Randomness, however, imposes severe challenges for nanophotonics modeling, often constrained by the irregular geometry of the scatterers involved or the stochastic nature of the problem itself. In this Article, we resolve this conundrum by presenting a universal theory of averaged light scattering of randomly oriented objects. Specifically, we derive expansion-basis-independent formulas of the orientation-and-polarization-averaged absorption cross section, scattering cross section, and asymmetry parameter, for single or a collection of objects of arbitrary shape. These three parameters can be directly integrated into traditional unpolarized radiative energy transfer modeling, enabling a practical tool to predict multiple scattering and light transport in disordered nanostructured materials. Notably, the formulas of average light scattering can be derived under the principles of fluctuational electrodynamics, allowing the analogous mathematical treatment to the methods used in thermal radiation, nonequilibrium electromagnetic forces, and other associated phenomena. The proposed modeling framework is validated against optical measurements of polymer composite films with metal-oxide microcrystals. Our work may contribute to a better understanding of light-matter interactions in disordered systems, such as plasmonics for sensing and photothermal therapy, photocatalysts for water splitting and CO2 dissociation, photonic glasses for artificial structural colors, and diffuse reflectors for radiative cooling, to name just a few.

Access to Contraceptive Services in Puerto Rico: An Analysis of Policy and Practice Change Strategies, 2015-2018.

CONTEXT: During the 2016-2017 Zika virus outbreak in Puerto Rico, preventing unintended pregnancy was a primary strategy to reduce Zika-related adverse birth outcomes. The Zika Contraception Access Network (Z-CAN) was a short-term emergency response intervention that used contraception to prevent unintended pregnancy among women who chose to delay or avoid pregnancy. OBJECTIVE: This analysis reports on the identified policy and practice change strategies to increase access to or provision of contraceptive services in Puerto Rico between 2015 and 2018. METHODS: A policy review was conducted to document federal- and territorial-level programs with contraceptive coverage and payment policies in Puerto Rico and to identify policy and practice change. Semistructured interviews with key stakeholders in Puerto Rico were also conducted to understand perceptions of policy and practice change efforts following the Zika virus outbreak, including emergency response, local, and policy efforts to improve contraception access in Puerto Rico. RESULTS: Publicly available information on federal and territorial programs with policies that facilitate access, delivery, and utilization of contraceptive coverage and family planning services in Puerto Rico to support contraceptive access was documented; however, interview results indicated that the implementation of the policies was often limited by barriers and that policy and practice changes as the result of the Zika virus outbreak were short-term. CONCLUSION: Consideration of long-term policy and practice changes related to contraceptive access is warranted. Similar analyses can be used to identify policies, practices, and perceptions in other settings in which the goal is to increase access to contraception or reduce unintended pregnancy.

The Interplay of Mitochondrial Oxidative Stress and Endoplasmic Reticulum Stress in Cardiovascular Fibrosis in Obese Rats.

We have evaluated the role of mitochondrial oxidative stress and its association with endoplasmic reticulum (ER) stress activation in the progression of obesity-related cardiovascular fibrosis. MitoQ (200 µM) was orally administered for 7 weeks to male Wistar rats that were fed a high-fat diet (HFD, 35% fat) or a control diet (CT, 3.5% fat). Obese animals presented cardiovascular fibrosis accompanied by increased levels of extracellular matrix proteins and profibrotic mediators. These alterations were associated with ER stress activation characterized by enhanced levels (in heart and aorta vs. CT group, respectively) of immunoglobulin binding protein (BiP; 2.1-and 2.6-fold, respectively), protein disulfide-isomerase A6 (PDIA6; 1.9-fold) and CCAAT-enhancer-binding homologous protein (CHOP; 1.5- and 1.8-fold, respectively). MitoQ treatment was able to prevent (p < 0.05) these modifications at cardiac and aortic levels. MitoQ (5 nM) and the ER stress inhibitor, 4-phenyl butyric acid (4 µM), were able to block the prooxidant and profibrotic effects of angiotensin II (Ang II, 10-6 M) in cardiac and vascular cells. Therefore, the data show a crosstalk between mitochondrial oxidative stress and ER stress activation, which mediates the development of cardiovascular fibrosis in the context of obesity and in which Ang II can play a relevant role.

Delayed Lubricant Depletion of Slippery Liquid Infused Porous Surfaces Using Precision Nanostructures.

Slippery liquid infused porous surfaces (SLIPS) are an important class of repellent materials, comprising micro/nanotextures infused with a lubricating liquid. Unlike superhydrophobic surfaces, SLIPS do not rely on a stable air-liquid interface and thus can better manage low surface tension fluids, are less susceptible to damage under physical stress, and are able to self-heal. However, these collective properties are only efficient as long as the lubricant remains infused, which has proved challenging. We hypothesized that, in comparison to a nanohole and nanopillar morphology, the "hybrid" morphology of a hole within a nanopillar, namely a nanotube, would be able to retain and redistribute lubricant more effectively, owing to capillary forces trapping a reservoir of lubricant within the tube, while lubricant between tubes can facilitate redistribution to depleted areas. By virtue of recent fabrication advances in spacer defined intrinsic multiple patterning (SDIMP), we fabricated an array of silicon nanotubes and equivalent arrays of nanoholes and nanopillars (pitch, 560 nm; height, 2 µm). After infusing the nanostructures (prerendered hydrophobic) with lubricant Krytox 1525, we probed the lubricant stability under dynamic conditions and correlated the degree of the lubricant film discontinuity to changes in the contact angle hysteresis. As a proof of concept, the durability test, which involved consecutive deposition of droplets onto the surface amounting to 0.5 L, revealed 2-fold and 1.5-fold enhancements of lubricant retention in nanotubes in comparison to nanopillars and nanoholes, respectively, showing a clear trajectory for prolonging the lifetime of a slippery surface.

Oxidative Stress and Vascular Damage in the Context of Obesity: The Hidden Guest.

The vascular system plays a central role in the transport of cells, oxygen and nutrients between different regions of the body, depending on the needs, as well as of metabolic waste products for their elimination. While the structure of different components of the vascular system varies, these structures, especially those of main arteries and arterioles, can be affected by the presence of different cardiovascular risk factors, including obesity. This vascular remodeling is mainly characterized by a thickening of the media layer as a consequence of changes in smooth muscle cells or excessive fibrosis accumulation. These vascular changes associated with obesity can trigger functional alterations, with endothelial dysfunction and vascular stiffness being especially common features of obese vessels. These changes can also lead to impaired tissue perfusion that may affect multiple tissues and organs. In this review, we focus on the role played by perivascular adipose tissue, the activation of the renin-angiotensin-aldosterone system and endoplasmic reticulum stress in the vascular dysfunction associated with obesity. In addition, the participation of oxidative stress in this vascular damage, which can be produced in the perivascular adipose tissue as well as in other components of the vascular wall, is updated.

Household plastic waste habits and attitudes: A pilot study in the city of Valencia.

Bearing in mind that only 42% of plastic packaging post-consumer waste is recycled in Europe, the European Directive 2018/852 established the key target of a 55% plastic packaging waste recycling rate by 2030. For this reason, PlastiCircle, funded by the European Union's Horizon 2020 research and innovation program project, aims to foster the recycling of packaging, improve all stages of the waste collection, and promote responsible consumption. Three European cities have been selected as locations for pilot implementation: Valencia (Spain), Utrecht (The Netherlands) and Alba Iulia (Romania). The main objective of the present study has been to evaluate the participants' opinion and attitudes on plastic recycling. This paper presents the results from the district of San Marcelino in the city of Valencia, the first PlastiCircle pilot to face the challenges of encouraging households to participate more in plastic waste sorting and recycling.

NT-proBNP levels in preeclampsia, intrauterine growth restriction as well as in the prediction on an imminent delivery.

OBJECTIVES: Studies of cardiovascular function in pregnancy have shown inconsistent and, in some cases, contradictory results, particularly regarding cardiac output. While some studies report preeclampsia associated with high cardiac output, other studies suggest that preeclampsia should be further subdivided into women with high or low cardiac output. This study was conducted to examine the NT-proBNP levels in preeclampsia, intrauterine growth restriction, and hypertensive pregnancies without preeclampsia. We also examined N-terminal pro-B natriuretic peptide (NT-proBNP) levels three to four months after delivery, in preeclamptic women as well as the prediction of delivery within 10 days. In a reduced number of preeclamptic women and controls we performed echocardiograms to study their diastolic function. METHODS: We investigated the NT-proBNP levels in 213 subjects with preeclampsia only, 73 with intrauterine growth restriction, 44 with preeclampsia and intrauterine growth restriction, 211 who were hypertensive and 662 unaffected pregnancies (controls). We also performed echocardiograms on 36 preeclampsia and 19 controls before delivery and three to five months after delivery. RESULTS: NT-proBNP levels are higher in early onset preeclampsia than in late onset preeclampsia. Intrauterine growth restriction pregnancies showed a NT-proBNP levels similar to hypertensive and unaffected pregnancies. Compared with healthy pregnancies, women with preterm preeclampsia (<37 gestational weeks) had altered left atrial segments. CONCLUSIONS: We observed that NT-proBNP levels are higher in early onset preeclampsia than in late onset. Moreover, diastolic dysfunction is higher in early onset than in late-onset term preeclampsia. An NT-proBNP value >136 pg/mL has a high positive predictive value for an imminent delivery within 10 days.

New 5-carba-pterocarpans: Synthesis and preliminary antiproliferative activity on a panel of human cancer cells.

Natural pterocarpans and synthetic 5-carba-pterocarpans are isosteres in which the oxygen atom at position 5 in the pyran-ring of pterocarpans is replaced by a methylene group. These 5-carba-analogues were obtained in good yields through the palladium-catalyzed oxyarylation of alcoxy-1,2-dihydronaphthalens with o-iodophenols in PEG-400. They were evaluated on human cancer cell lineages derived respectively from prostate tumor (PC3, IC50 = 11.84 µmol L-1, SI > 12)) and acute myeloid leukemia (HL-60, IC50 = 8.81 µmol L-1, SI > 16), highly incident cancer types presenting resistance against traditional chemotherapeutics. Compound 6c (LQB-492) was the most potent (IC50 = 3.85 µmol L-1, SI > 37) in SF-295 cell lineage (glioblastoma). Such findings suggest that 5-carba-pterocarpan can potentially be new hit compounds for further development of novel antiproliferative agents.