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Sex pheromones play a crucial role in species recognition and reproductive isolation. Despite being largely species-specific in drosophilids, the mechanisms underlying pheromone detection, production, and their influence on mating behavior remain poorly understood. Here, we compare the chemical profiles of Drosophila bipectinata and D. melanogaster, the mating behaviors in both species, as well as the tuning properties of Or67d receptors, which are expressed by neurons in antennal trichoid sensilla at1. Through single sensillum recordings, we demonstrate that the D. bipectinata Or67d-ortholog exhibits similar sensitivity to cis-vaccenyl acetate (cVA) as compared to D. melanogaster but in addition also responds uniquely to (Z)-11-eicosen-1-yl-acetate (Z11-20:Ac), a compound exclusively produced by D. bipectinata males. Through courtship behavior assays we found that, surprisingly, perfuming the flies with Z11-20:Ac did not reveal any aphrodisiacal or anti-aphrodisiacal effects in mating assays. The behavioral relevance of at1 neuron channels in D. bipectinata compared to D. melanogaster seems to be restricted to its formerly shown function as an aggregation pheromone. Moreover, the non-specific compound cVA affected copulation negatively in D. bipectinata and could potentially act as a premating isolation barrier. As both ligands of Or67d seem to govern different behaviors in D. bipectinata, additional neurons detecting at least one of those compounds might be involved. These results underscore the complexity of chemical signaling in species recognition and raise intriguing questions about the evolutionary implications of pheromone detection pathways in Drosophila species., (© 2024. The Author(s).)

Lung type 2 pneumocytes (T2Ps) and alveolar macrophages (AMs) play crucial roles in the synthesis, recycling and catabolism of surfactant material, a lipid/protein fluid essential for respiratory function. The liver X receptors (LXR), LXRα and LXRβ, are transcription factors important for lipid metabolism and inflammation. While LXR activation exerts anti-inflammatory actions in lung injury caused by lipopolysaccharide (LPS) and other inflammatory stimuli, the full extent of the endogenous LXR transcriptional activity in pulmonary homeostasis is incompletely understood. Here, using mice lacking LXRα and LXRβ as experimental models, we describe how the loss of LXRs causes pulmonary lipidosis, pulmonary congestion, fibrosis and chronic inflammation due to defective de novo synthesis and recycling of surfactant material by T2Ps and defective phagocytosis and degradation of excess surfactant by AMs. LXR-deficient T2Ps display aberrant lamellar bodies and decreased expression of genes encoding for surfactant proteins and enzymes involved in cholesterol, fatty acids, and phospholipid metabolism. Moreover, LXR-deficient lungs accumulate foamy AMs with aberrant expression of cholesterol and phospholipid metabolism genes. Using a house dust mite aeroallergen-induced mouse model of asthma, we show that LXR-deficient mice exhibit a more pronounced airway reactivity to a methacholine challenge and greater pulmonary infiltration, indicating an altered physiology of LXR-deficient lungs. Moreover, pretreatment with LXR agonists ameliorated the airway reactivity in WT mice sensitized to house dust mite extracts, confirming that LXR plays an important role in lung physiology and suggesting that agonist pharmacology could be used to treat inflammatory lung diseases., (© 2024. The Author(s).)

A data set of clinical studies of electroencephalogram recordings (EEG) following data acquisition protocols in control individuals (Eyes Closed Wakefulness - Eyes Open Wakefulness, Hyperventilation, and Optostimulation) are quantified with information theory metrics, namely permutation Shanon entropy and permutation Lempel Ziv complexity, to identify functional changes. This work implement Linear mixed-effects models (LMEMs) for confirmatory hypothesis testing. The results show that EEGs have high variability for both metrics and there is a positive correlation between them. The mean of permutation Lempel-Ziv complexity and permutation Shanon entropy used simultaneously for each of the four states are distinguishable from each other. However, used separately, the differences between permutation Lempel-Ziv complexity or permutation Shanon entropy of some states were not statistically significant. This shows that the joint use of both metrics provides more information than the separate use of each of them. Despite their wide use in medicine, LMEMs have not been commonly applied to simultaneously model metrics that quantify EEG signals. Modeling EEGs using a model that characterizes more than one response variable and their possible correlations represents a new way of analyzing EEG data in neuroscience., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Adolescent polycystic ovary syndrome (PCOS) is characterized by androgen excess and oligo-amenorrhea, and often results from ectopic lipid storage due to a mismatch between early adipogenesis and later lipogenesis. Endogenous HOX transcript antisense RNA (HOTAIR) and exogenous pioglitazone are enhancers of subcutaneous adipogenesis, particularly in the gluteofemoral region. The A allele of HOTAIR rs1443512 is an equivalent of a natural knock-down and is, thus, a candidate to influence the distribution of fat mass, and also the redistribution of fat mass by pioglitazone in adolescent PCOS-without-obesity., Subjects and Methods: We performed two post hoc analyses by HOTAIR rs1443512 genotype. In the first, we analyzed the pooled pre-treatment data (auxology; endocrinology; body composition by dual X-ray absorptiometry; abdominal fat distribution by magnetic resonance imaging) of 65 adolescent girls with PCOS-without-obesity in three reported studies (ISRCTN45546616; ISRCTN29234515; ISRCTN11062950). In the second, we analyzed the results of 24 adolescent girls with PCOS-without-obesity, who received pioglitazone (7.5 mg/d for 1 year) as part of a randomized combination treatment (with spironolactone and metformin) in two reported studies (ISRCTN29234515; ISRCTN11062950). All data had been obtained in a blinded-to-genotype way., Results: The pre-treatment data disclosed that the girls-with-A-allele of HOTAIR rs1443512 had developed PCOS with a lower BMI (22.3 ± 2.3 kg/m 2 ; N = 17) than the other girls (24.1 ± 2.7 kg/m 2 ; N = 48), this difference being essentially attributable to a lower fat mass (mean difference 4.6 kg; P < 0.01). On low-dose pioglitazone, girls-with-A-allele (N = 12) raised their fat mass while the other girls (N = 12) did not (total fat mass + 2.2 ± 1.8 kg vs  - 0.9 ± 2.2 kg; P < 0.001), particularly in the gynoid area (gluteofemoral fat + 0.6 ± 0.4 kg vs  - 0.1 ± 0.5 kg; hip circumference + 2.3 ± 1.9 cm vs  - 1.7 ± 3.1 cm; both P < 0.001)., Conclusion: The present findings suggest that the HOTAIR rs1443512 genotype influences not only the distribution of fat mass in adolescent girls with PCOS-without-obesity but also the redistribution of fat mass during prolonged treatment with low-dose pioglitazone., Trial Registration: ISRCTN45546616 ( https://doi.org/10.1186/ISRCTN45546616 ). ISRCTN29234515 ( https://doi.org/10.1186/ISRCTN29234515 ). ISRCTN11062950 ( https://doi.org/10.1186/ISRCTN11062950 )., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Accumulating evidence supports the idea that cancer stem cells (CSCs) are those with the capacity to initiate tumors, generate phenotypical diversity, sustain growth, confer drug resistance, and orchestrate the spread of tumor cells. It is still controversial whether CSCs originate from normal stem cells residing in the tissue or cancer cells from the tumor bulk that have dedifferentiated to acquire stem-like characteristics. Although CSCs have been pointed out as key drivers in cancer, knowledge regarding their physiology is still blurry; thus, research focusing on CSCs is essential to designing novel and more effective therapeutics. The purinergic system has emerged as an important autocrine-paracrine messenger system with a prominent role at multiple levels of the tumor microenvironment, where it regulates cellular aspects of the tumors themselves and the stromal and immune systems. Recent findings have shown that purinergic signaling also participates in regulating the CSC phenotype. Here, we discuss updated information regarding CSCs in the purinergic system and present evidence supporting the idea that elements of the purinergic system expressed by this subpopulation of the tumor represent attractive pharmacological targets for proposing innovative anti-cancer therapies., (© 2023. The Author(s).)

Purpose: To evaluate the effect of different non-osteoporotic drugs on the increase or decrease in the risk of incident fragility fractures (vertebral, humerus or hip) in a cohort of patients diagnosed with osteoporosis on active anti-osteoporotic therapy., Methods: For this retrospective longitudinal study, baseline and follow-up data on prescribed non-osteoporotic treatments and the occurrence of vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression models. The drugs evaluated with a possible beneficial effect were thiazides and statins, while the drugs evaluated with a possible harmful effect were antiandrogens, aromatase inhibitors, proton pump inhibitors, selective serotonin reuptake inhibitors, benzodiazepines, GnRH agonists, thyroid hormones, and oral and inhaled corticosteroids., Results: Logistic regression analyses indicated that no treatment significantly improved fracture risk, with the only treatments that significantly worsened fracture risk being letrozole (OR = 0.18, p-value = 0.03) and oral corticosteroids at doses ≤ 5 mg/day (OR = 0.16, p-value = 0.03) and > 5 mg/day (OR = 0.27, p-value = 0.04)., Conclusion: The potential beneficial or detrimental effects of the different drugs evaluated on fracture risk are masked by treatment with anabolic or antiresorptive drugs that have a more potent action on bone metabolism, with two exceptions: letrozole and oral corticosteroids. These findings may have important clinical implications, as patients receiving these treatments are not fully protected by bisphosphonates, which may imply the need for more potent anti-osteoporotic drugs such as denosumab or teriparatide., (© 2023. The Author(s).)

Microplastics (MPs) represent a serious problem for the environment and for this reason they have been studied in many articles, especially their presence in aquatic environments and soils. MPs have been found in wastewater and sewage sludge from municipal wastewater treatment plants (WWTPs). Most part of the published works have focused on the detection and elimination of MPs in the water line and several reviews have been published in the last years. In addition, the application of sewage sludge produced from WWTPs for agricultural use is known to be a primary source of MPs in soils. However, in the scientific literature less attention has been paid to the sludge and little is known about MPs fate when it is applied in agriculture. This work aims to give a global revision on the most used techniques to identify and detect MPs in sludges, their characteristics and incidence, their effect on sludge treatments and their impact on the environment. As far as we know, there are no standardized protocols for MPs extraction from soil and the possible repercussions on the cultivation of plants are not known. This review evidences that more studies are necessary to stablished standardized protocols and decipher the main mechanisms and the effects of MPs from sewage sludge in the environment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

At household level, clothes washing has been recognised as an emitter of microplastics (MPs) into the environment and it is supposed that dishwashing is also a source of MPs, although little attention has been paid so far. In this work, the emission of MPs released from dishwashing procedures at household level has been studied. The effect of different parameters such as time, temperature and type of detergent has been analysed. In addition, the MP content of tap water has been evaluated in order to determine its contribution to the MPs in dishwasher effluent. Results showed that when the dishwasher was operated empty with a pre-wash programme (15 min and room water temperature), between 207 and 427 MPs were released per load (3 L), whereas this value increased notably with an intensive programme (164 min and water at 70 °C) (1025-1370 MPs per load, 15 L), which highlighted the effect of temperature and time on MP release. Additionally, when a polypropylene lunch box was washed, the number of MPs released increased by 14 ± 3 MPs and 166 ± 12 MPs of total. Finally, the influence of the use of detergent with the dishwasher empty and containing lunch boxes has been studied. With detergent, 35-54% more MPs were released from dishwasher accessories, whereas no additional release took place from lunch boxes. This work shows for the first time the important contribution of domestic dishwashing to MP pollution and the environmental benefits of using more environmentally friendly materials in both dishwashing machine accessories and food utensils., (© 2023. The Author(s).)

Background: Recent studies showed that an early strategy for ventricular tachycardia (VT) ablation resulted in reduction of VT episodes or mortality. Cardiac magnetic resonance (CMR)-derived border zone channel (BZC) mass has proved to be a strong non-invasive predictor of VT in post-myocardial infarction (MI). CMR-guided VT substrate ablation proved to be safe and effective for reducing sudden cardiac death (SCD) and VA occurrence., Methods: PREVENT-VT is a prospective, randomized, multicenter, and controlled trial designed to evaluate the safety and efficacy of prophylactic CMR-guided VT substrate ablation in chronic post-MI patients with CMR-derived arrhythmogenic scar characteristics. Chronic post-MI patients with late gadolinium enhancement (LGE) CMR will be evaluated. CMR images will be post-processed and the BZC mass measured: patients with a BZC mass > 5.15 g will be eligible. Consecutive patients will be enrolled at 3 centers and randomized on a 1:1 basis to undergo a VT substrate ablation (ABLATE arm) or optimal medical treatment (OMT arm). Primary prevention ICD will be implanted following guideline recommendations, while non-ICD candidates will be implanted with an implantable cardiac monitor (ICM). The primary endpoint is a composite outcome of sudden cardiac death (SCD) or sustained monomorphic VT, either treated by an ICD or documented with ICM. Secondary endpoints are procedural safety and efficiency outcomes of CMR-guided ablation., Discussion: In some patients, the first VA episode causes SCD or severe neurological damage. The aim of the PREVENT-VT is to evaluate whether primary preventive substrate ablation may be a safe and effective prophylactic therapy for reducing SCD and VA occurrence in patients with previous MI and high-risk scar characteristics based on CMR., Trial Registration: ClinicalTrials.gov, NCT04675073, registered on January 1, 2021., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Due to processing activity, fruits and vegetables generate notable amounts of wastes at the processing, retail, and consumption level. Following the European goals for reducing food wastes and achieving a circular economy of resources, these biowastes should be valorized. In this work, hydrothermal hydrolysis at different conditions (temperatures, times, waste/water ratio, pH values) were tested to treat for first time; biowastes composed of mixed overripe fruits or vegetables to maximize the extraction of fermentable sugars that can be used as substrates in bioprocesses. Experimental data were fitted by a model based on irreversible first-order reactions, and kinetic constants were obtained. When hydrolysis of fruit wastes was carried out at 135 °C and pH 5 during 40 min, more than 40 g of reducing sugars per 100 g of waste (dry weight) could be obtained (represents an extraction of 97% of total carbohydrates). Concentrations of inhibitor compounds (HMF, furfural, acetic acid) in the hydrolysates were very low and, as example, a fermentation to obtain bioethanol was successfully carried out with an efficiency above 95%. Additionally, the production by hydrothermal treatment of bioactive compounds was investigated and the best results obtained were 92% DPPH inhibition and 12 mg GAE/g (dry weight) for antioxidant activity and phenolic compounds, respectively. These values are similar or even higher than those reported in literature using specific parts of fruits and vegetables., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Here, we report on new data (75 analyses) of plutonium (Pu) isotopes to elucidate activity concentrations, inventories, sources, and their transport from the ocean surface to the seafloor from a collection of six deep-sea sediment cores (depths ranging from 257 to 3739 m) in the southern Gulf of Mexico. Sediment cores collected from the continental shelf and upper slope region of the Gulf of Mexico showed 240 Pu/ 239 Pu ratios of 0.15 to 0.26, and 239+240 Pu-inventories ranging from 14.7 to 33.0 Bq m -2 . Inventories and ratios are consistent with global fallout Pu for this tropical region. In contrast, sediment cores collected from the lower slope region and abyssal plain showed low 240 Pu/ 239 Pu ratios of 0.07 to 0.13 and much lower 239+240 Pu inventories below 6.8 Bq m -2 . This implies that only a small fraction of the expected global fallout Pu has reached the deep-sea sediments. The low 240 Pu/ 239 Pu isotope ratios indicate that fallout from the Nevada testing site was an important source of Pu in deep-sea sediments, and that this Pu was likely more efficiently scavenged from the water column than Pu from global fallout. We estimated that up to 44% of the total inventory of 239+240 Pu in deep-sea sediments is due to the Nevada source. Low values and a progressive decrease of 240 Pu/ 239 Pu ratios and 239+240 Pu inventories with increasing water depth have been previously reported for the Gulf of Mexico. Analysis of Pu isotopes in two sediment traps from the upper slope regions shows 240 Pu/ 239 Pu ratios comparable to those observed in global fallout. These results indicate that global fallout Pu is currently the main source of Pu in sinking particles in the water column. Therefore, a significant fraction of global fallout Pu must still be present, either in a dissolved phase, or as biologically recycled material in the water column, or scavenged on the shelf and shelf break. Our results bring to light important questions on the application of Pu isotopes to establish sediment chronologies in deep-sea sediments, since global fallout features such as the 1963 maximum are not available., (© 2022. The Author(s).)

Purpose: To examine the response to anti-osteoporotic treatment, considered as incident fragility fractures after a minimum follow-up of 1 year, according to sex, age, and number of comorbidities of the patients., Methods: For this retrospective observational study, data from baseline and follow-up visits on the number of comorbidities, prescribed anti-osteoporotic treatment and vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression and an artificial network model., Results: Logistic regression showed that the probability of reducing fractures for each anti-osteoporotic treatment considered was independent of sex, age, and the number of comorbidities, increasing significantly only in males taking vitamin D (OR = 7.918), patients without comorbidities taking vitamin D (OR = 4.197) and patients with ≥ 3 comorbidities taking calcium (OR = 9.412). Logistic regression correctly classified 96% of patients (Hosmer-Lemeshow = 0.492) compared with the artificial neural network model, which correctly classified 95% of patients (AUC = 0.6)., Conclusion: In general, sex, age and the number of comorbidities did not influence the likelihood that a given anti-osteoporotic treatment improved the risk of incident fragility fractures after 1 year, but this appeared to increase when patients had been treated with risedronate, strontium or teriparatide. The two models used classified patients similarly, but predicted differently in terms of the probability of improvement, with logistic regression being the better fit., (© 2022. The Author(s).)

Cancer comprises a collection of diseases that occur in almost any tissue and it is characterized by an abnormal and uncontrolled cell growth that results in tumor formation and propagation to other tissues, causing tissue and organ malfunction and death. Despite the undeniable improvement in cancer diagnostics and therapy, there is an urgent need for new therapeutic and preventive strategies with improved efficacy and fewer side effects. In this context, purinergic signaling emerges as an interesting candidate as a cancer biomarker or therapeutic target. There is abundant evidence that tumor cells have significant changes in the expression of purinergic receptors, which comprise the G-protein coupled P2Y and AdoR families of receptors and the ligand-gated ion channel P2X receptors. Tumor cells also exhibit changes in the expression of nucleotidases and other enzymes involved in nucleotide metabolism, and the concentrations of extracellular nucleotides are significantly higher than those observed in normal cells. In this review, we will focus on the potential role of purinergic signaling in the ten most lethal cancers (lung, breast, colorectal, liver, stomach, prostate, cervical, esophagus, pancreas, and ovary), which together are responsible for more than 5 million annual deaths., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

The current study is focused on the simple synthesis of two novel biosorbent beads: BASB/STMP and CNFB/STMP, derived respectively from bleached almond shell (BAS) and cellulose nanofiber from almond shell (CNF) by means of chemical crosslinking with sodium trimetaphosphate (STMP). These biosorbents were thoroughly characterized in terms of structure (FTIR), texture (N 2 adsorption-desorption), thermal behavior (TGA/DTG), morphology (SEM), and surface properties (XPS). The adsorption kinetics of Cu(II) ions onto BASB/STMP and CNFB/STMP materials proved the chemisorption interaction between Cu(II) ions and the STMP functionalized beads. The BASB/STMP equilibrium data were successfully described by the Redlich-Peterson model and the CNFB/STMP data by the Sips model which disclosed maximum adsorption capacities of 141.44 mg g -1 and 147.90 mg g -1 , respectively. Furthermore, the BASB/STMP bioadsorbent offers easy regeneration and better reusability with high efficiency (> 83%). This study sheds light on the preparation of low-cost adsorbents for wastewater treatment in order to improve the competitiveness and eco-friendliness of agrowaste-based processes., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background Palbociclib and ribociclib are novel oral agents in hormone receptor-positive metastatic breast cancer. Neutropenia is a common adverse event associated with these treatments and its clinical management often requires regimen changes, such as cycle delays and dose adjustments. Objective To provide a real-world experience of the effectiveness and toxicities associated with these drugs and to evaluate the impact of regimen changes in disease progression. Setting This study was performed at Hospital Universitario La Paz, in Spain. Methods Observational, retrospective study which included hormone receptor-positive metastatic breast cancer patients who initiated treatment with palbociclib or ribociclib between March 1st, 2018 and March 1st, 2019. Main outcome measure The primary effectiveness variable was progression-free survival. Safety evaluation was performed to determine neutropenia-incidence and severity, as well as its clinical management, including dose adjustments and treatment interruptions. Correlations between these regimen changes and effectiveness were also evaluated. Results Sixty-one patients were included, 33 treated with palbociclib and 28 with ribociclib. Palbociclib was mainly used as second line of treatment in the metastatic setting (81.8%) and ribociclib as first line (67.9%). The median progression-free survival was 12.76 months (95% CI 7.5 to not estimable) in palbociclib and not reached in ribociclib. After 12 months, the progression-free survival rate was 51.5% (95% CI 34-69) in palbociclib and 78.6% (95% CI 63-94.1) in ribociclib. Neutropenia was the most common adverse event with an incidence rate of 87.9% in palbociclib and 82.1% in ribociclib. Cycle delays were needed in more than half of the patients treated with palbociclib and ribociclib (63.6% and 64.3%). Dose adjustments were seen in 42.4% and 53.6% of the patients receiving palbociclib and ribociclib, respectively. Regimen changes did not involve statistically significant differences in 12-month PFS rates in the cohort investigated. Conclusion Palbociclib and ribociclib outcomes are comparable to those reached in the phase III trials, PALOMA-3 and MONALEESA-2, respectively, and cannot be compared as they were used in different treatment settings. The toxicity profile is favourable, being neutropenia the most common adverse event, easily managed with regimen changes. Further studies are needed to confirm the observed tendency of no detrimental impact on effectiveness of these regimen changes., (© 2020. Springer Nature Switzerland AG.)

The aim of this research was to measure enteric methane (CH 4 ) emissions by young Brahman bulls grazing tropical pastures at different rainfall seasons in the Peruvian jungle. Fourteen 1.5-year-old, young bulls (280 kg ± 18 kg BW) were grazed on tropical grasses and legumes dominated by German grass [Echinochloa polystachya (Kunth) Hitch.] and minor proportion of Torourco grass [Paspalum conjugatum (P.J. Bergius) Roxb] and Leguminous Calopo (Calopogonium mucunoides Desv.) and Kudzú [Pueraria phaseoloides (Roxb.) Benth]. Enteric CH 4 emission was measured by the sulfur hexafluoride (SF 6 ) tracer-gas technique. Organic matter intake (OMI) was determined from organic matter digestibility (OMD) using a fecal protein crude index and fecal output estimated by the dosage of external markers. There was a difference in OMD between seasons (68 and 66% for the dry and rainy seasons, respectively; P < 0.0001). The OMI (6.7 and 7.4 kg/day) and CH4 (178.7 and 298 g/day) were higher (P < 0.05) in the dry season than in the rainy season, respectively. The yield of CH 4 was lower (P < 0.0001) during rainy season (7.1%) than at the dry season (10.6%). The CH 4 emission (g/day) was correlated with OMD (%) (r = 0.74, P < 0.0001). Enteric CH 4 emissions of young bulls grazing mixtures of tropical pastures were significantly lower in animals grazing on the rainy-season, expressed either through unit of absolute emission, intake or as percentage of the GEI. Likewise, OMD of consumed pasture was the most important factor determining CH 4 emission., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: There is a significant relationship between childhood trauma and the development of an eating disorder in adolescence or adulthood, possibly influenced by circulating levels of inflammatory parameters. The main objective is to identify and describe a subgroup of patients with eating disorders and a history of trauma in childhood or adolescence with differential clinical features., Methods: An observational study on a sample of 55 patients who met the diagnostic criteria for any DSM-5 eating disorder was carried out. Inflammatory parameters in white blood cells were examined. Patients underwent different assessments, including clinical and personality scales., Results: Patients with a history of trauma had higher scores in the delirious and narcissistic items of the Millon Clinical Multiaxial Inventory (MCMI-II) (p < 0.05) and a higher score in the paranoid item of the SCID-5 Personality Disorders Version (SCID-5-PD) (p < 0.05). Patients with distinguishing personality features were grouped according to the Childhood Trauma Questionnaire sexual subscale. Tumor necrosis alpha (TNF-α) showed a significant association with childhood trauma history., Conclusions: There is a profile of patients with eating disorders who have increased activity in the inflammatory pathways that, if identified precociously, can benefit from specifically aimed interventions., Level of Evidence: Level V, observational study.

Mountain wines produced in specific mountain areas and following singular practices have gained popularity over the last few decades. During this time, the environmental impacts associated with the food and beverage manufacturing sector have become a question of interest. However, the environmental impacts derived from the production of this peculiar wine have scarcely been studied until now. A mountain winery in north Spain has been analyzed as representative of PDO "Cangas" winemaking by means of life cycle assessment (LCA). High-quality inventory data for one year of operation was obtained directly from this facility and two steps have been considered, the vineyard and the winery phases. The main factors involved in grape cultivation and wine production were included. In common with standard winemaking processes, the use of fertilizers and the production of glass bottles were the principal hotspots in the grape cultivation and wine production phases, respectively. Additionally, in the winery here evaluated, waste management also contributed notably to several impacts, mainly due to the employment of traditional practices such as the incineration in situ of vineyard pruning wastes. The carbon footprint obtained for "Cangas" PDO wine was 2.35 kg of CO 2 eq per 0.75-l bottle, a value within the range reported in the literature for different wines around the world (0.2-2.5 kg CO 2 eq per bottle). A sensitivity analysis has shown that changes in vineyard productivity and the amount of fertilizers applied to the land would strongly affect the environmental performance of the wine manufacturing process. Some alternative scenarios have been proposed, modifying the management of pruning wastes in the vineyard and the packaging material in the winery. Results showed that environmental impacts associated with the production of this mountain wine could be notably reduced simply by reusing a percentage of the bottles and/or composting the organic wastes. Specifically, the carbon footprint would be 40% lower if these two improvements were implemented. Considering the lack of similar studies, further research on the production of mountain wines should be carried out in other regions to increase the knowledge about the environmental impacts associated with the manufacturing of this singular type of wine.

In this study, novel cellulose-bead-based biosorbents (CBBAS) were successfully synthesized from almond shell using a simple three-step process: (i) dissolution of bleached almond shell in ionic liquid (1-butyl-3-methylimidazolium chloride), (ii) coagulation of cellulose-ionic liquid solution in water and (iii) freeze-drying. Their morphological, structural and physicochemical properties were thoroughly characterized. These biomaterials exhibited a 3D-macroporous structure with interconnected pores, which provided a high number of adsorption sites. It should be noted that CBBAS biosorbents were efficiently employed for the removal of copper (II) ions from aqueous solutions, showing high adsorption capacity: 128.24 mg g -1 . The biosorption equilibrium data obtained were successfully fitted to the Sips model and the kinetics were suitably described by the pseudo-second-order model. Besides, CBBAS biosorbents can be easily separated from the solution for their subsequent reuse, and thus, they represent a method for the removal of copper (II) from aqueous solutions that is not only eco-friendly but also economical.

Quantum dots (QDs) are a special type of engineered nanomaterials with outstanding optoelectronic properties that make them as a very promising alternative to conventional luminescent dyes in biomedical applications, including biomolecule (BM) targeting, luminescence imaging and drug delivery. A key parameter to ensure successful biomedical applications of QDs is the appropriate surface modification, i.e. the surface of the nanomaterials should be modified with the appropriate functional groups to ensure stability in aqueous solutions and it should be conjugated with recognition elements capable of ensuring an efficient tagging of the BMs of interest. In this review we summarize the most relevant strategies used for surface modification of QDs and for their conjugation to BMs in preparation of their application in nanoplatforms for luminescent BM sensing and imaging-guided targeting. The applications of conjugations of photoluminescent QDs with different BMs in both in vitro and in vivo chemical sensing, immunoassays or luminescence imaging are reviewed. Recent progress in the application of functionalized QDs in ultrasensitive detection in bioanalysis, diagnostics and imaging strategies are reported. Finally, some key future research goals in the progress of bioconjugation of QDs for diagnosis are identified, including novel synthetic approaches, the need for exhaustive characterization of bioconjugates and the design of signal amplification schemes.

Milk production has been estimated to contribute 3-4% of anthropogenic greenhouse gas (GHG) emissions. However, the carbon footprint associated with raw milk can vary, depending on a variety of factors, such as the geographical area, species of cow and production system. In this study, a global overview of research published on the carbon footprint (CF) of raw cow milk is provided. Additionally, two different dairy systems (semi-confinement and pasture-based) have been analysed by life-cycle assessment (LCA) in order to determine their effect on the CF of the milk produced. Inventory data were obtained directly from these facilities, and the main factors involved in milk production were included (co-products, livestock food, water, electricity, diesel, cleaning elements, transport, manure and slurry management, gas emissions to air etc.). In agreement with reviewed literature, it was found that the carbon footprint of milk was basically determined by the cattle feeding system and gas emissions from the cows. The values of milk CF found in the systems under study were within the range for cow milk production worldwide (0.9-4.7 kgCO 2 eq kg FPCM -1 ). Specifically, in the semi-confinement and the pasture-based dairy farms, 1.22 and 0.99 kgCO 2 eq kg FPCM -1 were obtained, respectively. The environmental benefits obtained with the pasture grazing system are not only mainly due to the lower use of purchased fodder but also to the allocation between milk and meat that was found to be a determining methodological factor in CF calculation. Finally, data from the evaluated dairy systems have been employed to analyse the influence of raw milk production on cheese manufacturing. With this aim, the CF of a small-scale cheese factory has also been obtained. The main subsystems involved (raw materials, water, electricity, energy, cleaning products, packaging materials, transport, wastes and gas emissions) were included in the inventory of the cheese factory. CF values were 16.6 and 14.7 kgCO 2 eq kg -1 of cheese for milk produced in semi-confinement and pasture-based systems, respectively. The production of raw milk represented more than 60% of CO 2 eq emissions associated with cheese, so the primary production is the critical factor in reducing the GHG emissions due to cheese making.

Purpose: Pulmonary vein (PV) isolation (PVI) by point-by-point radiofrequency application (PPRF) results in longer procedures than that achieved by single-shot ablation techniques. In addition, it is associated with significant risk of oesophageal injury. The POWER-FAST pilot study evaluated the feasibility and safety of PVI by high-power short-duration (HPSD) PPRF., Methods: HPSD PPRF around the PVs was done in 48 consecutive patients with atrial fibrillation. Fifty watts was delivered until a predefined lesion index value was reached (LSI ≥ 5 or Abl-I ≥ 350) and 60 W during 7-10 s in the first 18 and last 30 patients, respectively. A control group of 47 consecutive patients who had undergone PVI before the HPSD group with conventional PPRF (30 W for 30 s) was included for reference. Echocardiography and oesophageal endoscopy was performed shortly after ablation in all patients., Results: PVI of all targeted veins was achieved in 98% and 100% of patients of the conventional and HPSD groups, respectively (p = 0.59). Total radiofrequency time was 34 ± 11, 24 ± 8, and 15 ± 5 min in groups 30 W, 50 W, and 60 W (p < 0.001). Audible steam pops occurred in 4 out of 48 (8%) patients in the HPSD group, accounting for 4 (0.08%) out of 5 269 HPSD radiofrequency applications. No patient in the HPSD group developed pericardial effusion. The incidence of oesophageal lesions was 28%, 22%, and 0% in groups 30 W, 50 W, and 60 W, respectively (p = 0.007) CONCLUSIONS: PVI can be achieved with HPSD PPRF in most patients. This approach appears safe and associated with low risk of esophageal damage.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a pleiotropic transcription factor that has neuroprotective and anti-inflammatory effects, regulating more than 250 genes. As NRF2, cannabinoid receptor type 2 (CB 2 ) is also implicated in the preservation of neurons against glia-driven inflammation. To this concern, little is known about the regulation pathways implicated in CB 2 receptor expression. In this study, we analyze whether NRF2 could modulate the transcription of CB 2 in neuronal and microglial cells. Bioinformatics analysis revealed an antioxidant response element in the promoter sequence of the CB 2 receptor gene. Further analysis by chemical and genetic manipulations of this transcription factor demonstrated that NRF2 is not able to modulate the expression of CB 2 in neurons. On the other hand, at the level of microglia, the expression of CB 2 is NRF2-dependent. These results are related to the differential levels of expression of both genes regarding the brain cell type. Since modulation of CB 2 receptor signaling may represent a promising therapeutic target with minimal psychotropic effects that can be used to modulate endocannabinoid-based therapeutic approaches and to reduce neurodegeneration, our findings will contribute to disclose the potential of CB 2 as a novel target for treating different pathologies.

Extracellular purines (ATP and adenosine) are ubiquitous intercellular messengers. During tissular damage, they function as damage-associated molecular patterns (DAMPs). In this context, purines announce tissue alterations to initiate a reparative response that involve the formation of the inflammasome complex and the recruitment of specialized cells of the immune system. The present review focuses on the role of the purinergic system in liver damage, mainly during the onset and development of fibrosis. After hepatocellular injury, extracellular ATP promotes a signaling cascade that ameliorates tissue alterations to restore the hepatic function. However, if cellular damage becomes chronic, ATP orchestrates an aberrant reparative process that results in severe liver diseases such as fibrosis and cirrhosis. ATP and adenosine, their receptors, and extracellular ectonucleotidases are mediators of unique processes that will be reviewed in detail.

Objective: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries., Methods: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs., Results: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016., Conclusion: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

A prospective, descriptive observational study of consecutive patients treated with ceftolozane/tazobactam in the reference hospital of the Balearic Islands (Spain), between May 2016 and September 2017, was performed. Demographic, clinical, and microbiological variables were recorded. The later included resistance profile, molecular typing, and whole genome sequencing of isolates showing resistance development. Fifty-eight patients were treated with ceftolozane/tazobactam. Thirty-five (60.3%) showed respiratory tract infections, 21 (36.2%) received monotherapy, and 37 (63.8%) combined therapy for ≥ 72 h, mainly with colistin (45.9%). In 46.6% of the patients, a dose of 1/0.5 g/8 h was used, whereas 2/1 g/8 h was used in 41.4%. In 56 of the cases (96.6%), the initial Pseudomonas aeruginosa isolates recovered showed a multidrug resistant (MDR) phenotype, and 50 of them (86.2%) additionally met the extensively drug resistant (XDR) criteria and were only susceptible colistin and/or aminoglycosides (mostly amikacin). The epidemic high-risk clone ST175 was detected in 50% of the patients. Clinical cure was documented in 37 patients (63.8%) and resistance development in 8 (13.8%). Clinical failure was associated with disease severity (SOFA), ventilator-dependent respiratory failure, XDR profile, high-risk clone ST175, negative control culture, and resistance development. In 6 of the 8 cases, resistance development was caused by structural mutations in AmpC, including some mutations described for the first time in vivo, whereas in the other 2, by mutations in OXA-10 leading to the extended spectrum OXA-14. Although further clinical experience is still needed, our results suggest that ceftolozane/tazobactam is an attractive option for the treatment of MDR/XDR P. aeruginosa infections.

Flow cytometry has recently been presented as a research tool in the assessment of the viability/activity of activated sludge from municipal wastewater treatment plants, but it has not put in practice for industrial biotreatments yet. In this study, for the first time ever, the reliability and significance of the multiparameter flow cytometry applied to the biological nitrification-denitrification treatment of leachate have been evaluated. Using a double staining procedure (cFDA/PI), the viable, damaged, and dead subpopulations were determined, and the results were compared to those obtained with conventional methods, such as nitrogen and oxygen uptake rates or plate counting. Flow cytometry showed that viable cells represented approximately 47% of the total population, whereas active cells accounted for 90%. For both sludge from nitrification and denitrification processes, with less than 1% of them being also culturable in plate. Either flow cytometry or uptake rates revealed that health status of sludge remained constant throughout the biotreatment, which is consistent with the high recirculation rates. Under anaerobic starvation conditions, physiological status of sludge remained constant as well as specific oxygen and denitrification rates. Nevertheless, both the culturability in plate and the nitrification rate significantly decreased. These findings proved that multiparameter flow cytometry is a useful tool for the assessment of the viability and activity of sludge from a nitrification-denitrification biotreatment process. These results gathered all the bacterial communities in the sludge, so the decay in minority populations, such as nitrifying bacteria, requires the use of a complementary technique to evaluate specific activities.

Hyaluronan (HA) is the major glycosaminoglycan present in the extracellular matrix. It is produced by some tumours and promotes proliferation, differentiation and migration among others cellular processes. Gestational trophoblastic disease (GTD) is composed by non-tumour entities, such as hydatidiform mole (HM), which is the most common type of GTD and also malignant entities such as choriocarcinoma (CC) and placental site trophoblastic tumour (PSTT), being CC the most aggressive tumour. Although there is a growing understanding of GTD biology, the role of HA in the pathogenesis of this group of diseases remains largely unknown. The aim of this work was to study the role of HA in the pathogenesis of GTD by defining the expression pattern of HA and its receptors CD44 and RHAMM, as well as to determine if HA can modulate proliferation, differentiation and migration of CC cells. Receptors and signalling pathways involved were also analyzed. We demonstrated that HA and RHAMM are differently expressed among GTD entities and even among trophoblast subtypes. We also showed that HA is able to enhance the expression of extravillous trophoblast markers and also to induce migration of JEG-3 cells, the latter mediated by RHAMM as well as PI3K and MAPK pathways. These findings indicate a novel regulatory mechanism for CC cell biology and also contribute to the understanding of GTD pathophysiology.

The epithelium-mesenchymal transition (EMT) is an important process of cell plasticity, consisting in the loss of epithelial identity and the gain of mesenchymal characteristics through the coordinated activity of a highly regulated informational program. Although it was originally described in the embryonic development, an important body of information supports its role in pathology, mainly in cancerous and fibrotic processes. The purinergic system of inter-cellular communication, mainly based in ATP and adenosine acting throughout their specific receptors, has emerged as a potent regulator of the EMT in several pathological entities. In this context, cellular signaling associated to purines is opening the understanding of a new element in the complex regulatory network of this phenotypical differentiation process. In this review, we have summarized recent information about the role of ATP and adenosine in EMT, as a growing field with high therapeutic potential.

Chronic myeloid leukemia (CML) is a myeloproliferative syndrome characterized by the presence of the Philadelphia chromosome which encodes a constitutively activated tyrosine kinase (BCR-ABL). The first line treatment for CML consists on BCR-ABL inhibitors such as Imatinib. Nevertheless, such treatment may lead to the selection of resistant cells. Therefore, it is of great value to find molecules that enhance the anti-proliferative effect of first-line drugs. Hyaluronan is the main glycosaminglican of the extracellular matrix which is involved in tumor progression and multidrug resistance. We have previously demonstrated that the inhibition of hyaluronan synthesis by 4-methylumbelliferone (4MU) induces senescence and can revert Vincristine resistance in CML cell lines. However, the effect of 4MU on Imatinib therapy remains unknown. The aim of this work was to determine whether the combination of 4MU with Imatinib is able to modulate the proliferation as well as apoptosis and senescence induction in human CML cell lines. For this purpose the ATCC cell line K562, and its multidrug resistant derivate, Kv562 were used. Cells were exposed to 4MU, Imatinib or a combination of both. We demonstrated that 4MU and Imatinib co-treatment abrogated the proliferation of both cell lines. However, such co-treatment did not increase the levels of apoptosis when compared with the treatment with Imatinib alone. For both cell lines the mechanisms of tumor suppression involved was senescence, since the combination of 4MU and Imatinib arrested the cell cycle and increased senescence associated β-galactosidase activity and senescence associated heterochromatin foci presence when compared to each drug alone. Moreover, 4MU, Imatinib and 4MU + Imatinib decreased pAkt/Akt ratio in both cell lines and reduced the pERK/ERK ratio only in K562 cells. These findings highlight the potential use of 4MU together with Imatinib for CML therapy.

Background: Accumulating evidence indicates that type 2 diabetes is associated with an increased risk to develop breast cancer. This risk has been attributed to hyperglycemia, hyperinsulinemia and chronic inflammation. As yet, however, the mechanisms underlying this association are poorly understood. Here, we studied the effect of high glucose and insulin on breast cancer-derived cell proliferation, migration, epithelial-mesenchymal transition (EMT) and invasiveness, as well as its relationship to reactive oxygen species (ROS) production and the plasminogen activation system., Methods: MDA-MB-231 cell proliferation, migration and invasion were assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), scratch-wound and matrigel transwell assays, respectively. ROS production was determined using 2' 7'-dichlorodihydrofluorescein diacetate. The expression of E-cadherin, vimentin, fibronectin, urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1) were assessed using qRT-PCR and/or Western blotting assays, respectively. uPA activity was determined using gel zymography., Results: We found that high glucose stimulated MDA-MB-231 cell proliferation, migration and invasion, together with an increased expression of mesenchymal markers (i.e., vimentin and fibronectin). These effects were further enhanced by the simultaneous administration of insulin. In both cases, the invasion and growth responses were found to be associated with an increased expression of uPA, uPAR and PAI-1, as well as an increase in active uPA. An osmolality effect of high glucose was excluded by using mannitol at an equimolar concentration. We also found that all changes induced by high glucose and insulin were attenuated by the anti-oxidant N-acetylcysteine (NAC) and, thus, depended on ROS production., Conclusions: From our data we conclude that hyperglycemia and hyperinsulinemia can promote breast cancer cell proliferation, migration and invasion. We found that these features were associated with increased expression of the mesenchymal markers vimentin and fibronectin, as well as increased uPA expression and activation through a mechanism mediated by ROS.

Many animals have adapted to the proximity of humans and thereby gained an advantage in a world increasingly affected by human activity. Numerous organisms have invaded novel areas and thereby increased their range. Here, we hypothesize that an ability to thrive in urban habitats is a key innovation that facilitates successful establishment and invasion. We test this hypothesis by relating the probability of establishment by birds on oceanic islands to the difference in breeding population density between urban and nearby rural habitats as a measure of urbanization in the ancestral range. This measure was the single-most important predictor of establishment success and the only statistically significant one, with additional effects of sexual dichromatism, number of releases and release effort, showing that the ability to cope with human proximity is a central component of successful establishment. Because most invasions occur as a consequence of human-assisted establishment, the ability to cope with human proximity will often be of central importance for successful establishment.

The purpose of this study is to investigate if the cholinergic stimulation by carbachol on tear secretion is a direct process or if it is also mediated by purinergic mechanisms. Experiments were performed in New Zealand male rabbits. The amount of tear secretion was measured with Schirmer's test and then analyzed by a HPLC protocol in order to study the nucleotide levels. Animal eyes were instilled with carbachol (a cholinergic agonist), pirenzepine, gallamine and 4-DAMP (muscarinic antagonists), PPADS, suramin and reactive blue 2 (purinergic antagonists), and a P2Y2 receptor small interfering RNA (siRNA). Tear secretion increased with the instillation of carbachol, approximately 84 % over control values 20 min after the instillation and so did Ap4A and ATP release. When we applied carbachol in the presence of muscarinic antagonists, tear volume only increased to 4 % with atropine, 12 % in the case of pirenzepine, 3 % with gallamine, and 8 % with 4-DAMP. In the presence of carbachol and purinergic antagonists, tear secretion was increased to 12 % (all values compared to basal tear secretion). By analyzing tear secretion induced with carbachol in presence of a P2Y2 receptor siRNA, we found that tear secretion was diminished to 60 %. The inhibition of tear secretion in the presence of carbachol and purinergic antagonists or P2Y2 siRNA occurred with no apparent change in the tear amount of Ap4A. These experiments demonstrated the participation of Ap4A in lacrimal secretion process.

Tumor necrosis factor alpha (TNF-?) is an important pro-inflammatory cytokine associated with a variety of ocular diseases. The currently available TNF-? inhibitors are etanercept, infliximab, adalimumab, golimumab, and certolizumab. Experimental and clinical studies on the intravitreal use of these agents have been reported with etanercept, infliximab, and adalimumab: etanercept has shown limited efficacy in scarce reports; infliximab has been associated with local safety concerns but appears to benefit certain cases; adalimumab has shown no efficacy in cases of age-related macular degeneration (AMD) or diabetic macular edema (DME), but the combination with bevacizumab may be effective in refractory cases of macular diseases. Further preclinical and clinical studies are warranted in order to be able to obtain a more robust conclusion on the use of intravitreal TNF-? inhibitors.

Organic agriculture and livestock farming is claimed to promote animal welfare and can offer animal products with better hygienic-sanitary quality, based on principles of health, ecology, fairness, and care. However, no clear advantages of organic milk (OM) versus conventional milk (CM) from tropical conditions are available. The aims of the study were to determine fatty acid profile, health-promoting (HPI) and thrombogenic (TI) indices, physicochemical composition, and somatic cell counts (SCC) of OM and CM in tropical south-eastern Mexico. Female cross-breed cows (400-600 kg) were employed. CM had larger values of saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) (63.6 %; 4.57 %) than OM (61.48 %; 4.22 %), while OM resulted in a larger value of monounsaturated fatty acid (MUFA) (34.3 %) than CM (31.7 %). HPI and TI showed that OM was more favorable than CM. Milk production and physicochemical composition (PC) as well as density had no significant difference, while SCC was significantly lower in OM than in CM on a monthly basis. These results showed that OM promotes a healthful and balanced diet, and is already produced by sustainable ecologic technologies employing traditional agrosilvopastoral management, which is more environmentally friendly and promotes ecological resilience.

Motor patterns driving rhythmic movements of our lower limbs during walking are generated by groups of neurons within the spinal cord, called central pattern generators (CPGs). After suffering a spinal cord injury (SCI), many descending fibers from our brain are severed or become nonfunctional, leaving the spinal CPG network without its initiating drive. Recent studies have focused on the importance of maintaining sensory stimulation to the limbs of SCI patients as a way to initiate and control the CPG locomotor network. We began assessing the role of sensory feedback to the locomotor CPG network using a neonatal mouse spinal cord preparation where the hindlimbs are still attached. Removing sensory feedback coming from the hindlimbs by way of a lower lumbar transection or by ventral root denervation revealed a positive correlation in the ability of sensory input deprivation to disrupt ongoing locomotor activity on older versus younger animals. The differences in the motor responses as a function of age could be correlated with the loss of excitatory activity from sensory afferents. Continued studies on this field could eventually provide key information that translates into the design of novel therapeutic strategies to treat patients who have suffered a SCI.

Studies on hexose consumption by Saccharomyces cerevisiae show that glucose is consumed faster than fructose when both are present (9:1 fructose to glucose) in the medium during the fermentation of Agave. The objective of this work was to select strains of S. cerevisiae that consume fructose equal to or faster than glucose at high fructose concentrations by analyzing the influence of different glucose concentrations on the fructose consumption rate. The optimal growth conditions were determined by a kinetics assay using high performance liquid chromatography (HPLC) using 50 g of glucose and 50 g of fructose per liter of synthetic medium containing peptone and yeast extract. Using the same substrate concentrations, strain ITD-00185 was shown to have a higher reaction rate for fructose over glucose. At 75 g of fructose and 25 g of glucose per liter, strain ITD-00185 had a productivity of 1.02 gL(-1) h(-1) after 40 h and a fructose rate constant of 0.071 h(-1). It was observed that glucose concentration positively influences fructose consumption when present in a 3:1 ratio of fructose to glucose. Therefore, adapted strains at high fructose concentrations could be used as an alternative to traditional fermentation processes.

The first paleoecological reconstruction of the biogeochemical conditions of the Gulf of Batabanó, Caribbean Sea was performed from (210)Pb-dated sediment cores. Depth profiles of 20 major elements and trace metals, organic compounds, grain size, and mollusk assemblage composition were determined from 9 stations encompassing unconsolidated sediments in the gulf. Spatial heterogeneity was evident for the geochemistry of sediments and for the mollusk assemblage composition. Our reconstruction indicates that pollution is not a critical threat to the ecosystem, although a slight historical increase of lead enrichment factor was detected probably due to long-range atmospheric fallout. Mollusk assemblages were composed by 168 species belonging to 59 families and no temporal trends in the species diversity or assemblage composition were detected, suggesting no depletion of diversity or habitat loss. Other signals of habitat loss such as changes in organic budget or increase of fine sediment fraction were absent or weak. Nitrogen retained in sediments changed by <1% in the century, indicating no historical events of eutrophication or oligotrophication in the gulf. Historical decrease of fine sediment fraction in the eastern sector would be linked to modifications in sedimentation rate, land use, and/or particle transport from the shelf border; this also suggests that both sectors have different sedimentary dynamics. Although, on theoretical grounds, historical fishery may have caused deleterious ecosystem effects by overexploitation of spiny lobster stocks, no evidence of habitat degradation or loss, caused by fisheries, could be detected.

Aluminum nanocontact conductance histograms are studied experimentally from room temperature up to near the bulk melting point. The dominant stable configurations for this metal show a very early crossover from shell structures at low wire diameters to ionic subshell structures at larger diameters. At these larger radii, the favorable structures are temperature-independent and consistent with those expected for ionic subshell (faceted) formations in face-centered cubic geometries. When approaching the bulk melting temperature, these local stability structures become less pronounced as shown by the vanishing conductance histogram peak structure.

Introduction: Vogt-Koyanagi-Harada (VKH) prognosis depends on early recognition and treatment; chronic disease may be developed when either delayed or inadequate treatment is performed, whereas other cases despite correct treatment are refractory to different drugs and also become chronic. We report a case of refractory VKH controlled with rituximab treatment., Case Report: A 41-year-old female with painful visual loss and headache was examined. (VA 0.4 in RE and hand movements (HM) in LE). Retinal examination demonstrated multiple serous retinal detachments in both eyes. High-dose oral steroids were started, followed by progressive tapering of prednisone. New acute anterior and posterior relapses were achieved, and other immunommodulators were progressively added-new high-dose steroid treatment, adalimumab, cyclosporine, and methotrexate-but patient had new anterior and posterior recurrences associated with tinnitus and headache. Thus, an infusion of 1 g of rituximab was administered after 15 months follow-up; the VA was 0.2 in RE and counting fingers in LE. Three additional doses of 1 g each were administered 1, 6, and 16 months later. We have achieved a final VA after 34 months follow-up of 0.2 in RE and HM in LE, with definitive control of inflammation, without acute relapses since rituximab was administered., Conclusion: After searching PubMed/Medline, this is the first report of VKH disease treated with rituximab. Additional studies are warranted to confirm the efficacy of this new approach for inflammatory control in refractory cases of VKH disease.

Purpose: To report a case of recurrent ocular inflammation after optimal therapy of bilateral syphilitic panuveitis responding to oral celecoxib., Methods: A case report was conducted., Results: A 76-year-old man presented with painful blurry vision in both eyes. Ocular examination disclosed bilateral panuveitis. Serological testing confirmed blood and cerebrospinal fluid syphilitic involvement. After 2 weeks of intravenous penicillin therapy, recurrent episodic sclerouveitis was observed., Conclusion: Ocular inflammation after healing of infectious uveitis is a rare ophthalmic sequela. In an immunocompetent patient, either re-infection or immune uveitis should be evoked. Non-steroidal therapeutic options, as celecoxib, could be a good option of treatment in such immune cases.

Background and Aims: An association between cardiovascular disease and osteoporosis is described. A number of drugs often used by patients with coronary heart disease, such as thiazides, statins and beta-blockers, have shown controversial effects on bone. 1) To study the possible association between coronary heart disease (CHD) and bone mass density (BMD), quantitative ultrasound measurements (QUS) and the prevalence of fragility and vertebral fractures. 2) To study the possible influence of a number of drugs, statins, thiazides and beta-blockers, on BMD and fractures., Methods: Case-control study performed on 74 postmenopausal women who had recently suffered from CHD, and 111 age-matched controls. BMD was measured by Dual X-Ray Absorptiometry (DXA) at the lumbar spine and proximal femur. Quantitative Ultrasound (QUS) was also measured at the heel. Vertebral fractures were diagnosed by lateral, thoracic and lumbar X-rays. The occurrence of non-vertebral fractures was determined by examination of medical records., Results: Patients with CHD had higher values of BMI. They had a higher prevalence of arterial hypertension and hyperlipidemia, and consequently higher consumption of beta-blockers and statins, but not of thiazides, and had lower alcohol consumption. Patients with CHD had higher BMD values, measured by DXA at the proximal femur, than controls, but there were no differences in DXA values at the lumbar spine or QUS at the heel between the two groups. The prevalence of all fragility factures was slightly higher in patients with CHD, but not to a significant extent. The prevalence of vertebral fractures was similar in the two groups. In a logistic analysis to identify factors associated with all fractures, beta-blockers were positively associated with fragility fractures, and DXA at the femoral neck was inversely associated with fragility fractures., Conclusions: Postmenopausal women with CHD have higher values of BMD at the proximal femur but, despite this, show a slight but non-significant increase in the prevalence of fragility fractures. Beta-blockers are independently associated with fragility fractures, but thiazides and statins are not.