Evaluation of the Aquatic Toxicity of Several Triazole Fungicides.

Fungicides play an important role in crop protection, but they have also been shown to adversely affect non-target organisms, including those living in the aquatic environment. The aim of the present study is to combine experimental and computational approaches to evaluate the effects of flutriafol, metconazole, myclobutanil, tebuconazole, tetraconazole and triticonazole on aquatic model organisms and to obtain information on the effects of these fungicides on Lemna minor, a freshwater plant, at the molecular level. The EC50 (the half-maximum effective concentration) values for the growth inhibition of Lemna minor in the presence of the investigated fungicides show that metconazole (EC50 = 0.132 mg/L) and tetraconazole (EC50 = 0.539 mg/L) are highly toxic, tebuconazole (EC50 = 1.552 mg/L), flutriafol (EC50 = 3.428 mg/L) and myclobutanil (EC50 = 9.134 mg/L) are moderately toxic, and triticonazole (EC50 = 11.631 mg/L) is slightly toxic to this plant. The results obtained with the computational tools TEST, ADMETLab2.0 and admetSAR2.0 also show that metconazole and tetraconazole are toxic to other aquatic organisms: Pimephales promelas, Daphnia magna and Tetrahymena pyriformis. A molecular docking study shows that triazole fungicides can affect photosynthesis in Lemna minor because they strongly bind to C43 (binding energies between -7.44 kcal/mol and -7.99 kcal/mol) and C47 proteins (binding energies between -7.44 kcal/mol and -8.28 kcal/mol) in the reaction center of photosystem II, inhibiting the binding of chlorophyll a to these enzymes. In addition, they can also inhibit glutathione S-transferase, an enzyme involved in the cellular detoxification of Lemna minor.

Awakening adult neural stem cells: NOX signalling as a positive regulator of the quiescence-to-proliferation transition in the Xenopus retina.

A growing wealth of data suggest that reactive oxygen species (ROS) signalling might be crucial in conferring embryonic or adult stem cells their specific properties. However, how stem cells control ROS production and scavenging, and how ROS in turn contribute to stemness, remain poorly understood. Using the Xenopus retina as a model system, we first investigated the redox status of retinal stem cells (RSCs). We discovered that they exhibit higher ROS levels compared with progenitors and retinal neurons, and express a set of specific redox genes. We next addressed the question of ROS functional involvement in these cells. Using pharmacological or genetic tools, we demonstrate that inhibition of NADPH oxidase-dependent ROS production increases the proportion of quiescent RSCs. Surprisingly, this is accompanied by an apparent acceleration of the mean division speed within the remaining proliferating pool. Our data further unveil that such impact on RSC cell cycling is achieved by modulation of the Wnt/Hedgehog signalling balance. Altogether, we highlight that RSCs exhibit distinctive redox characteristics and exploit NADPH oxidase signalling to limit quiescence and fine-tune their proliferation rate.

Enfoque de género en la gestión local del riesgo de desastres en Costa Rica desde una mirada interseccional / Gender approach in local disaster risk management in Costa Rica from an intersectional perspective

Resumen Los gobiernos municipales de Costa Rica tienen un papel significativo en el Sistema Nacional de Gestión del Riesgo (SNGR) para enfrentar las múltiples amenazas y riesgos que afectan al país desde sus territorios. Los distintos marcos y políticas que trabajan en el enfoque de la Gestión del Riesgo de Desastres (GRD) promueven la realización de análisis de riesgos como proceso que contribuye a su reducción y mitigación, y destacan el enfoque de género como principio o eje para visibilizar la necesidad de realizar revisiones y acciones diferenciadas por género. El presente artículo recoge la investigación realizada que responde a la pregunta "¿Cuáles son los elementos psicosociales que influyen en la puesta en práctica de la transversalización del enfoque de género en los procesos de la GRD de las oficinas municipales?" Esta pregunta se respondió desde la Psicología Social Comunitaria y la Psicología Social Feminista. Se realizó un estudio con enfoque cualitativo y diseño fenomenológico, en el que se aplicaron entrevistas a representantes institucionales en GRD y género. Se identificaron doce elementos psicosociales que influyen en la transversalización del enfoque de género en la GRD municipal, que deben visibilizarse y pueden ser trabajados para abordar los riesgos de dos poblaciones históricamente discriminadas: mujeres y población LGTBIQ+. Trabajar las desigualdades de género como causa subyacente del riesgo es prioritario para la GRD.

Abstract The city governments of Costa Rica have a significant role in the National Risk Management System (SNGR in Spanish) to face the multiple threats and risks that affect the country from their territories. The different frameworks and policies that work with the Disaster Risk Management approach, among which are international (e. g., Sendai Framework for Action), regional (e. g., Central American Policy for Comprehensive Disaster Risk Management), and national instruments (e. g., National Risk Management Policy), promote risk analysis as a process that contributes to their reduction and mitigation, which, together with specific policies focused on gender (e. g., Convention on the Elimination of All Forms of Discrimination Against Women [CEDAW]), highlight the gender approach as a principle or axis, making the need to carry out reviews and actions differentiated by gender visible. The growth of inequalities in events such as disasters emphasizes the fact that there are gender differences in the perception of risks, the levels of vulnerability that exist and the capacities to cope. This article collects the research carried out that answers the question: "What are the psychosocial elements that influence the implementation of mainstreaming the gender approach in DRM processes in municipal offices?" from Community Social Psychology and Feminist Social Psychology. A study with a qualitative approach and phenomenological design was carried out, in which interviews were applied to institutional representatives in DRM and gender. The first seeks to promote processes of social transformation, considering the psychosocial processes that permeate community dynamics, which, in turn, are influenced by specific contexts. As for Feminist Psychology, it promotes the identification of inequalities and the creation of options for change. The relationship between feminist political perspectives and psychological practices and sexual and gender differences were considered as causes of inequalities, generating certain psychosocial analyzes not widely developed so far. A subjective perspective to the lived experience of the people participating in the research was considered in order to emphasize the meanings and knowledge as a process, based on interviews with institutional representatives of municipal offices and national institutions both focused on DRM or gender. Twelve psychosocial elements that influence the mainstreaming of the gender approach in municipal DRM were identified: the need for training and awareness, the requirement of political will, the naturalization of gender roles and stereotypes, the recognition of gender differences, resistance to mainstreaming gender, subjectivity, the presence or absence of inter and intra-institutional articulations, the social participation of women, the recognition of gender violence, the recognition of vulnerable populations, the cultural context and social inequalities. Moreover, gender inequalities are recognized as an element that affects and emphasizes the vulnerabilities of specific populations, such as women of different ages, transgender people, people with disabilities, among others. The research allowed an approach to ten different territorial contexts where DRM is put into practice from an office or as a process, and how the experience of the people who lead them understands the gender approach, contrasting with the institutional perspective applied at the national level. It is concluded that these should be made visible and can be worked on to address the risks of two historically discriminated populations: women and LGTBIQ+ population. Considering gender inequalities as an underlying cause of risk is a priority for Disaster Risk Management.

Inclusion complex of ketoconazole and p-sulfonic acid calix[6]arene improves antileishmanial activity and selectivity against Leishmania amazonensis and Leishmania infantum.

Many previous studies presented the effectiveness of ketoconazole (KTZ) against leishmaniasis. However, the bioavailability and therapeutic efficacy of free KTZ are limited due to its low aqueous solubility. In this study, an inclusion complex (IC6HKTZ) was prepared with p-sulfonic acid calix[6]arene (CX6SO3H) to improve the solubility and efficacy of KTZ against Leishmania amazonensis and Leishmania infantum promastigotes. A linear increase in KTZ solubility as a function of CX6SO3H concentration was verified using the phase-solubility diagram. The resulting diagram was classified as AL-type and a 1:1 host-guest stoichiometry was assumed to prepare IC6HKTZ by freeze-drying. FTIR, TG/DSC, XRD, and solid-state 13C NMR spectroscopy analyses were performed to confirm the formation of IC6HKTZ. The solubility enhancement of KTZ by 120.00 µM CX6SO3H was about 95 times. The IC50 values of IC6HKTZ and free KTZ were 3.95 and 14.35 µM for Leishmania amazonensis and 6.74 and 17.47 µM for Leishmania infantum, respectively. The viability of DH82 macrophages was not affected by CX6SO3H. These results show that CX6SO3H is a new supramolecular carrier system that improves antileishmanial activities to KTZ for the treatment of cutaneous and visceral leishmaniasis.

Deep magma storage during the 2021 La Palma eruption.

The 2021 La Palma eruption provided an unpreceded opportunity to test the relationship between earthquake hypocenters and the location of magma reservoirs. We performed density measurements on CO2-rich fluid inclusions (FIs) hosted in olivine crystals that are highly sensitive to pressure via calibrated Raman spectroscopy. This technique can revolutionize our knowledge of magma storage and transport during an ongoing eruption, given that it can produce precise magma storage depth constraints in near real time with minimal sample preparation. Our FIs have CO2 recorded densities from 0.73 to 0.98 g/cm3, translating into depths of 15 to 27 km, which falls within the reported deep seismic zone recording the main melt storage reservoir.

Assessment of the Effects of Triticonazole on Soil and Human Health.

Triticonazole is a fungicide used to control diseases in numerous plants. The commercial product is a racemate containing (R)- and (S)-triticonazole and its residues have been found in vegetables, fruits, and drinking water. This study considered the effects of triticonazole on soil microorganisms and enzymes and human health by taking into account the enantiomeric structure when applicable. An experimental method was applied for assessing the effects of triticonazole on soil microorganisms and enzymes, and the effects of the stereoisomers on soil enzymes and human health were assessed using a computational approach. There were decreases in dehydrogenase and phosphatase activities and an increase in urease activity when barley and wheat seeds treated with various doses of triticonazole were sown in chernozem soil. At least 21 days were necessary for the enzymes to recover the activities. This was consistent with the diminution of the total number of soil microorganisms in the 14 days after sowing. Both stereoisomers were able to bind to human plasma proteins and were potentially inhibitors of human cytochromes, revealing cardiotoxicity and low endocrine disruption potential. As distinct effects, (R)-TTZ caused skin sensitization, carcinogenicity, and respiratory toxicity. There were no significant differences in the interaction energies of the stereoisomers and soil enzymes, but (S)-TTZ exposed higher interaction energies with plasma proteins and human cytochromes.

A Cheminformatics Study Regarding the Human Health Risks Assessment of the Stereoisomers of Difenoconazole.

Difenoconazole is a chemical entity containing two chiral centers and having four stereoisomers: (2R,4R)-, (2R,4S)-, (2S,4R)- and (2S,4S)-difenoconazole, the marketed product containing a mixture of these isomers. Residues of difenoconazole have been identified in many agricultural products and drinking water. A computational approach has been used to evaluate the toxicological effects of the difenoconazole stereoisomers on humans. It integrates predictions of absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles, prediction of metabolism sites, and assessment of the interactions of the difenoconazole stereoisomers with human cytochromes, nuclear receptors and plasma proteins by molecular docking. Several toxicological effects have been identified for all the difenoconazole stereoisomers: high plasma protein binding, inhibition of cytochromes, possible hepatotoxicity, neurotoxicity, mutagenicity, skin sensitization potential, moderate potential to produce endocrine disrupting effects. There were small differences in the predicted probabilities of producing various biological effects between the distinct stereoisomers of difenoconazole. Furthermore, there were significant differences between the interacting energies of the difenoconazole stereoisomers with plasma proteins and human cytochromes, the spectra of the hydrogen bonds and aromatic donor-acceptor interactions being quite distinct. Some distinguishing results have been obtained for the (2S,4S)-difenoconazole: it registered the highest value for clearance, exposed reasonable probabilities to produce cardiotoxicity and carcinogenicity and negatively affected numerous nuclear receptors.

Magmatic water content controls the pre-eruptive depth of arc magmas.

Vanguard efforts in forecasting volcanic eruptions are turning to physics-based models, which require quantitative estimates of magma conditions during pre-eruptive storage. Below active arc volcanoes, observed magma storage depths vary widely (~0 to 20 kilometers) and are commonly assumed to represent levels of neutral buoyancy. Here we show that geophysically observed magma depths (6 ± 3 kilometers) are greater than depths of neutral buoyancy, ruling out this commonly assumed control. Observed depths are instead consistent with predicted depths of water degassing. Intrinsically wetter magmas degas water and crystallize deeper than dry magmas, resulting in viscosity increases that lead to deeper stalling of ascending magma. The water-depth relationship provides a critical constraint for forecasting models by connecting depth of eruption initiation to its volatile fuel.

Rheumatoid arthritis-related interstitial lung disease (RA-ILD): a possible association between disease activity and prognosis.

OBJECTIVES: We hypothesized that RA disease activity might be associated with the survival of RA-ILD patients. To evaluate this possibility, we analyzed data on disease activity during follow-up in an RA-ILD cohort and compared disease activity between surviving patients and those who died during follow-up. METHODS: RA-ILD patients referred for medical evaluation and treatment at a single center, with CDAI scores during all follow up were included. We estimated the HR of the mean of the CDAI score during follow-up with survival. Also, we compared the survival function of patients with high disease activity (CDAI scores ≥ 22) during all follow-up with those with moderate and low disease activity. RESULTS: Thirty-seven patients were included. The mean of the CDAI score during follow-up was higher in death patients (median 30.8 ± 18.5 Vs. 16.8 ± 11.3), and a single unit increase in the mean of the CDAI score was associated with non-survival, HR:1.07 (95% CI: 1.02 -1.12). Patients with high disease activity during all follow-up (CDAI scores > 22) had lower survival function in comparison with moderate and low disease activity (P = 0.042). CONCLUSION: The results of the study suggest that higher RA disease activity is associated with a worse prognosis of RA-ILD patients. The hypothesis that high disease activity is associated with worse survival in RA-ILD patients must be evaluated in more extensive cohort studies and clinical trials. KEY POINTS: • RA-ILD patients with high disease activity during follow-up had a worse prognosis than those with moderate or low disease activity. • The study results suggest the hypothesis that patients with RA-ILD must be treated with a treat to target strategy, with the aim of remission or low RA disease activity.

Advanced Composites Based on Sea Buckthorn Carotenoids for Mayonnaise Enrichment.

This study aimed at the extraction and encapsulation of the carotenoids from sea buckthorn fruits and obtaining value-added mayonnaise. First, the carotenoids from sea buckthorn fruits were extracted using ultrasound-assisted extraction. Then, they were microencapsulated through complex coacervation and freeze-drying techniques using different wall material combinations. Two powders were obtained and analyzed in terms of encapsulation efficiency, total carotenoid content, antioxidant activity, stability of phytochemicals and color, morphological structure, and in vitro digestibility. All results pointed out that the carotenoid molecules were successfully encapsulated within the mixture of alginate, agar, and chitosan, with a 61.17 ± 0.89% encapsulation efficiency. To probe the functionality, the powder was added into mayonnaise in 2.5% and 5% amounts. The obtained mayonnaise samples were characterized in terms of phytochemical and antioxidant activity properties with their storage stability and texture, color, and sensory characteristics. A significant increase of total carotenoid content and antioxidant activity compared to the control sample was observed. The addition of powder also led to improved texture by increasing the firmness and adhesion. In addition, the sensory evaluation indicated an improved color and overall acceptability of the value-added mayonnaise. Thus, sea buckthorn extracts may be considered as valuable ingredients for the development of added-value food products.

Fast pyrolysis as a tool for obtaining levoglucosan after pretreatment of biomass with niobium catalysts.

Levoglucosan (LGA) is a promising chemical platform derived from the pyrolysis of biomass that offers access to a variety of value-added products. We report an efficient route to produce LGA via the pretreatment of biomass with niobium compounds (oxalate, chloride and oxide) followed by fast pyrolysis coupled with gas chromatography-mass spectrometry (Py-GC-MS) at temperatures of 350-600 °C. Catalytic pretreatment reduces the quantity of lignin in the biomass, concentrates the cellulose and enhance LGA formation during fast pyrolysis. The pretreatment also removes alkaline metals, preventing competitive side reactions. The effect of several parameters such as catalyst weight, time, temperature, and solvent, with the optimal pretreatment conditions determined to be 3 (wt.%) niobium oxalate for 1 h at 23 °C in water. Pretreatment increased the LGA yields by 6.40-fold for sugarcane bagasse, 4.15-fold for elephant grass, 4.13-fold for rice husk, 2.86-fold for coffee husk, and 1.86-fold for coconut husk as compared to the raw biomasses. These results indicate that biomass pretreatment using niobium derivates prior fast pyrolysis can be a promising technique for biomass thermochemical conversion in LGA and others important pyrolytic products.

Computational Assessment of Chito-Oligosaccharides Interactions with Plasma Proteins.

It is widely recognized that chitin and chitosan are potential sources of bioactive materials and that their oligosaccharides reveal various biological activities (including antimicrobial) that are correlated with their structures and physicochemical properties. This study uses the molecular docking approach to assess the interactions of small chito-oligosaccharides (MW< 1500 Da) with plasma proteins in order to obtain information regarding their fate of distribution in the human organism. There are favorable interactions of small chito-oligomers with plasma proteins, the interactions with human serum albumin being stronger than those with α-1-acid glycoprotein. The interaction energies increase with increasing the molecular weight, decrease with increasing deacetylation degrees and are reliant on the deacetylation pattern. This study could inform the application of chito-oligosaccharides with varying molecular weights, degrees, and patterns of deacetylation in human health.

In silico Assessment of Pharmacological Profile of Low Molecular Weight Oligo-Hydroxyalkanoates.

Polyhydroxyalkanoates (PHAs) are a large class of polyesters that are biosynthesized by microorganisms at large molecular weights (Mw > 80 kDa) and have a great potential for medical applications because of their recognized biocompatibility. Among PHAs, poly(3-hydroxybutyrate), poly(4-hydroxybutyrate), poly(3-hydroxyvalerate), poly(4-hydroxyvalerate), and their copolymers are proposed to be used in biomedicine, but only poly(4-hydroxybutyrate) has been certified for medical application. Along with the hydrolysis of these polymers, low molecular weight oligomers are released typically. In this study, we have used a computational approach to assess the absorption, distribution, metabolism, and excretion (ADME)-Tox profiles of low molecular weight oligomers (≤32 units) consisting of 3-hydroxybutyrate, 4-hydroxybutyrate, 3-hydroxyvalerate, 4-hydroxyvalerate, 3-hydroxybutyrate-co-3-hydroxyvalerate, and the hypothetical PHA consisting of 4-hydroxybutyrate-co-4-hydroxyvalerate. According to our simulations, these oligomers do not show cardiotoxicity, hepatotoxicity, carcinogenicity or mutagenicity, and are neither substrates nor inhibitors of the cytochromes involved in the xenobiotic's metabolism. They also do not affect the human organic cation transporter 2 (OCT2). However, they are considered to be inhibitors of the organic anion transporters OATP1B1, and OATP1B3. In addition, they may produce eye irritation, and corrosion, skin irritation and have a low antagonistic effect on the androgen receptor.

Plasmodium falciparum sexual parasites regulate infected erythrocyte permeability.

To ensure the transport of nutrients necessary for their survival, Plasmodium falciparum parasites increase erythrocyte permeability to diverse solutes. These new permeation pathways (NPPs) have been extensively characterized in the pathogenic asexual parasite stages, however the existence of NPPs has never been investigated in gametocytes, the sexual stages responsible for transmission to mosquitoes. Here, we show that NPPs are still active in erythrocytes infected with immature gametocytes and that this activity declines along gametocyte maturation. Our results indicate that NPPs are regulated by cyclic AMP (cAMP) signaling cascade, and that the decrease in cAMP levels in mature stages results in a slowdown of NPP activity. We also show that NPPs facilitate the uptake of artemisinin derivatives and that phosphodiesterase (PDE) inhibitors can reactivate NPPs and increase drug uptake in mature gametocytes. These processes are predicted to play a key role in P. falciparum gametocyte biology and susceptibility to antimalarials.

Breastfeeding practices and complementary feeding in Ecuador: implications for localized policy applications and promotion of breastfeeding: a pooled analysis.

BACKGROUND: Best practices in breastfeeding are often not followed despite appropriate levels of knowledge and positive attitudes regarding the benefits of human milk. For many reasons, some women do not initiate breastfeeding, suspend breastfeeding early, or initiate complementary feeding earlier than recommended. Usual measurement methods use large sample surveys at a national scale, which are not well suited for monitoring sub-national differences. METHODS: In order to understand how local infant feeding practices could influence policy and promotion practices, we apply data pooling methodology to analyse breastfeeding patterns in different Ecuadorian settings: Cumbayá parish, located near Quito, the Ecuadorian capital; the city of Macas and rural surroundings in the Amazon basin province of Morona Santiago; and the province of Galapagos. Surveys were conducted independently between August 2017 and August 2018; while they are representative of each respective setting, sampling designs and survey methods differ, but the same demographic information and data based on standard breastfeeding indicators established by the World Health Organization (WHO) were collected. In order to account for differences in the different settings, the design effect of each survey was considered in the analysis. RESULTS: Significant differences were found in breastfeeding practices between the suburban Cumbayá parish near Quito and Galapagos on one hand, and urban and rural parts of Morona Santiago, on the other. The rates of early breastfeeding initiation and age-appropriate breastfeeding are significantly higher in urban and rural Morona Santiago then in Cumbayá or Galapagos, while the rate of exclusive breastfeeding is highest in rural parts of Morona Santiago. No significant differences were found in complementary feeding practices between Cumbayá and Galapagos, but there are with urban and rural Morona Santiago. Initiation of breastfeeding in the first hour after birth occurs in only 36.2% of cases in Cumbayá but in 75.4% of cases in urban Morona. CONCLUSIONS: Differences among regions reflect specific opportunities and barriers to practices related to promoting optimal infant health and nutrition. Consequently, regional or local conditions that often are not apparent in national-level data should orient policies and promotion activities in specific populations.

Deeper inside the specificity of lysozyme when degrading chitosan. A structural bioinformatics study.

Lysozymes that were used in numerous in vitro experiments of chitosan degradation were regularly from hen egg-white. Human lysozyme has been proved to be more active than hen egg-white lysozyme when exerting its bacteriostatic effect and there is possible that the two enzymes have some different structural properties. Consequently, within this study, we compared the structural and physicochemical properties of the human and egg-white lysozymes and used the molecular docking approach to obtain information concerning the specificity of the interactions between chitooligosaccharides with these enzymes. There is 60.47% of identity between the sequences of the human and the hen egg-white lysozymes, but the amino acids that are involved in the interactions of considered lysozymes with N-acetylchitohexaose are well conserved. Superimposition of the structures of investigated lysozymes reveals their structural similarity, the RMSD value being 1.198 Å for 118 equivalent carbon alpha atom pairs from a total of 129. There are some local physicochemical properties like the distribution of the electrostatic potential and the hydrophobicity of the catalytic cavities of the enzyme that are quite different. Substrate specificities of human and hen egg-white lysozyme with respect to chito-oligosaccharides are not clearly distinguishable but they are dependent on the molecular weight, deacetylation degree and pattern of deacetylation.

Fossils from Mille-Logya, Afar, Ethiopia, elucidate the link between Pliocene environmental changes and Homo origins.

Several hypotheses posit a link between the origin of Homo and climatic and environmental shifts between 3 and 2.5 Ma. Here we report on new results that shed light on the interplay between tectonics, basin migration and faunal change on the one hand and the fate of Australopithecus afarensis and the evolution of Homo on the other. Fieldwork at the new Mille-Logya site in the Afar, Ethiopia, dated to between 2.914 and 2.443 Ma, provides geological evidence for the northeast migration of the Hadar Basin, extending the record of this lacustrine basin to Mille-Logya. We have identified three new fossiliferous units, suggesting in situ faunal change within this interval. While the fauna in the older unit is comparable to that at Hadar and Dikika, the younger units contain species that indicate more open conditions along with remains of Homo. This suggests that Homo either emerged from Australopithecus during this interval or dispersed into the region as part of a fauna adapted to more open habitats.

Aseismic mid-crustal magma reservoir at Cleveland Volcano imaged through novel receiver function analyses.

Processes related to eruptions at arc volcanoes are linked by structures that transect the entire crust. Imaging the mid- to lower-crustal portions (here, ~5-15 km and >15 km respectively) of these magmatic systems where intermediate storage may occur has been a longstanding challenge. Tomography, local seismic source studies, geodetic, and geochemical constraints, are typically most sensitive to shallow (<5 km) storage and/or have insufficient resolution at these depths. Geophysical methods are even further limited at frequently-erupting volcanoes where well-developed trans-crustal magmatic systems are likely to exist, due to a lack of deep seismicity. Here we show direct evidence for mid-crustal magma storage beneath the frequently erupting Cleveland volcano, Alaska, using a novel application of seismic receiver functions. We use P-s scattered waves from the Moho as virtual sources to investigate S-wave velocities between the Moho and the surface. Our forward modeling approach allows us to provide direct constraints on the geometry of low velocity regions beneath volcanoes despite having a comparatively sparse seismic network. Our results show clear evidence of mid-crustal magma storage beneath the depths of located volcanic seismicity. Future work using similar approaches will enable an unprecedented comparative examination of magmatic systems beneath sparsely instrumented volcanoes globally.

Solubility and ADMET profiles of short oligomers of lactic acid.

Polylactic acid (PLA) is a polymer with an increased potential to be used in different medical applications, including tissue engineering and drug-carries. The use of PLA in medical applications implies the evaluation of the human organism's response to the polymer inserting and to its degradation products. Consequently, within this study, we have investigated the solubility and ADMET profiles of the short oligomers (having the molecular weight lower than 3000 Da) resulting in degradation products of PLA. There is a linear decrease of the molar solubility of investigated oligomers with molecular weight. The results that are obtained also reveal that short oligomers of PLA have promising pharmacological profiles and limited toxicological effects on humans. These oligomers are predicted as potential inhibitors of the organic anion transporting peptides OATP1B1 and OATP1B3, they present minor probability to affect the androgen and glucocorticoid receptors, have a weak potential of hepatotoxicity, and may produce eye injuries. These outcomes may be used to guide or to supplement in vitro and/or in vivo toxicity tests such as to enhance the biodegradation properties of the biopolymer.

Evolution of Pulmonary Function in a Cohort of Patients with Interstitial Lung Disease and Positive for Antisynthetase Antibodies.

OBJECTIVE: To describe the evolution of the pulmonary function in patients with interstitial lung disease (ILD) who are positive for at least 1 of the antisynthetase antibodies (ASAB) after medical treatment, and to compare whether the evolution of pulmonary function is associated with the type of ASAB. METHODS: Patients with ILD and positive for at least 1 of the ASAB (anti-Jo1, anti-PL7, anti-PL12, anti-EJ, or anti-OJ) were included. The clinical evolution, time until death or censoring, and improvement of lung disease were registered. RESULTS: The study included 118 patients. Most of the patients had a high extent of ground glass opacities in high-resolution computed tomography (HRCT) and low extent of fibrosis. In the final evaluation of pulmonary function (median 749.5 days of followup), 67% of the patients had lung disease improvement. The improvement occurred within the first 6 months after initiating medical treatment; thereafter, pulmonary function remained stable in most of the patients. A decrease of the extent of ground glass opacities was demonstrated in HRCT at followup in those patients with pulmonary improvement. No differences were observed in the percentage of patients who achieved improvement between the ASAB groups, or in survival. CONCLUSION: Improvement of pulmonary function was observed in 67% of the patients. Improvement was observed in all ASAB groups and occurred within 6 months after initiating medical treatment.