Crystal structure and Hirshfeld surface analysis of 5-hy-droxy-penta-nehydrazide.

Carb-oxy-hydrazides are widely used in medicinal chemistry because of their medicinal properties and many drugs have been developed containing this functional group. A suitable inter-mediate to obtain potential hydrazide drug candidates is the title compound 5-hy-droxy-penta-nehydrazide, C5H12N2O2 (1). The aliphatic compound can react both via the hydroxyl and hydrazide moieties forming derivatives, which can inhibit Mycobacterium tuberculosis catalase-peroxidase (KatG) and consequently causes death of the pathogen. In this work, the hydrazide was obtained via a reaction of a lactone with hydrazine hydrate. The colourless prismatic single crystals belong to the ortho-rhom-bic space group Pca21. Regarding supra-molecular inter-actions, the compound shows classic medium to strong inter-molecular hydrogen bonds involving the hydroxyl and hydrazide groups. Besides, the three-dimensional packing also shows weak H⋯H and C⋯H contacts, as investigated by Hirshfeld surface analysis (HS) and fingerprint plots (FP).

Enhancement of Arthrospira sp. culturing for sulfate removal and mining wastewater bioremediation.

Sulfate content in mining wastewater can reach concentrations over 2,000 mg·L-1, which is considered as a pollutant of concern. In this article, two cyanobacteria species were cultured using highly sulfated wastewater (3,000 mg·L-1) as the culture medium. This investigation aimed to analyze the sulfate bioremediation potential of microalgae while enhancing the uptaking of this pollutant through the design of a novel nutritional medium. The results obtained show the suitability of Arthrospira maxima as a bioremediation organism of sulfated wastewater. The appropriateness of this organism is based on its great growth performance when cultured in this residue, 2.16 times higher than the initial value. Moreover, the initially obtained sulfate reduction, 23.3%, was significantly enhanced to a final removal of 73% (2,247 mg·L-1). In addition, scanning electron microscopy and energy-dispersive X-ray spectroscopy were used to evaluate sulfur crystallization. To the best of our knowledge, there are no previous works focused on microalgal sulfate removal that have reached such an uptaking rate. Accordingly, this study presents the highest performance on sulfate microalgal bioremediation published to date. Our findings suggest that A. maxima can be cultured for sulfated wastewater bioremediation while showing a removal yield that is theoretically sufficient for industrial applications.

To the best of our knowledge, this is the first study focused on the bioremediation potential of Arthrospira genre (Spirulin) for highly sulfated wastewaters depuration. Moreover, according to the available data, our study achieved the highest sulfate removal rate by using microalgae as a bioremediation organism. Thus, we strongly believe that our investigation provides up-to-date data in terms of mining wastewaters bioremediation, which can cause a strong impact on how these residues are managed.

Variación morfológica del neurocráneo de ocho especies de batoideos (Chondrichtyes) / Morphological variation of the neurocranium of eight species of batoids (Chondrichthyes)

RESUMEN: Los estudios sobre sistemática y anatomía han revelado que las características del esqueleto de los batoideos muestran gran variabilidad y proporcionan información importante sobre las relaciones de parentesco de este grupo, es por ello que el objetivo de este trabajo fue describir la morfología del neurocráneo de ocho especies de batoideos. Los batoideos estudiados mostraron grandes variaciones principalmente en el rostrum, número de fontanelas, orientación de las cápsulas nasales y en la condición y desarrollo de los procesos pre y postorbitales. Las variaciones presentes en las especies estudiadas nos permitieron agrupar a los cráneos en tres morfotipos. El primero incluye a Narcine bancroftii; este morfotipo presenta características únicas, como son un rostrum cuadrado y cartílagos anterorbitarios ramificados; no presentan procesos preorbitales y postorbitales, cresta supraorbital ni apéndice rostral. El segundo morfotipo está formado por Rostroraja texana y Pseudobatus lentiginosus, los cuales tienen un rostrum bien desarrollado con un apéndice rostral en la región anterior, dos fontanelas, arcos yugales en la región occipital y procesos preorbitales y postorbitales poco desarrollados. El tercer morfotipo incluye a las especies de miliobatoideos los cuales tienen un rostrum reducido o ausente, un apéndice rostral separado del cráneo, con una fontanela y procesos preorbitales y postobitales desarrollados. La mayoría de las especies presentan variaciones morfológicas a lo largo de su desarrollo, por lo que al llevar a cabo estudios filogenéticos es importante utilizar caracteres de organismos adultos.

SUMMARY: Systematics and anatomy studies have revealed that characteristics of the batoids skeleton show significant variability and provide relevant information on the phylogenetic relationships of this group. Within this framework, our objective is describing the neurocranium morphology in eight species of batoids. Large variations were found, mainly in the rostrum, number of fontanelles, orientation of nasal capsules, and the condition and development of the pre- and post-orbital processes. These variations allowed us to group these craniums in three morphotypes. The first, including Narcine bancroftii, has unique characteristics, such as a squared rostrum and branched anterorbital cartilages; there are no pre-or post- orbital processes, supraorbital crest or rostral appendix. The second morphotype includes Rostroraja texana and Pseudobatus lentiginosus, which have a well-developed rostrum with a rostral appendix in the anterior region, two fontanelles, jugal arches in the occipital region, and pre- and post-orbital processes poorly developed. The third morphotype includes myliobatoids species, which have small or absent rostrum, rostral appendix separated from the cranium, one fontanelle, and developed pre- and post-orbital processes. Most species have morphological variations throughout their development; therefore, when conducting phylogenetic studies, using characters from adult specimens is fundamental.

A nearby transiting rocky exoplanet that is suitable for atmospheric investigation.

Spectroscopy of transiting exoplanets can be used to investigate their atmospheric properties and habitability. Combining radial velocity (RV) and transit data provides additional information on exoplanet physical properties. We detect a transiting rocky planet with an orbital period of 1.467 days around the nearby red dwarf star Gliese 486. The planet Gliese 486 b is 2.81 Earth masses and 1.31 Earth radii, with uncertainties of 5%, as determined from RV data and photometric light curves. The host star is at a distance of ~8.1 parsecs, has a J-band magnitude of ~7.2, and is observable from both hemispheres of Earth. On the basis of these properties and the planet's short orbital period and high equilibrium temperature, we show that this terrestrial planet is suitable for emission and transit spectroscopy.

High-Resolution Magic Angle Spinning (HR-MAS) NMR-Based Fingerprints Determination in the Medicinal Plant Berberis laurina.

Berberis laurina (Berberidaceae) is a well-known medicinal plant used in traditional medicine since ancient times; however, it is scarcely studied to a large-scale fingerprint. This work presents a broad-range fingerprints determination through high-resolution magical angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy, a well-established flexible analytical method and one of most powerful "omics" platforms. It had been intended to describe a large range of chemical compositions in all plant parts. Beyond that, HR-MAS NMR allowed the direct investigation of botanical material (leaves, stems, and roots) in their natural, unaltered states, preventing molecular changes. The study revealed 17 metabolites, including caffeic acid, and berberine, a remarkable alkaloid from the genus Berberis L. The metabolic pattern changes of the leaves in the course of time were found to be seasonally dependent, probably due to the variability of seasonal and environmental trends. This metabolites overview is of great importance in understanding plant (bio)chemistry and mediating plant survival and is influenceable by interacting environmental means. Moreover, the study will be helpful in medicinal purposes, health sciences, crop evaluations, and genetic and biotechnological research.

Supramolecular polyelectrolyte complexes based on cyclodextrin-grafted chitosan and carrageenan for controlled drug release.

In the present study, supramolecular polyelectrolyte complexes (SPEC) based on a cyclodextrin-grafted chitosan derivative and carrageenan were prepared and evaluated for controlled drug release. Samples were characterized by FTIR, SEM, and ζ-potential measurements, which confirmed the formation of the polymeric complex. The phenolphthalein test confirmed the presence and availability of inclusion sites from the attached ßCD. Silver sulfadiazine was used as the model drug and the association with the SPEC was studied by FTIR and computational molecular modeling, using a semi-empirical method. DRS and TEM analyses have shown that Ag+ ions from the drug were reduced to form metallic silver nanostructures. In vitro tests have shown a clear bacterial activity toward Gram-positive bacteria Staphylococcus aureus and Enterococcus durans/hirae and Gram-negative bacteria Klebsiella pneumoniae and Escherichia coli. Finally, this work shows that ßCD-chitosan/carrageenan supramolecular polyelectrolyte complexes hold an expressive potential to be applied as a polymer-based system for controlled drug release.

Evaluation of a workshop to teach a new surgical technique in abdominal wall reconstruction.

PURPOSE: Assess the utility of a hands-on workshop on abdominal wall reconstruction for teaching the posterior components separation (PCS) with transversus abdominis release. METHODS: Our department has been organizing a training course on abdominal wall reconstruction for the last 6 years. It is a 2-day-long course and 10-12 surgeons with experience in abdominal wall surgery attend to every course. The first day is dedicated to theoretical lectures and two simultaneous live surgeries, and the second day there is a cadaver dissection. Feedback from the trainees was collected at the end of the workshop. A survey was sent to all the surgeons who had completed the course at least a year ago, to inquire how the course had improved their surgical practice. RESULTS: From 2013 to April 2017, we have made 15 editions of the course. A total of 192 surgeons from Europe, South Africa and Middle East attended. All the surgeons answered the survey that was carried out at the end of the course. It showed a very high level of satisfaction in more than 98% of the cases. The second survey was answered by 79 surgeons (41.15%). 96% of the surgeons had modified, after attending the course, their way of dealing with complex abdominal wall problems. Only 29% of the surgeons had made a TAR before attending the course, while 86% are performing it after attending the course and 60% do it on a regular basis. In fact, 43% of surgeons have performed more than five posterior component separations in the last year. CONCLUSIONS: A workshop of abdominal wall surgery that combines live surgery, theoretical content and a cadaver lab can be a very useful tool to expand the use of new surgical techniques.

A giant exoplanet orbiting a very-low-mass star challenges planet formation models.

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.

Evaluation of the antioxidant activities of fatty polyhydroquinolines synthesized by Hantzsch multicomponent reactions.

Polyhydroquinolines (PHQs) are the unsymmetrical Hantzsch derivatives of 1,4-dihydropyridines with several biological applications. In this work, new fatty 2- and 3-substituted PHQ derivatives from different fatty acids and fatty alcohol feedstocks were synthesized at good yields via a four-component reaction (4CR). The antioxidant activities of fatty PHQs were investigated using three different antioxidant methods. The experiments showed that the compounds derived from 2-nitrobenzaldehyde and fatty palmitic (C16:0) and oleic (C18:1) chains showed better antioxidant activity. This revealed that combining the ortho NO2 group in the aromatic ring with the insertion of fatty chains in the PHQ core contributed to the antioxidant activity. However, among all the fatty PHQs tested, the fatty 2-substituted compound derived from oleyl alcohol and 2-nitrobenzaldehyde showed the highest antioxidant activity (EC50, 2.11-4.69 µM), which was similar to those of the antioxidant standards butylated hydroxytoluene (EC50, 1.98-6.47 µM) and vitamin E (EC50, 1.19-5.88 µM). In addition, this lipophilic compound showed higher antioxidant activity than the antihypertensive drug nifedipine (EC50, 49.25-126.86 µM). These results indicate that the new fatty PHQs may find novel applications as antioxidant additives.

Synthesis and antioxidant activity of new lipophilic dihydropyridines.

Dihydropyridines (DHPs) obtained from Hantzsch multicomponent reactions are an important pharmaceutical class of compounds marketed as antihypertensive (e.g., nifedipine, nitrendipine, and amlodipine) drugs. This study synthesized new symmetrical and unsymmetrical long-chain fatty DHPs using multicomponent reactions under metal-free conditions with sulfamic acid as a catalyst. The DHPs were tested for antioxidant activity using three different methods. The insertion of a long chain into the DHP core contributed to antioxidant potential, and compounds derived from nitro aldehydes have better antioxidant potential than the antihypertensive drug nifedipine. In addition, fatty analogs to nifedipine derived from palmitic and oleic chains showed similar antioxidant activity to the common standards butylated hydroxytoluene and vitamin E. These results showed that our new synthesized products may find novel applications as antioxidant additives or for tools for use in drug discovery.

New fatty dihydropyridines present cardioprotective potential in H9c2 cardioblasts submitted to simulated ischemia and reperfusion.

Nifedipine is a calcium channel blocker dihydropyridine that has been used in the treatment of hypertension. The production of reactive species and calcium overload are the main contributors to myocardial ischemia-reperfusion (I / R) injury. We investigated the ability of novel dihydropyridines (DHPs) to improve the effect of protecting against the injury induced by ischemia and reperfusion in cardioblasts when compared to nifedipine. Forty three DHPs were created varying the fatty chains derived from palmitic acid, stearic acid and oleic acids and aromatic moiety in addition to the addition of chemical elements such as chlorine, nitrogen dioxide, furfural, hydroxyl and methoxy. Cytotoxicity and inhibition of linoleic oxidation were evaluated for all new DHPs and also for nifedipine. The alpha-tocopherol and butylated hydroxytoluene (BHT) were used as antioxidants controls. The compounds with the best antioxidant potential were used in the ischemia and reperfusion (I / R) induction test in cardioblasts (H9c2). Cardioblasts were treated 24 h after assembly of plates and submitted to the ischemia simulation (30 min), after which, normoxia and cellular nutrition conditions were reestablished, simulating reperfusion (additional 30 min). Right after, cell viability, apoptosis, necrosis, and the generation of reactive oxygen species (ROS) were evaluated. Cell viability during I / R was not altered in cells treated with nifedipine, BHT and the new DHP composed of palmitic acid with hydroxyl group in the aromatic substituent. The other new DHPs increased cell viability during I / R simulation and reduced levels of reactive species compared to the I / R group, demonstrating the antioxidant capacity of the new DHPs. Therefore, DHPS with palmitic and oleic acids in the C3 and C5 position with NO2 or Cl in aromatic moiety, presented the highest antioxidant potential (linoleic oxidant test). The new DHPs increased cell viability during I / R simulation and reduced levels of reactive species compared to the ischemia and reperfusion group, demonstrating the antioxidant capacity of the new DHPs. Taken together, these results indicate that those new DHPs have a greater cardioprotective antioxidant capacity to face the damages of ischemia and reperfusion.

A candidate super-Earth planet orbiting near the snow line of Barnard's star.

Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.

Synthesis and antitumoral activity of novel analogues monastrol-fatty acids against glioma cells.

Monastrol is a small cell-permeable heterocyclic molecule that is recognized as an inhibitor of mitotic kinesin Eg5. Heterocyclic-fatty acid derivatives are a new class of compounds with a broad range of biological activities. This work describes a comparative study of the in vitro antitumoral activity of a series of new long-chain monastrol analogues against rat glioblastoma cells. The novel analogues C6-substituted monastrol and oxo-monastrol were synthesized via Biginelli multicomponent condensation of fatty ß-ketoester in good yields using a simple approach catalyzed by nontoxic and free-metal sulfamic acid. Following synthesis, their in vitro antitumoral activities were investigated. Notably, all analogues tested were active against rat glioblastoma cells. Superior activity was observed by analogues derived from palmitic and stearic fatty acid chains; these compounds were the most potent molecules, showing 13-fold higher potency than monastrol with IC50 values of 5.11 and 6.85 µM, respectively. These compounds could provide promising new lead derivatives for more potent antitumor drugs.

Circuitos de atención médica de la paciente con osteoporosis postmenopáusica en España / Medical care circuits for postmenopausal patients in Spain

Objetivos: Alcanzar un consenso sobre los circuitos de atención médica de la paciente con osteoporosis postmenopáusica (OPM), incluyendo los circuitos de derivación y manejo (herramientas de evaluación y pruebas médicas), identificando perfiles de acuerdo con la opinión de expertos en metabolismo óseo pertenecientes al Sistema de Salud Español. Material y métodos: Se empleó la técnica Delphi con dos rondas de consulta sucesivas. Participaron 38 expertos en el manejo de OPM pertenecientes a 14 sociedades científicas. La revisión de la literatura y la opinión del comité científico nutrieron el cuestionario. Los expertos expresaron su "deseo" (1=rechazo total; 9=deseo más fuerte) y "pronóstico" (1=no ocurrirá en absoluto; 9=ocurrirá con máxima probabilidad) acerca de las cuestiones planteadas. Se alcanzó consenso cuando el 75% o más de los participantes puntuaron 1-3 (desacuerdo) o 7-9 (acuerdo). Adicionalmente, los expertos se dividieron en 3 grupos de discusión para complementar la información según los perfiles de pacientes previamente hallados en el método Delphi. Resultados: Se alcanzó consenso en el 75% de las preguntas. Los expertos establecieron tres perfiles de pacientes con OPM: sin fractura, con fractura vertebral y con fractura no vertebral, así como los recursos diagnósticos y terapéuticos que conviene emplear en estas pacientes. La paciente sin fractura debería ser manejada por Atención Primaria o Reumatología y se utilizarán escalas para valorar el riesgo de fractura en fases tempranas de la enfermedad. La paciente con fractura vertebral crónica debería referirse a Reumatología y Rehabilitación, y se derivará a Reumatología; mientras que la paciente con fractura vertebral aguda debería ser tratada por Cirugía Ortopédica, y así es como posiblemente ocurrirá. El diagnóstico de la paciente con fractura vertebral estará basado principalmente en la radiografía. Para la evaluación de la progresión se deberían utilizar cuestionarios sobre la capacidad funcional y escalas del dolor. Sin embargo, no se utilizarán en la práctica habitual debido a la falta de tiempo. La paciente con fractura no vertebral debería ser y será referida a Cirugía Ortopédica, recomendando realizar 3-4 radiografías anuales para asegurar la consolidación de la fractura. Conclusiones: Los resultados del método Delphi muestran los circuitos de derivación de la paciente con OPM, que se concentran en Atención Primaria y Reumatología, cuando no existe fractura, y Cirugía Ortopédica, en caso de fractura (AU)

Objectives: To reach a consensus on the medical care circuits of patients with postmenopausal osteoporosis (PMO), including derivation and management (assessment tools and medical tests), identifying profiles according to the opinion of bone metabolism experts, from Spain’s Health Service. Material and methods: The Delphi technique was used with two successive consultation rounds, with 38 experts in PMO management belonging to 14 scientific societies taking part in the study. Review of literature and the opinion of the scientific committee rounded out the questionnaire. The experts expressed their "desire" (1=total rejection, 9=stronger desire) and "forecast" (1=will absolutely not occur; 9=will occur with maximum probability) about the issues raised. A consensus was reached when 75% or more of the participants scored 1-3 (disagreement) or 7-9 (agreement). In addition, experts were divided up into 3 discussion groups to complement the information according to patient profiles found previously in the Delphi method. Results: Consensus was reached on 75% of the questions. The experts established three profiles of PMO patients: no fracture, vertebral fracture and non-vertebral fracture, as well as the diagnostic and therapeutic resources recommended for these patients. The patient without a fracture should be managed in Primary Care or Rheumatology and scales will be used to evaluate fracture risk in early stages of the disease. The patient with chronic vertebral fracture should refer to Rheumatology and Rehabilitation, and will be Rheumatology, whereas the patient with acute vertebral fracture should be treated in Orthopedic Surgery, and this is how it will possibly happen. Diagnosis of vertebral fracture patients will be based mainly on x-rays. To assess progress, questionnaires on the functional capacity and pain scales are recommended. However, these will not be used due to the lack of time involved. The patient with non-vertebral fracture should be and will be referred to Orthopedic Surgery, with 3-4 radiographs recommended to ensure fracture consolidation. Conclusions: Delphi method results indicate that referral of PMO patients are concentrated in Primary Rheumatology, when there is no fracture, and Orthopedic Surgery, in the case of fracture (AU)

Proximate causes of the red face of the bald uakari monkey (Cacajao calvus).

In social species, such as primates, facial appearances transmit a variety of social signals. Although it is suggested that the intense red colour of the face of the bald uakari monkey might be an indicator of health, this hypothesis still has not been verified. This study describes the histological structure of the skin of the face in the bald uakari, compared with other non-red neotropical primates, to better understand the maintenance of its colour. The facial skin of the bald uakari monkey is characterized by a thinner epidermis, absence of melanin pigments and a high density of vascular capillaries that spread below the epidermis. These vascular capillaries are larger and more tortuous than in other neotropical primates. The skin of the face of the bald uakari monkey allows a direct external assessment of haematological status, suggesting that the colour of the face would be an honest indicator of health, but could also signal sexual or behavioural states.

Novel hybrid DHPM-fatty acids: synthesis and activity against glioma cell growth in vitro.

We described the first synthesis of fatty acid 3,4-dihydropyrimidinones (DHPM-fatty acids) using the Biginelli multicomponent reaction. Antiproliferative activity on two glioma cell lines (C6 rat and U-138-MG human) was also reported. The novel DHPM-fatty acids reduced glioma cell viability relative to temozolomide. Hybrid oxo-monastrol-palmitic acid was the most potent, reducing U-138-MG human cell viability by ca. 50% at 10 µM. In addition, the DHPM-fatty acids showed a large safety range to neural cells, represented by the organotypic hippocampal culture. These results suggest that the increased lipophilicity of DHPM-fatty acids offer a promising approach to overcoming resistance to chemotherapy and may play an important role in the development of new antitumor drugs.

Temporary abdominal closure with polytetrafluoroethylene prosthetic mesh in critically ill non-trauma patients.

BACKGROUND: Survival in critically ill non-trauma patients may be improved by performing temporary abdominal closure using different surgical techniques. We describe the use of expanded polytetrafluoroethylene (ePTFE) mesh for temporary abdominal closure in a group of critical patients. We also evaluate definitive abdominal wall closure in these patients once they are in a stable condition. METHOD: We conducted a study of 29 critically ill non-trauma patients who underwent temporary abdominal closure due to sepsis or abdominal compartment syndrome over 7 years at two university hospitals. We analysed factors related to surgical wound type and definitive abdominal wall closure. We evaluated the SAPS 3 severity score and used it to obtain expected mortality. We used the Clavien-Dindo System for Surgical Complications and the Ventral Hernia Working Group Classification during follow-up. RESULTS: Performing temporary abdominal closure with expanded polytetrafluoroethylene mesh was associated with a mortality rate of 20.68%, which was lower than the expected mortality calculated from the SAPS 3 severity score (38.87 ± 21.60). There was no fistula formation related with this type of prosthetic material. In our study group, definitive abdominal wall closure was performed in the 16 patients who survived (69.5%), and six of them underwent this procedure during the original hospital stay. CONCLUSION: Temporary abdominal closure with ePTFE mesh is an effective alternative in some circumstances. We observed a higher survival rate than the predicted figure and there were no cases of enteroatmospheric fistulae using this particular surgical technique. ePTFE facilitates definitive abdominal wall closure, once the patient is in a stable condition.