Boron- and phosphorus-containing molecular/nano platforms: exploiting pathological redox imbalance to fight cancer.

Cancer is currently the second leading cause of death globally. Despite multidisciplinary efforts, therapies to fight various types of cancer still remain inefficient. Reducing high recurrence rates and mortality is thus a major challenge to tackle. In this context, redox imbalance is an undervalued characteristic of cancer. However, it may be targeted by boron- and phosphorus-containing materials to selectively or systemically fight cancer. In particular, boron and phosphorus derivatives are attractive building blocks for rational drug discovery due to their unique and wide regioselective chemistry, high degree of tuneability and chemical stability. Thus, they can be meticulously employed to access tunable molecular platforms to selectively exploit the redox imbalance of cancer cells towards necrosis/apoptosis. This field of research holds a remarkable potential; nevertheless, it is still in its infancy. In this mini-review, we underline recent advances in the development of boron- or phosphorus-derivatives as molecular/nano platforms for rational anticancer drug design. Our goal is to provide comprehensive information on different methodologies that bear an outstanding potential to further develop this very promising field of research.

Evaluation of Inhibitory Activity In Silico of In-House Thiomorpholine Compounds between the ACE2 Receptor and S1 Subunit of SARS-CoV-2 Spike.

At the end of 2019, the world was struck by the COVID-19 pandemic, which resulted in dire repercussions of unimaginable proportions. From the beginning, the international scientific community employed several strategies to tackle the spread of this disease. Most notably, these consisted of the development of a COVID-19 vaccine and the discovery of antiviral agents through the repositioning of already known drugs with methods such as de novo design. Previously, methylthiomorphic compounds, designed by our group as antihypertensive agents, have been shown to display an affinity with the ACE2 (angiotensin converting enzyme) receptor, a key mechanism required for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) entry into target cells. Therefore, the objective of this work consists of evaluating, in silico, the inhibitory activity of these compounds between the ACE2 receptor and the S1 subunit of the SARS-CoV-2 spike protein. Supported by the advances of different research groups on the structure of the coronavirus spike and the interaction of the latter with its receptor, ACE2, we carried out a computational study that examined the effect of in-house designed compounds on the inhibition of said interaction. Our results indicate that the polyphenol LQM322 is one of the candidates that should be considered as a possible anti-COVID-19 agent.

Affordability and quality of cross-border reproductive care from the perspective of surrogacy mediating agencies in Spain / Asequibilidad y calidad de la atención reproductiva transfronteriza desde la perspectiva de las agencias mediadoras de gestación por sustitución en españa

RESUMEN La gestación por sustitución contribuye a la transformación de las concepciones sociales de la filiación y los cambios en las estrategias reproductivas de las familias. En la presente contribución se relaciona la teoría de la atención reproductiva transfronteriza con las teorías posmodernas de la vida familiar, con el propósito de explorar qué temáticas, elementos y contenidos utilizan las agencias intermediarias de gestación por sustitución que tienen por destinatarios a las madres y padres de intención españoles. Se utiliza la metodología cualitativa y la técnica de análisis de contenido temático tras el registro de la información online recogida de las agencias. Los resultados evidencian el papel de estas agencias mediadoras en los procesos de gestación por sustitución en España, además de generar conocimiento en el área de las nuevas formas familiares constituidas mediante técnicas de reproducción asistida.

ABSTRACT Substitution pregnancy contributes to the transformation of social conceptions of filiation and changes in the reproductive strategies of families. This contribution relates the theory of cross-border reproductive care with post-modern theories of family life in order to explore which themes, elements and contents are used by intermediary surrogate pregnancy agencies which target Spanish mothers and fathers. The qualitative methodology and the technique of thematic content analysis after registration of the online information collected from the agencies is used. The results show the role of these intermediary agencies in the process of gestation by substitution in Spain, as well as generating knowledge in the area of new family forms constituted by assisted reproduction techniques.

A simple phosphorus determination in walnuts and assessment of the assimilable fraction.

In this work, a method for the determination of phosphorus in walnuts has been developed due to the fact that there is no specific method for this purpose. A closed-vessel microwave-assisted digestion of the samples was optimized and a modified molybdenum blue spectrophotometric method was carried out with excellent precision and selectivity. To differentiate assimilable and non-assimilable phosphorus, an easy extraction procedure using 1 M NH4Cl was used. FTIR spectra ensured that the phytate extraction was successful. A sampling of thirteen different walnuts available to consumers from different crops and geographical origin was performed. Comparative statistical tools to differentiate walnuts were also carried out. Significant differences based on total content of phosphorus were obtained. Finally, a correlation study between total phosphorus concentration and the non-assimilable fraction showed a non-linear relationship (R2 = 0.435). Therefore, in relation to consumer health the total phosphorus determination must be complemented with information about assimilable phosphorus.

Xanthomonas prunicola sp. nov., a novel pathogen that affects nectarine (Prunus persica var. nectarina) trees.

Three isolates obtained from symptomatic nectarine trees (Prunus persica var. nectarina) cultivated in Murcia, Spain, which showed yellow and mucoid colonies similar to Xanthomonas arboricola pv. pruni, were negative after serological and real-time PCR analyses for this pathogen. For that reason, these isolates were characterized following a polyphasic approach that included both phenotypic and genomic methods. By sequence analysis of the 16S rRNA gene, these novel strains were identified as members of the genus Xanthomonas, and by multilocus sequence analysis (MLSA) they were clustered together in a distinct group that showed similarity values below 95 % with the rest of the species of this genus. Whole-genome comparisons of the average nucleotide identity (ANI) of genomes of the strains showed less than 91 % average nucleotide identity with all other species of the genus Xanthomonas. Additionally, phenotypic characterization based on API 20 NE, API 50 CH and BIOLOG tests differentiated the strains from the species of the genus Xanthomonas described previously. Moreover, the three strains were confirmed to be pathogenic on peach (Prunus persica), causing necrotic lesions on leaves. On the basis of these results, the novel strains represent a novel species of the genus Xanthomonas, for which the name Xanthomonas prunicola is proposed. The type strain is CFBP 8353 (=CECT 9404=IVIA 3287.1).

Library of Norcoclaurine Synthases and Their Immobilization for Biocatalytic Transformations.

Norcoclaurine synthases (NCS), catalyzing a Pictet-Spengler reaction in plants as one of the first enzymes in the biosynthetic benzylisoquinoline pathway, are investigated for biocatalytic transformations. The library of NCS available is extended by two novel NCSs from Argemone mexicana (AmNCS1, AmNCS2) and one new NCS from Corydalis saxicola (CsNCS); furthermore, it is shown that the NCS from Papaver bracteatum (PbNCS) is a highly productive catalyst leading to the isoquinoline product with up to >99% e.e. Under certain conditions lyophilized whole Escherichia coli cells containing the various overexpressed NCS turned out to be suitable catalysts. The reaction using dopamine as substrate bears several challenges such as the spontaneous non-stereoselective background reaction and side reactions. The PbNCS enzyme is successfully immobilized on various carriers whereby EziG3 proved to be the best suited for biotransformations. Dopamine showed limited stability in solution resulting in the coating of the catalyst over time, which could be solved by the addition of ascorbic acid (e.g., 1 mg ml-1 ) as antioxidant.

Lateral flow immunoassay for on-site detection of Xanthomonas arboricola pv. pruni in symptomatic field samples.

Xanthomonas arboricola pv. pruni is a quarantine pathogen and the causal agent of the bacterial spot disease of stone fruits and almond, a major threat to Prunus species. Rapid and specific detection methods are essential to improve disease management, and therefore a prototype of a lateral flow immunoassay (LFIA) was designed for the detection of X. arboricola pv. pruni in symptomatic field samples. It was developed by producing polyclonal antibodies which were then combined with carbon nanoparticles and assembled on nitrocellulose strips. The specificity of the LFIA was tested against 87 X. arboricola pv. pruni strains from different countries worldwide, 47 strains of other Xanthomonas species and 14 strains representing other bacterial genera. All X. arboricola pv. pruni strains were detected and cross-reactions were observed only with four strains of X. arboricola pv. corylina, a hazelnut pathogen that does not share habitat with X. arboricola pv. pruni. The sensitivity of the LFIA was assessed with suspensions from pure cultures of three X. arboricola pv. pruni strains and with spiked leaf extracts prepared from four hosts inoculated with this pathogen (almond, apricot, Japanese plum and peach). The limit of detection observed with both pure cultures and spiked samples was 104 CFU ml-1. To demonstrate the accuracy of the test, 205 samples naturally infected with X. arboricola pv. pruni and 113 samples collected from healthy plants of several different Prunus species were analyzed with the LFIA. Results were compared with those obtained by plate isolation and real time PCR and a high correlation was found among techniques. Therefore, we propose this LFIA as a screening tool that allows a rapid and reliable diagnosis of X. arboricola pv. pruni in symptomatic plants.

Multilocus Variable Number of Tandem Repeat Analysis Reveals Multiple Introductions in Spain of Xanthomonas arboricola pv. pruni, the Causal Agent of Bacterial Spot Disease of Stone Fruits and Almond.

Xanthomonas arboricola pv. pruni is the causal agent of the bacterial spot disease of stone fruits, almond and some ornamental Prunus species. In Spain it was first detected in 2002 and since then, several outbreaks have occurred in different regions affecting mainly Japanese plum, peach and almond, both in commercial orchards and nurseries. As the origin of the introduction(s) was unknown, we have assessed the genetic diversity of 239 X. arboricola pv. pruni strains collected from 11 Spanish provinces from 2002 to 2013 and 25 reference strains from international collections. We have developed an optimized multilocus variable number of tandem repeat analysis (MLVA) scheme targeting 18 microsatellites and five minisatellites. A high discriminatory power was achieved since almost 50% of the Spanish strains were distinguishable, confirming the usefulness of this genotyping technique at small spatio-temporal scales. Spanish strains grouped in 18 genetic clusters (conservatively delineated so that each cluster contained haplotype networks linked by up to quadruple-locus variations). Furthermore, pairwise comparisons among populations from different provinces showed a strong genetic differentiation. Our results suggest multiple introductions of this pathogen in Spain and redistribution through contaminated nursery propagative plant material.

Evaluation of a real-time PCR and a loop-mediated isothermal amplification for detection of Xanthomonas arboricola pv. pruni in plant tissue samples.

Operational capacity of real-time PCR and loop-mediated isothermal amplification (LAMP) diagnostic assays for detection of Xanthomonas arboricola pv. pruni was established in a ring-test involving four laboratories. Symptomatic and healthy almond leaf samples with two methods of sample preparation were analyzed. Kappa coefficient, sensitivity, specificity, likelihood ratios and post-test probability of detection were estimated to manage the risk associated with the use of the two methods.

The effect of caffeic acid phenethyl ester analogues in a modified resistant hepatocyte model.

We present a study of the chemoprotective effects of two caffeic acid phenethyl ester (CAPE)-related structures: LQM717 and LQM706. The modified resistant hepatocyte model in rats was used to study the chemoprevention of these CAPE analogues, which are inexpensive and easily obtained. In the liver cancer model used, we detected extensive necrosis and lipid peroxidation after 24 h, many altered hepatic foci, putatively preneoplastic lesions with γ-glutamyl transpeptidase staining after 30 days, and liver tumors at 12 months. We tested the effect of the CAPE analogues on necrosis, lipid peroxidation, proliferation, p65 activation, altered hepatic foci, and tumors. Both compounds exerted protective effects on lipid peroxidation, necrosis, cell proliferation, p65 activation, and preneoplastic lesions. Rats under a carcinogenic protocol showed a 52, 71.74, and 51.6% decrease in the number of preneoplastic nodules when pretreated with CAPE, LQM706, and LQM717, respectively. At 12 months after carcinogenic treatment, eight of eight rats developed liver cancer, whereas in the group of rats that received pretreatment with CAPE, LQM706, or LQM717, 62.5, 83.3, or 42.85%, respectively, had tumors. In conclusion, LQM717 has the potential to enhance chemoprotection activity much better than CAPE by markedly reducing the formation of liver cancers in this model, and this is a compound that is easy to obtain.

Colecistectomía laparoscópica en pacientes octogenarios. Estudio comparativo entre dos poblaciones en edad geriátrica / Laparoscopic cholecystectomy in octogenarian patients. A comparative study between two geriatric population groups

Introducción: En el presente artículo analizamos los resultados y complicaciones de la colecistectomía laparoscópica en octogenarios. Pacientes y método: Estudio retrospectivo sobre pacientes con edad ≥80 años, sometidos a una colecistectomía laparoscópica entre enero de 2002 y agosto de 2007. Los parámetros analizados fueron: presentación, estado general, riesgo anestésico, tasa de conversión, morbilidad y estancia hospitalaria. Se realizó una comparación con pacientes geriátricos de entre 70 y 79 años. Para el análisis estadístico utilizamos la prueba de la χ2 y la t de Student. La significación se estableció para valores de p<0,05. Resultados: Se intervino a 64 pacientes (el 63%, mujeres), con una media de edad de 83,7 años. La cirugía fue programada en 40 (62,5%) casos y urgente en 24. La tasa de conversión fue del 10,9% y la media de estancia hospitalaria, 3,9 días. Dos enfermos fueron reoperados y hubo dos decesos. Conclusiones: La colecistectomía laparoscópica es la técnica de elección para el tratamiento de la colelitiasis sintomática en octogenarios. La colecistitis aguda del anciano debe ser tratada mediante abordaje laparoscópico, salvo contraindicación, preferentemente antes de que aparezcan complicaciones (AU)

Introduction: In the current article, we analyse the results and complications of laparoscopic cholecystectomy in octogenarian patients. Patients and method: Retrospective study in patients older than 80 years, who underwent laparoscopic cholecystectomy between January 2002 and August 2007. Variables analysed were presentation, physical condition, anaesthetic risk, conversion rate, morbidity and hospital stay. A comparison was made with patients aged between 70 and 79 years old. The χ2 and Student's t tests were used for statistical analysis. The level of significance was defined as a p value less than 0.05. Results: A total of 64 patients were operated on, of which 39 (63%) were women and 25 men, with a mean age 83.7 years. Surgery was scheduled in 40 (62.5%) cases and urgent in 24 cases. The conversion rate to open cholecystectomy was 10.9% and the average hospital stay was 3.9 days. Two patients required re-intervention and two patients died. Conclusions: Laparoscopic cholecystectomy is the treatment of choice for symptomatic cholelithiasis in octogenarians. The laparoscopic approach should be considered for the management of acute cholecystitis in the very old (except where contraindicated) before the development of complications (AU)

[Laparoscopic cholecystectomy in octogenarian patients. A comparative study between two geriatric population groups]. / Colecistectomía laparoscópica en pacientes octogenarios. Estudio comparativo entre dos poblaciones en edad geriátrica.

INTRODUCTION: In the current article, we analyse the results and complications of laparoscopic cholecystectomy in octogenarian patients. PATIENTS AND METHOD: Retrospective study in patients older than 80 years, who underwent laparoscopic cholecystectomy between January 2002 and August 2007. Variables analysed were presentation, physical condition, anaesthetic risk, conversion rate, morbidity and hospital stay. A comparison was made with patients aged between 70 and 79 years old. The chi(2) and Student's t tests were used for statistical analysis. The level of significance was defined as a p value less than 0.05. RESULTS: A total of 64 patients were operated on, of which 39 (63%) were women and 25 men, with a mean age 83.7 years. Surgery was scheduled in 40 (62.5%) cases and urgent in 24 cases. The conversion rate to open cholecystectomy was 10.9% and the average hospital stay was 3.9 days. Two patients required re-intervention and two patients died. CONCLUSIONS: Laparoscopic cholecystectomy is the treatment of choice for symptomatic cholelithiasis in octogenarians. The laparoscopic approach should be considered for the management of acute cholecystitis in the very old (except where contraindicated) before the development of complications.

Colecistectomía laparoscópica en el paciente geriátrico con edad superior a 80 años / No disponible

Fundamentos. En el presente artículo analizamos los resultados y complicaciones de la colecistectomía laparoscópica en pacientes octogenarios. El objetivo es establecer si la cirugía endoscópica, programada o urgente, es el tratamiento electivo de la colelitiasis en edades extremas. Métodos: Realizamos un estudio retrospectivo sobre pacientes con edad igual o superior a 80 años, sometidos a una colecistectomía laparoscópica entre enero de 2002 y enero de 2006. Los principales parámetros analizados fueron: epidemiología, forma de presentación, valoración del estado general y del riesgo anestésico, tasa de conversión, morbilidad y estancia hospitalaria. Resultados: En el periodo estudiado se intervinieron 43 pacientes, 27 mujeres (63%) y 16 hombres con una edad media de 83.5 años (máxima 92). La cirugía fue programada en 28 casos (65%) y urgente en 15. La tasa de conversión a colecistectomía abierta fue del 11.6% y la estancia hospitalaria media de 3.9 días. Dos enfermos precisaron de una reintervención y hubo un fallecido. Conclusiones: La colecistectomía laparoscópica es la técnica de elección para el tratamiento de la colelitiasis sintomática en octogenarios. La colecistitis aguda del anciano debe ser tratada mediante abordaje laparoscópico, salvo contraindicación, preferentemente antes de aparezcan complicaciones (AU)

Background: In the current article, we analyse the results and complications of laparoscopic cholecystectomy in octogenarian patients. The aim is to determine whether the open procedure (either programmed or emergent surgery) is the elective treatment of cholelithiasis in extremely elderly patients. Methods: We implement a retrospective study in patients aged 80 years or older. They under went laparoscopic cholecystectomy between January 2002 and January 2006. Variables analysed were epidemiology, initial presentation, assessment of physical condition and anesthetic risk, conversion rate, morbidity and hospital stay. Results: The study group consisted of 43 patients, 27 women (63%) and 16 men, mean age 83.5 years (maximum 92). Programmed surgery was attempted in 28 cases (65%) and emergent 15 cases. The conversion rate to open cholecystectomy was 11.6% and the average hospital stay was 3.9 days. Two patients required reintervention and one patient died. Conclusions: Laparoscopic cholecystectomy is elective treatment for symptomatic cholelithiasis in octogenarian people. The management of acute cholecystitis in the extremely elderly should be considered for laparoscopic approach (except contraindication) before the development of complications (AU)

Hospital-in-the-home treatment of surgical infectious diseases: an economic analysis.

BACKGROUND: A growing number of surgical infections can be treated safely and effectively with parenteral antimicrobial therapy in the patient's home. Our objective was to define the economic impact of a hospital-in-the-home unit (HITH) introduced into a surgical unit. METHODS: Patients admitted to the HITH must be assessed thoroughly for suitability, including clinical stability and social circumstances, and both patient and caregiver consent must be obtained. The HITH received all stable surgical patients with complicated infections and an expected long-term stay. A total of 150 patients were enrolled during a 12-month period. Patients were reviewed daily to monitor the progress of therapy and check for possible complications. Antibiotic selection was based on appropriate prescribing principles rather than dosing convenience. Innovative dosing regimens were included, such as once-daily aminoglycosides, continuous-infusion beta-lactams, once- or twice-daily cephalosporins, and oral fluoroquinolones in order to provide effective therapy for a wide range of infections that previously would have required in-hospital care. Economic efficiency for both the surgical and the HITH unit was assessed by examining Diagnosis-Related Group (DRG)-based clinical processes, profits and losses of each clinical process, and a quantitative model for performance evaluation and benchmarking (data envelopment analysis; DEA). RESULTS: The mean stay in the surgical unit was decreased (3.95 days) while increasing the case mix (1.42). At the same time, HITH patients had a mean stay of 8.69 days with a stable case mix of 1.61. The economic benefit of both units increased in the surgical unit because of a shorter stay and in the HITH secondary to greater impact of the case mix while maintaining the mean stay. CONCLUSIONS: Appropriate use of HITH leads to greater patient and caregiver satisfaction, efficient in-hospital bed use, and financial efficiencies. Patients receiving intravenous antibiotics, wound care, parenteral nutrition, or transfusions do not always need to be in the hospital.

Safenectomía ambulatoria y con ingreso de 12 horas. Revisión crítica y líneas de mejora / Ambulatory and short-stay saphenectomy. A review of current practice and suggestions for improvement

El tratamiento de la insuficiencia venosa crónica mediante safenectomía sin ingreso mejora la calidad del proceso quirúrgico: menos morbilidad, elevada satisfacción del paciente y contención del gasto sanitario. El desarrollo de una trayectoria clínica específica dentro de la Vía Clínica de la Safenectomía permite una buena selección de candidatos para la cirugía sin hospitalización y estandarizar las diversas actuaciones médicas, administrativas y logísticas. En el presente artículo realizamos una revisión de nuetras pautas terapéuticas actuales y estudiamos el desarrollo de una trayectoria clínica para la safenectomía ambulatoria en nuestro centro hospitalario

Treatment of chronic venous insufficiency by means of ambulatory saphenectomy improves the quality of surgical process: low morbidity, great patient satisfaction and the most cost-effective way. Implementation of an Anticipated Recovery Pathway allows a good selection of candidates for Day surgery and hte standarization of different medical, administrative and logistical actions. In this article, we study the development of an anticipated Recovery pathway of ambulatory saphenectomy in our hospital

Abdomen agudo por linfangioma quístico multilocular / Acute abdomen due to multilocular cystic lymphangioma

No disponible