UVA-induced loss of quinolone antibacterial activity

Se investiga la actividad antibacteriana de soluciones de las quinolonas ácido nalidíxico, ciprofloxacino y levofloxacinoirradiadas mediante luz UVA. La fotólisis de las quinolonas produce una disminución de la actividad antibacterianaen cepas de E.coli y de S.aureus, evidenciándose un aumento de la concentración mínima inhibitoria de un 50%frente a las cepas ensayadas, en relación a las quinolonas no irradiadas. Se postula un mecanismo fotolítico radicalariocon la consecuente fotodegradación de la porción γ-piridona-β-carboxílica responsable de la actividad antibacterianaThe antibacterial activity of UVA-irradiated solutions of nalidixic acid, ciprofloxacin and levofloxacin was investigated.Photolysis of quinolones produced a decrease in antibacterial activity in strains of E. coli and S. aureus, becomingmanifest through an increase of 50% in the minimum inhibitory concentration of the drug as compared to nonirradiatedquinolones. In this study, it is suggested that a radical-mediated photolytic mechanism exists, leading to thephotodegradation of the γ-piridone-β-carboxylic group, which is the mediator that is responsible for the drugs antibacterialactivit

UVA-induced loss of quinolone antibacterial activity

Se investiga la actividad antibacteriana de soluciones de las quinolonas ácido nalidíxico, ciprofloxacino y levofloxacino irradiadas mediante luz UVA. La fotólisis de las quinolonas produce una disminución de la actividad antibacteriana en cepas de E.coli y de S.aureus, evidenciándose un aumento de la concentración mínima inhibitoria de un 50% frente a las cepas ensayadas, en relación a las quinolonas no irradiadas. Se postula un mecanismo fotolítico radicalario con la consecuente fotodegradación de la porción γ-piridona-β-carboxílica responsable de la actividad antibacteriana.The antibacterial activity of UVA-irradiated solutions of nalidixic acid, ciprofloxacin and levofloxacin was investigated. Photolysis of quinolones produced a decrease in antibacterial activity in strains of E. coli and S. aureus, becoming manifest through an increase of 50% in the minimum inhibitory concentration of the drug as compared to nonirradiated quinolones. In this study, it is suggested that a radical-mediated photolytic mechanism exists, leading to the photodegradation of the γ-piridone-β-carboxylic group, which is the mediator that is responsible for the drugs antibacterial activity

Tamoxifen disrupts the reproductive process in gilthead seabream males and modulates the effects promoted by 17alpha-ethynylestradiol

17α-ethynylestradiol (EE2), which is used in oral contraceptives and hormone replacement therapy, is a well documented estrogenic endocrine disruptor and an aquatic contaminant. In the present study, adult male specimens of the marine hermaphrodite teleost gilthead (Sparus aurata L.) were fed a diet containing tamoxifen (Tmx), an estrogen receptor ligand used in cancer therapy, alone or combined with EE2, for 25 days and then fed a commercial diet for a further 25 days (recovery period). The effects of short (5 days) and long (25 days) treatments on several reproductive and gonad immune parameters and the reversibility of the disruptive effects after the recovery period were examined. Our data showed that Tmx acted as an estrogenic endocrine disruptor as revealed by the increase in the hepatic transcription of the vitellogenin gene in males, the serum levels of 17β-estradiol and the gonad expression levels of the estrogen receptor α and G protein-coupled estrogen receptor genes, and the recruitment of leukocytes into the gonad, a well known estrogenic-dependent process in gilthead seabream males. On the other hand, Tmx also increased sperm concentration and motility as well as the serum levels of androgens and the expression levels of genes that codify for androgenic enzymes, while decreasing the expression levels of the gene that code for gonadal aromatase. When applied simultaneously, Tmx and EE2 could act in synergy or counteract, each other, depending on the parameter measured. The disruptive effect of EE2 and/or Tmx was not reversible after a 25 day recovery period.Postprin

TFAW survey II: 6 Newly Validated Planets and 13 Planet Candidates from K2

Searching for Earth-sized planets in data from Kepler's extended mission (K2) is a niche that still remains to be fully exploited. The TFAW survey is an ongoing project that aims to re-analyze all light curves in K2 C1-C8 and C12-C18 campaigns with a wavelet-based detrending and denoising method, and the period search algorithm TLS to search for new transit candidates not detected in previous works. We have analyzed a first subset of 24 candidate planetary systems around relatively faint host stars (10.9 < $K_{p}$ < 15.4) to allow for follow-up speckle imaging observations. Using VESPA and TRICERATOPS, we statistically validate six candidates orbiting four unique host stars by obtaining false-positive probabilities smaller than 1% with both methods. We also present 13 vetted planet candidates that might benefit from other, more precise follow-up observations. All of these planets are sub-Neptune-sized, with two validated planets and three candidates with sub-Earth sizes, and have orbital periods between 0.81 and 23.98 days. Some interesting systems include two ultra-short-period planets, three multi-planetary systems, three sub-Neptunes that appear to be within the small planet Radius Gap, and two validated and one candidate sub-Earths (EPIC 210706310, EPIC 210768568, and EPIC 246078343) orbiting metal-poor stars.Comment: Submitted to Monthly Notices of the Royal Astronomical Society. 25 pages, 14 figure

The Effect of a Physical Activity Program on the Total Number of Primary Care Visits in Inactive Patients: A 15-Month Randomized Controlled Trial

Abstract Background: Effective promotion of exercise could result in substantial savings in healthcare cost expenses in terms of direct medical costs, such as the number of medical appointments. However, this is hampered by our limited knowledge of how to achieve sustained increases in physical activity. Objectives: To assess the effectiveness of a Primary Health Care (PHC) based physical activity program in reducing the total number of visits to the healthcare center among inactive patients, over a 15-month period. Research Design: Randomized controlled trial. Subjects: Three hundred and sixty-two (n = 362) inactive patients suffering from at least one chronic condition were included. One hundred and eighty-three patients (n = 183; mean (SD); 68.3 (8.8) years; 118 women) were randomly allocated to the physical activity program (IG). One hundred and seventy-nine patients (n = 179; 67.2 (9.1) years; 106 women) were allocated to the control group (CG). The IG went through a three-month standardized physical activity program led by physical activity specialists and linked to community resources. Measures: The total number of medical appointments to the PHC, during twelve months before and after the program, was registered. Self-reported health status (SF-12 version 2) was assessed at baseline (month 0), at the end of the intervention (month 3), and at 12 months follow-up after the end of the intervention (month 15). Results: The IG had a significantly reduced number of visits during the 12 months after the intervention: 14.8 (8.5). The CG remained about the same: 18.2 (11.1) (P = .002). Conclusions: Our findings indicate that a 3-month physical activity program linked to community resources is a shortduration, effective and sustainable intervention in inactive patients to decrease rates of PHC visits. Trial Registration: ClinicalTrials.gov NCT0071483

Establishment and characterization of a sperm bank of Mediterranean seabass Dicentrarchus labrax (L., 1758) stock

Con el objetivo de conservar los recursos genéticos de la lubina Dicentrarchus labrax (L., 1758), se ha creado un banco de esperma con 42 machos de una población mediterránea. Se determinaron las características del esperma –concentración, motilidad y duración de la activación– que resultaron adecuadas para la fertilización artificial. La variabilidad genética de las lubinas procedentes del medio natural fue analizada mediante un conjunto de 10 loci microsatélites. A partir del genotipo de estos marcadores se obtuvo la huella de ADN de cada individuo con fines de identificación y estudios de paternidad. El análisis conjunto de todos los individuos permitió determinar los registros de las variables genéticas de este grupo. Los resultados muestran unos niveles altos de variabilidad genética representativos de una población natural y acentúan la importancia de este grupo como reservorio de esta especie en términos genéticosWith the aim of the conservation of the genetic resources of the European seabass Dicentrarchus labrax (L., 1758), a sperm bank of 42 males from a Mediterranean population has been established. The sperm characteristics –concentration, motility and duration of fertility– were assessed, and they proved suitable for artificial fertilization. The genetic structure of the original seabass broodstock from the wild was assessed by means of a set of 10 microsatellites. These genotype markers make it possible to obtain genetic fingerprinting from each individual for identification purposes. The population structure and genetic variability parameters found agree with those of natural populations from the same species, confirming its wild origin and enhancing its value as a genetic resource for the species in terms of genetic variabilityInstituto Español de Oceanografía. El proyecto RZ03-022 en el que se enmarca este trabajo ha sido financiado por el Programa Nacional de Recursos y Tecnologías Agroalimentarias, del Plan Nacional I+D+i del MCY

Spatio-temporal tumor heterogeneity in metastatic CRC tumors: a mutational-based approach

[EN] It is well known that activating mutations in the KRAS and NRAS genes are associated with poor response to anti-EGFR therapies in patients with metastatic colorectal cancer (mCRC). Approximately half of the patients with wild-type (WT) KRAS colorectal carcinoma do not respond to these therapies. This could be because the treatment decision is determined by the mutational profile of the primary tumor, regardless of the presence of small tumor subclones harboring RAS mutations in lymph nodes or liver metastases. We analyzed the mutational profile of the KRAS, NRAS, BRAF and PI3KCA genes using low-density microarray technology in samples of 26 paired primary tumors, 16 lymph nodes and 34 liver metastases from 26 untreated mCRC patients (n=76 samples). The most frequent mutations found in primary tumors were KRAS (15%) and PI3KCA (15%), followed by NRAS (8%) and BRAF (4%). The distribution of the mutations in the 16 lymph node metastases analyzed was as follows: 4 (25%) in KRAS gene, 3 (19%) in NRAS gene and 1 mutation each in PI3KCA and BRAF genes (6%). As expected, the most prevalent mutation in liver metastasis was in the KRAS gene (35%), followed by PI3KCA (9%) and BRAF (6%). Of the 26 cases studied, 15 (58%) displayed an overall concordance in the mutation status detected in the lymph node metastases and liver metastases compared with primary tumor, suggesting no clonal evolution. In contrast, the mutation profiles differed in the primary tumor and lymph node/metastases samples of the remaining 11 patients (48%), suggesting a spatial and temporal clonal evolution. We confirm the presence of different mutational profiles among primary tumors, lymph node metastases and liver metastases. Our results suggest the need to perform mutational analysis in all available tumor samples of patients before deciding to commence anti-EGFR treatment

Practical update of the Recommendations Published by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology (GPS) on the Treatment of Psoriasis with Biologic Therapy. Part 1. Concepts and General Management of Psoriasis with Biologic Therapy

Justificación y objetivos La aprobación de un gran número de nuevos fármacos en los últimos años y los cambios en el paradigma de tratamiento de la psoriasis hacen recomendable un nuevo documento de recomendaciones del GPS para el tratamiento de la psoriasis moderada-grave. Metodología Para la elaboración del consenso se siguió la metodología de grupos nominales, con ayuda de una scoping review. Tras designar a un coordinador, se seleccionó un grupo de integrantes del GPS. El coordinador definió los objetivos y puntos clave del documento y, con ayuda de un documentalista, se realizó una scoping review incluyendo datos de Medline, Embase y Cochrane Library (hasta enero del 2021). Se seleccionaron revisiones sistemáticas, metaanálisis y ensayos clínicos no incluidos en las mismas, así como estudios de calidad en vida real. Se revisaron otras guías de práctica clínica y documentos de consenso nacionales e internacionales sobre el manejo de la psoriasis moderada-grave. El coordinador generó una serie de recomendaciones preliminares que fueron evaluadas y modificadas en una reunión de grupo nominal. Tras varios procesos de revisión, que incluyeron la revisión externa por parte de los miembros del GPS, se redactó el documento definitivo. Resultados En el documento se incluyen principios generales sobre el tratamiento de los pacientes con psoriasis moderada-grave, la definición de objetivos terapéuticos y los criterios de indicación y selección de tratamiento tanto en primera como en sucesivas líneas terapéuticas de fármacos biológicos. Se abordan asimismo cuestiones prácticas como el fracaso terapéutico o el mantenimiento de la respuesta.Background and objectives A new, updated AEDV Psoriasis Group consensus document on the treatment of moderate to severe psoriasis was needed owing to the approval, in recent years, of a large number of new drugs and changes in the treatment paradigm. Methodology The consensus document was developed using the nominal group technique and a scoping review. First, a designated coordinator selected a group of Psoriasis Group members for the panel. The coordinator defined the objectives and key points for the document and, with the help of a documentalist, conducted a scoping review of articles in Medline, Embase, and the Cochrane Library up to January 2021. The review included systematic reviews and meta-analyses as well as clinical trials not included in those studies and high-quality real-world studies. National and international clinical practice guidelines and consensus documents on the management of moderate to severe psoriasis were also reviewed. Based on these reviews, the coordinator drew up a set of proposed recommendations, which were then discussed and modified in a nominal group meeting. After several review processes, including external review by other GPs members, the final document was drafted. Results The present guidelines include general principles for the treatment of patients with moderate to severe psoriasis and also define treatment goals and criteria for the indication of biologic therapy and the selection of initial and subsequent therapies. Practical issues, such as treatment failure and maintenance of response, are also addressed

Antimicrobial Activity of a Cationic Guanidine Compound against Two Pathogenic Oral Bacteria

This study evaluated the potential antimicrobial properties of a polyguanidine (CatDex) on two oral bacteria. Chlorhexidine gluconate 1340 μmoL L−1 (CHX 0.12%) was used as control. Streptococcus mutans (S. mutans) and Porphyromonas gingivalis (P. gingivalis) were grown in BHI media. Bacterial sensitivity and antimicrobial activity were determined by the minimum inhibitory concentration (MIC) and Kirby-Bauer methods. To study side effects, that is, toxicity, dental pulp stem cells (DPSCs) were used. Fluorometric cytotoxicity and confocal microscopy assays were used in order to test cell viability. CatDex inhibited growth of S. mutans at all concentrations and growth of P. gingivalis at all concentrations except 25 μmoL L−1. The MIC of CatDex was 50 μmoL L−1 for both S. mutans and P. gingivalis. The inhibition of bacteria exposed for 8 h at 50 μmoL L−1 of CatDex exhibited increased antimicrobial activity over time, with 91% inhibition in both bacteria. The antimicrobial activities of CatDex and CHX were similar when tested on two common bacteria. CatDex was significantly less toxic to DPSCs. CatDex toxicity depended on time and not on concentration. With regard to clinical relevance, CatDex may have potential as a novel antimicrobial agent. Further studies are in progress

‘People lie’: overcoming obstacles to incorporate social science research to biodiversity conservation

Mesmo com o reconhecimento da importância da interdisciplinaridade na conservação da biodiversidade, ainda há resistência em incorporar a pesquisa em ciências sociais (PCS) ao pensamento e à prática conservacionista. As razões para tal resistência podem ser resumidas em três afirmações gerais ainda comumente atribuídas à PCS: 'tem pouca utilidade' e 'menos rigor metodológico' quando comparada à pesquisa em ciências naturais e, sobretudo, é pouco confiável porque 'as pessoas mentem'. Neste ensaio, desenvolvido a partir da experiência dos participantes de uma comunidade de prática, formada por profissionais de diversas áreas e setores relacionados à conservação, e das discussões geradas nesse espaço de aprendizado coletivo, abordamos as limitações e os equívocos por trás das afirmações acima. A PCS não é menos útil na conservação e nem tem menos rigor metodológico do que a pesquisa em ciências naturais, e quando as pessoas mentem para o pesquisador o problema não está na pesquisa em si, mas na relação entre sujeito e pesquisador. Argumentamos que à medida que os conservacionistas se familiarizam com a PCS e que os princípios de equidade e justiça são incorporados aos valores e objetivos da conservação, a importância e necessidade da PCS na conservação tornam-se óbvias, e a falta de confiança entre pesquisador e sujeitos deixa de ser uma preocupação significativa. Capacitar, integrar e apoiar são nossas recomendações básicas para pesquisadores, educadores, gestores e tomadores de decisão nas áreas de conservação, ensino, publicação e financiamento, para que a PCS cumpra plenamente seu papel na conservação.Despite the acknowledged importance of interdisciplinarity in biodiversity conservation, there is still resistance to incorporate social science research (SSR) to both conservationist thinking and practice. The reasons for such a resistance can be summarized in three general statements still commonly attributed to SSR, namely: it is of 'little use' and it has 'less methodological rigor' than research in the natural sciences and, above all, it is unreliable because 'people lie'. The current essay was developed based on the experience of participants of a community of practice (formed by professionals from different fields and sectors  associated with conservation), as well as on discussions held in this space of collective learning. It addresses the limitations and misconceptions behind the aforementioned statements. SSR is not less useful in conservation and not less methodologically rigorous than research conducted in the natural sciences. When researchers are lied to, the problem does not lie on the research itself, but on the subject-researcher relationship. We herein argue that as conservationists become more familiar with SSR, and as principles like equity and justice are incorporated to conservation values and goals, both the importance and need of SSR in conservation become obvious, making the lack of trust between researcher and subjects no longer a significant concern. Increasing capacity, integrating and supporting are our basic recommendations for researchers, educators, managers and decision-makers in the conservation, teaching, publishing and funding fields, so that SSR can fully fulfill its role in conservation