Highly functionalized 2-oxopiperazine-based peptidomimetics: An approach to PAR1 antagonists

A series of pseudodipeptide-based chiral 1,3,4,5-tetrasubstituted-2- oxopiperazines has been designed and synthesized as potential PAR1 antagonists. These highly functionalized piperazines were synthesized from aromatic and basic amino acid derived Ψ[CH(CN)NH]pseudodipeptides through a four step pathway that involves reduction of the cyano group to build the 2-oxopiperazine ring, followed by selective functionalization at the N4-, N 1-positions, and at the exocyclic moiety at position C5. This regioselective functionalization required the fine tuning of reaction conditions. All new compounds were screened as inhibitors of human platelet aggregation induced by the PAR1 agonist SFLLRN and as cytotoxic agents in human cancer cell lines. Some of the compounds displayed moderate PAR1 antagonist activity, while, others were cytotoxic at μM concentration. No correlation was observed between both types of activities.Peer Reviewe

Potential factors influencing the condition of demersal sharks in the Mediterranean deep sea ecosystems

The Alboran Sea and the Balearic Islands are two contrasting areas in terms of primary productivity. The former is among the most productive areas of the whole Mediterranean Sea, whereas the Balearic Islands is among the less productive ones in the western Mediterranean. The two areas also show different patterns in the bottom trawl fishing footprint. In the Alboran Sea, the fishing effort on the upper slope is much higher than in Balearic Islands. However, the opposite applies to the middle slope, the vast majority of it remaining unexploited in Alboran Sea, whereas a widespread fishery targeting blue and red shrimp Aristeus antennatus develops in Balearic Islands. Galeus melastomus is a small demersal shark species inhabiting slope bottoms, where adults and juveniles are segregated and concentrate in the middle and upper slope, respectively. It feeds intensively on mesopelagic preys which, in turn, feed on low trophic level organisms close to primary producers. In this work we aimed to study the effect of surface primary production on the condition of deep sea demersal communities. We compared the condition, diet and potential intra- and inter-species competition for feeding resources in the juveniles of G. melastomus between Alboran Sea and Balearic Islands. The comparisons of Le Cren’s relative condition factor, and hepatosomatic and digestivosomatic indices evidenced an opposite pattern to that a priori expectable: better condition in the less productive area. The analysis of stomach contents showed similar diets in both areas, but lower food ingestion in Alboran Sea than in Balearic Islands. Different abundances of potential intra- and inter-specific competitors for feeding resources in the two areas, apparently linked to the different fishing footprints, seems the most likely explanation for the better nourished individuals in Balearic Islands. Whereas juveniles of G. melastomus dominate the shark community in the Balearic Islands upper slope, where the presence of adults of this species is almost negligible, in Alboran Sea this stratum is dominated by adults and potential competitors of other small demersal shark species. All shark species together, including G. melastomus, showed abundances 38% higher in Alboran than in Balearic Islands. Our results show that condition of deep sea demersal fish is ruled by complex inter-relationships among different factors, needing the combination of biological, ecological and fisheries knowledge to understand its variability.En prensa2,42

Assessment of genetic diversity of zoonotic Brucella spp. recovered from livestock in Egypt using multiple locus VNTR analysis

Brucellosis is endemic in most parts of Egypt, where it is caused mainly by Brucella melitensis biovar 3, and affects cattle and small ruminants in spite of ongoing efforts devoted to its control. Knowledge of the predominant Brucella species/strains circulating in a region is a prerequisite of a brucellosis control strategy. For this reason a study aiming at the evaluation of the phenotypic and genetic heterogeneity of a panel of 17 Brucella spp. isolates recovered from domestic ruminants (cattle, buffalo, sheep, and goat) from four governorates during a period of five years (2002-2007) was carried out using microbiological tests and molecular biology techniques (PCR, MLVA-15, and sequencing). Thirteen strains were identified as B. melitensis biovar 3 while all phenotypic and genetic techniques classified the remaining isolates as B. abortus (n = 2) and B. suis biovar 1 (n = 2). MLVA-15 yielded a high discriminatory power (h = 0.801), indicating a high genetic diversity among the B. melitensis strains circulating among domestic ruminants in Egypt. This is the first report of the isolation of B. suis from cattle in Egypt which, coupled with the finding of B. abortus, suggests a potential role of livestock as reservoirs of several zoonotic Brucella species in the region

Association between COVID-19 prognosis and disease presentation, comorbidities and chronic treatment of hospitalized patients

mportance The rapid pandemic expansion of the disease caused by the new SARS-CoV-2 virus has compromised health systems worldwide. Knowledge of prognostic factors in affected patients can help optimize care. Objective The objective of this study was to analyze the relationship between the prognosis of COVID-19 and the form of presentation of the disease, the previous pathologies of patients and their chronic treatments. Design, participants and locations This was an observational study on a cohort of 418 patients admitted to three regional hospitals in Catalonia (Spain). As primary outcomes, severe disease (need for oxygen therapy via nonrebreather mask or mechanical ventilation) and death were studied. Multivariate binary logistic regression models were performed to study the association between the different factors and the results. Results Advanced age, male sex and obesity were independent markers of poor prognosis. The most frequent presenting symptom was fever, while dyspnea was associated with severe disease and the presence of cough with greater survival. Low oxygen saturation in the emergency room, elevated CRP in the emergency room and initial radiological involvement were all related to worse prognosis. The presence of eosinophilia (% of eosinophils) was an independent marker of less severe disease. Conclusions This study identified the most robust markers of poor prognosis for COVID-19. These results can help to correctly stratify patients at the beginning of hospitalization based on the risk of developing severe disease

Host virus and pneumococcus-specific immune responses in high-count monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia: implications for disease progression

[EN]Patients diagnosed with chronic lymphocytic leukemia (CLL) display a high incidence of infections due to an associated immunodeficiency that includes hypogammaglobulinemia. A higher risk of infections has also been recently reported for high-count monoclonal B-cell lymphocytosis, while no information is available in low-count monoclonal B-cell lymphocytosis. Here, we evaluated the status of the humoral immune system in patients with chronic lymphocytic leukemia (n=58), as well as in low- (n=71) and high- (n=29) count monoclonal B-cell lymphocytosis versus healthy donors (n=91). Total free plasma immunoglobulin titers and specific levels of antibodies against cytomegalovirus, Epstein-Barr virus, influenza and S.pneumoniae were measured by nephelometry and ELISA-based techniques, respectively. Overall, our results show that both CLL and high-count monoclonal B-cell lymphocytosis patients, but not low-count monoclonal B-cell lymphocytosis subjects, present with relatively high levels of antibodies specific for the latent viruses investigated, associated with progressively lower levels of S.pneumoniae-specific immunoglobulins

Development of lessons on chemical and biological reactors in Moodle platform

En este proyecto docente se han desarrollado una serie de actividades académicamente dirigidas dedicadas a los reactores químicos y biológicos, en concreto, se ha empleado una herramienta denominada lección que se encuentra disponible a través de la plataforma virtual Moodle, dichas lecciones se basan en una serie de ventanas secuenciales que permiten profundizar en todos los conceptos fundamentales de los reactores químicos y/o biológicos y, a través de diversas cuestiones complementarias sobre el tema, incluidas durante el desarrollo de dicha lección, permite al alumno realizar un aprendizaje más activo que favorece la consolidación de los conceptos de forma gradual. Previo al estudio de los reactores químicos y/o biológicos es necesario tener en cuenta diversos aspectos químicos, físicos, matemáticos, biológicos e ingenieriles que han de considerarse para desarrollar los aspectos fundamentales básicos para poder alcanzar dicho objetivo y se pretende facilitar esta labor al alumnado con el empleo de las lecciones elaboradas. Previamente a la elaboración de las lecciones se ha realizado una importante labor de preparación y síntesis de toda la información, posteriormente se han desarrollado diferentes lecciones para los conceptos tratados en cada uno de los temas implicados en la elaboración de este proyecto docente y tras una profunda revisión se han puesto a disposición de los alumnos.In this teaching project have developed a series of academic activities devoted to the chemical and biological reactors, in particular, it has been using a tool called lesson which is available through the Moodle virtual platform, these lessons are based on a series of sequential windows allowing to delve into all the fundamental concepts of chemical and/or biological reactors and through various complementary on the theme, including issues during the development of this lesson, students perform a more active learning that promotes the consolidation of concepts gradually. Prior to the study of chemical reactors and/or biological is necessary to take account of various chemical, physical, mathematical, biological and engineering aspects that are to be considered to develop the basic fundamentals to achieve the aim and is intended to facilitate this work to the students with the use of elaborate lessons. Important preparation work has been prior to the preparation of the lessons and synthesis of information, have subsequently developed different lessons for the concepts dealt with in each of the issues involved in the development of this educational project and after a thorough review have been available to the students