Synthesis and Evaluation of Cytostatic and Antiviral Activities of 3′ and 4′-Avarone Derivatives

A series of 3′ and 4′-substituted avarone derivatives were synthesized and tested in culture systems as antitumour and antiviral agents in comparison to avarol and avarone. 3′-alkylamino derivatives showed potent cytostatic activities against murine L1210 and human B (Raji) and T (C8166, H9) lymphoblast cells (ID50 range 1.7–3.7 μm). Avarol and avarone were six times less active. While none of the derivatives showed anti-human immunodeficiency virus (HIV) activity superior to that of the parent compounds, most of them, avarol and avarone included, were potent and selective inhibitors of poliovirus multiplication

Strong Casimir force reduction through metallic surface nanostructuring

The Casimir force between bodies in vacuum can be understood as arising from their interaction with an infinite number of fluctuating electromagnetic quantum vacuum modes, resulting in a complex dependence on the shape and material of the interacting objects. Becoming dominant at small separations, the force plays a significant role in nanomechanics and object manipulation at the nanoscale, leading to a considerable interest in identifying structures where the Casimir interaction behaves significantly different from the well-known attractive force between parallel plates. Here we experimentally demonstrate that by nanostructuring one of the interacting metal surfaces at scales below the plasma wavelength, an unexpected regime in the Casimir force can be observed. Replacing a flat surface with a deep metallic lamellar grating with sub-100 nm features strongly suppresses the Casimir force and for large inter-surfaces separations reduces it beyond what would be expected by any existing theoretical prediction.Comment: 11 pages, 8 figure

Beta catenin and cytokine pathway dysregulation in patients with manifestations of the "PTEN hamartoma tumor syndrome"

Background. The "PTEN hamartoma tumor syndrome" (PHTS) includes a group of syndromes caused by germline mutations within the tumor suppressor gene "phosphatase and tensin homolog deleted on chromosome ten" (PTEN), characterized by multiple polyps in the gastrointestinal tract and by a highly increased risk of developing malignant tumours in many tissues. The current work clarifies the molecular basis of PHTS in three unrelated Italian patients, and sheds light on molecular pathway disregulation constitutively associated to PTEN alteration. Methods. We performed a combination of RT-PCR, PCR, sequencing of the amplified fragments, Real Time PCR and western blot techniques. Results. Our data provide the first evidence of β-catenin accumulation in blood cells of patients with hereditary cancer syndrome caused by germ-line PTEN alteration. In addition, for the first time we show, in all PHTS patients analysed, alterations in the expression of TNFα, its receptors and IL-10. Importantly, the isoform of TNFRI that lacks the DEATH domain (TNFRSF1β) was found to be overexpressed. Conclusion. In light of our findings, we suggest that the PTEN pathway disregulation could determine, in non-neoplastic cells of PHTS patients, cell survival and pro-inflammatory stimulation, mediated by the expression of molecules such as β-catenin, TNFα and TNFα receptors, which could predispose these patients to the development of multiple cancers

Educational and labor wastage of doctors in Mexico: towards the construction of a common methodology

BACKGROUND: This paper addresses the problem of wastage of the qualified labor force, which takes place both during the education process and when trained personnel try to find jobs in the local market. METHODS: Secondary sources were used, mainly the Statistical yearbooks of the National Association of Universities and Higher Education Institutions (ANUIES in Spanish). Also, the 2000 Population Census was used to estimate the different sources of labor market wastage. The formulas were modified to estimate educational and labor wastage rates. RESULTS: Out of every 1000 students who started a medical training in 1996, over 20% were not able to finish the training by 2000. Furthermore, out of every 1000 graduates, 31% were not able to find a remunerated position in the labor market that would enable them to put into practice the abilities and capacities obtained at school. Important differences can be observed between generalists and specialists, as well as between men and women. In the case of specialists and men, lower wastage rates can be observed as compared to the wastage rates of generalists and women. A large percentage of women dedicate themselves exclusively to household duties, which in labor terms represents a wastage of their capacity to participate in the production of formal health services. CONCLUSION: Women are becoming a majority in most medical schools, yet their participation in the labor market does not reflect the same trend. Among men, policies should be formulated to incorporate doctors in the specific health field for which they were trained. Regarding women, specific policies should target those who are dedicated full-time to household activities in order to create the possibility of having them occupy a remunerated job if they are willing to do so. Reducing wastage at both the educational and labor levels should improve the capacity of social investment, thereby increasing the capacity of the health system as a whole to provide services, particularly to those populations who are most in need

Detection and Characterization of CD133+ Cancer Stem Cells in Human Solid Tumours

Osteosarcoma is the most common primary tumour of bone. Solid tumours are made of heterogeneous cell populations, which display different goals and roles in tumour economy. A rather small cell subset can hold or acquire stem potentials, gaining aggressiveness and increasing expectancy of recurrence. The CD133 antigen is a pentaspan membrane glycoprotein, which has been proposed as a cancer stem cell marker, since it has been previously demonstrated to be capable of identifying a cancer initiating subpopulation in brain, colon, melanoma and other solid tumours. Therefore, our aim was to observe the possible presence of cells expressing the CD133 antigen within solid tumour cell lines of osteosarcoma and, then, understand their biological characteristics and performances.In this study, using SAOS2, MG63 and U2OS, three human sarcoma cell lines isolated from young Caucasian subjects, we were able to identify and characterize, among them, CD133+ cells showing the following features: high proliferation rate, cell cycle detection in a G2\M phase, positivity for Ki-67, and expression of ABCG2 transporters. In addition, at the FACS, we were able to observe the CD133+ cell fraction showing side population profile and forming sphere-clusters in serum-free medium with a high clonogenic efficiency.Taken together, our findings lead to the thought that we can assume that we have identified, for the first time, CD133+ cells within osteosarcoma cell lines, showing many features of cancer stem cells. This can be of rather interest in order to design new therapies against the bone cancer

Allelopathy of Bracken Fern (Pteridium arachnoideum): New Evidence from Green Fronds, Litter, and Soil

The neotropical bracken fern Pteridium arachnoideum (Kaulf.) Maxon. (Dennstaedtiaceae) is described as an aggressive pioneer plant species. It invades abandoned or newly burned areas and represents a management challenge at these invaded sites. Native to the Atlantic Forest and Cerrado (Tropical Savanna) Brazilian biomes, P. arachnoideum has nevertheless become very problematic in these conservation hotspots. Despite some reports suggesting a possible role of allelopathy in this plant’s dominance, until now there has been little evidence of isolated and individually identified compounds with phytotoxic activities present in its tissues or in the surrounding environment. Thus, the aim of this study was to investigate the allelopathic potential of P. arachnoideum by isolating and identifying any secondary metabolites with phytotoxic activity in its tissues, litter, and soil. Bioguided phytochemical investigation led to the isolation and identification of the proanthocyanidin selligueain A as the major secondary compound in the green fronds and litter of this fern. It is produced by P. arachnoideum in its green fronds, remains unaltered during the senescence process, and is the major secondary compound present in litter. Selligueain A showed phytotoxic activity against the selected target species sesame (Sesamum indicum) early development. In particular, the compound inhibited root and stem growth, and root metaxylem cell size but did not affect chlorophyll content. This compound can be considered as an allelochemical because it is present in the soil under P. arachnoideum patches as one of the major compounds in the soil solution. This is the first report of the presence of selligueain A in any member of the Dennstaedtiaceae family and the first time an isolated and identified allelochemical produced by members of the Pteridium species complex has been described. This evidence of selligueain A as a putative allelochemical of P. arachnoideum reinforces the role of allelopathy in the dominance processes of this plant in the areas where it occurs

Budget impact analysis of medicines : updated systematic review and implications

This evaluation determines whether published studies to date meet the key characteristics identified for budget impact analyses (BIA) for medicines, accomplished through a systematic review and assessment against identified key characteristics. Studies from 2001 to 2015 on "budget impact analysis" with "drug" interventions were assessed, selected based on their titles/abstracts and full texts, with their characteristics checked according to key criteria. Out of 1984 studies, 92 were identified. Of these, 95% were published in Europe and the USA. 2012 saw the largest number of publications (16%) with a decline thereafter. 48% met up to 6 or 7 out of the 9 key characteristics. Only 22% stated no conflict of interest. The results indicate low adherence to the key characteristics that should be considered for BIAs and strong conflict of interest. This is an issue since BIAs can be of fundamental importance in managing the entry of new medicines including reimbursement decisions

Satisfação no trabalho da equipe de enfermagem: revisão integrativa

Job satisfaction consists of a feeling of wellbeing, resulting from the interaction of several occupational aspects, and may influence the worker's relationship with the organization, clients and family. Hence, it becomes important for the quality of nursing care to reflect on this topic in depth. Therefore, this study aimed to examine the scientific evidence related to job satisfaction in Brazilian nursing. An integrative literature review was carried out in the databases LILACS, MEDLINE, BDENF and Cochrane Library, totaling 17 publications, categorized in: Job Satisfaction, Job Dissatisfaction and Associated Factors. It was concluded that job satisfaction is determined by a complex network of factors and may vary depending on the group studied. Additional research, particularly of evidence level III in different nursing fields, covering all of Brazil, is necessary to support the implementation of occupational improvements.La satisfacción en el trabajo consiste en un sentimiento de bienestar resultante de la interacción de varios aspectos ocupacionales, pudiendo influenciar la relación del trabajador con la organización, clientes y familia. Es importante para la calidad de la asistencia de enfermería realizar una reflexión profunda sobre este tema, por eso se objetivó en este estudio analizar las evidencias científicas referentes a la satisfacción en el trabajo del equipo de enfermería brasileño. Se trató de una revisión integradora de la literatura en las bases de datos LILACS, MEDLINE, BDENF y Biblioteca Cochrane, totalizando 17 publicaciones categorizadas en: Satisfacción en el Trabajo, Insatisfacción en el Trabajo y Factores Asociados. Se concluyó que la satisfacción en el trabajo es determinada por una red compleja de factores, pudiendo variar conforme el grupo estudiado. Investigaciones adicionales, especialmente con niveles de evidencias III, en diferentes campos de actuación de la enfermería, abarcando todo el Brasil, son necesarias para subsidiar la implantación de mejorías ocupacionales.A satisfação no trabalho consiste em sentimento de bem-estar. resultante da interação de vários aspectos ocupacionais, podendo influenciar a relação do trabalhador com a organização, clientes e família. Torna-se importante, para a qualidade da assistência de enfermagem, reflexão aprofundada sobre esse tema, e, por isso, objetivou-se neste estudo analisar as evidências científicas referentes à satisfação no trabalho da equipe de enfermagem brasileira. Trata-se de revisão integrativa da literatura nas bases de dados LILACS, MEDLINE, BDENF e Biblioteca Cochrane, totalizando 17 publicações categorizadas em: satisfação no trabalho, insatisfação no trabalho e fatores associados. Conclui-se que a satisfação no trabalho é determinada por rede complexa de fatores, podendo variar conforme o grupo estudado. Pesquisas adicionais, especialmente com níveis de evidências III, em diferentes campos de atuação da enfermagem, abrangendo todo Brasil, são necessárias para subsidiar a implantação de melhorias ocupacionais