Formulation and Characterization of Phytostanol Ester Solid Lipid Nanoparticles for the Management of Hypercholesterolemia: An ex vivo Study.

Background: Phytostanols are naturally occurring compounds that reduce blood cholesterol levels significantly. However, their aqueous insolubility poses formulation challenges. Aim: To formulate and characterize solid lipid nanoparticle carriers for phytostanol esters to enhance the bioavailability of phytostanols. Methods: Phytostanol ester solid lipid nanoparticles were formulated by the microemulsion method. They were characterized for particle size distribution, polydispersity index, shape, surface charge, entrapment efficiency, stability, chemical structure, and thermal properties. The uptake of the formulation by cell lines, HepG2 and HT-29, and its effect on cell viability were evaluated. Results: The formulation of solid lipid nanoparticles was successfully optimised by varying the type of lipids and their concentration relative to that of surfactants in the present study. The optimised formulation had an average diameter of (171 ± 9) nm, a negative surface charge of (− 23.0 ± 0.8) mV and was generally spherical in shape. We report high levels of drug entrapment at (89 ± 5)% in amorphous form, drug loading of (9.1 ± 0.5)%, nanoparticle yield of (67 ± 4)% and drug excipient compatibility. The biological safety and uptake of the formulations were demonstrated on hepatic and intestinal cell lines. Conclusion: Phytostanol ester solid lipid nanoparticles were successfully formulated and characterized. The formulation has the potential to provide an innovative drug delivery system for phytostanols which reduce cholesterol and have a potentially ideal safety profile. This can contribute to better management of one of the main risk factors of cardiovascular disease

Development of an international scale of socio-economic position based on household assets.

The importance of studying associations between socio-economic position and health has often been highlighted. Previous studies have linked the prevalence and severity of lung disease with national wealth and with socio-economic position within some countries but there has been no systematic evaluation of the association between lung function and poverty at the individual level on a global scale. The BOLD study has collected data on lung function for individuals in a wide range of countries, however a barrier to relating this to personal socio-economic position is the need for a suitable measure to compare individuals within and between countries. In this paper we test a method for assessing socio-economic position based on the scalability of a set of durable assets (Mokken scaling), and compare its usefulness across countries of varying gross national income per capita.Ten out of 15 candidate asset questions included in the questionnaire were found to form a Mokken type scale closely associated with GNI per capita (Spearmans rank rs = 0.91, p = 0.002). The same set of assets conformed to a scale in 7 out of the 8 countries, the remaining country being Saudi Arabia where most respondents owned most of the assets. There was good consistency in the rank ordering of ownership of the assets in the different countries (Cronbachs alpha = 0.96). Scores on the Mokken scale were highly correlated with scores developed using principal component analysis (rs = 0.977).Mokken scaling is a potentially valuable tool for uncovering links between disease and socio-economic position within and between countries. It provides an alternative to currently used methods such as principal component analysis for combining personal asset data to give an indication of individuals relative wealth. Relative strengths of the Mokken scale method were considered to be ease of interpretation, adaptability for comparison with other datasets, and reliability of imputation for even quite large proportions of missing values

The Role of Cyclo(His-Pro) in Neurodegeneration

Neurodegenerative diseases may have distinct genetic etiologies and pathological manifestations, yet share common cellular mechanisms underpinning neuronal damage and dysfunction. These cellular mechanisms include excitotoxicity, calcium dysregulation, oxidative damage, ER stress and neuroinflammation. Recent data have identified a dual role in these events for glial cells, such as microglia and astrocytes, which are able both to induce and to protect against damage induced by diverse stresses. Cyclo(His-Pro), a cyclic dipeptide derived from the hydrolytic removal of the amino-terminal pyroglutamic acid residue of the hypothalamic thyrotropin-releasing hormone, may be important in regulating the nature of the glial cell contribution. Cyclo(His-Pro) is ubiquitous in the central nervous system and is a key substrate of organic cation transporters, which are strongly linked to neuroprotection. The cyclic dipeptide can also cross the brain-blood-barrier and, once in the brain, can affect diverse inflammatory and stress responses by modifying the Nrf2-NF-B signaling axis. For these reasons, cyclo(His-Pro) has striking potential for therapeutic application by both parenteral and oral administration routes and may represent an important new tool in counteracting neuroinflammation-based degenerative pathologies. In this review, we discuss the chemistry and biology of cyclo(His-Pro), how it may interact with the biological mechanisms driving neurodegenerative disease, such as amyotrophic lateral sclerosis, and thereby act to preserve or restore neuronal function

Age- and sex-related variations in platelet count in Italy: a proposal of reference ranges based on 40987 subjects' data

BACKGROUND AND OBJECTIVES: Although several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150-400×10(9) platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count. METHODS: We analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles. RESULTS: Platelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×10(9)/L in children (176-452), adult men (141-362), adult women (156-405), old men (122-350) and, old women (140-379). Moreover, we calculated an extended reference interval that takes into account the differences in platelet count observed in different geographic areas. CONCLUSIONS: The age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy

El panorama educativo de la era digital: prácticas comunicativas que (nos) impulsan hacia adelante

En este artículo, se identificarán algunos modelos y tendencias emergentes en la producción de conocimiento. Se hará hincapié especialmente en cómo los individuos implicados en los procesos de consumo y de distribución de la información expresan diferentes niveles de solidaridad y de compromiso, y se sugerirá que es crucial que las personas no solo conozcan estos procesos, sino que también estén abiertas a otros modelos, oportunidades y posibilidades que, dadas las condiciones sociotecnológicas y comunicativas actuales, aún deben desarrollarse. Se abordará con especial interés el ámbito de la educación, puesto que se entiende que los educadores están participando de forma comprometida en una profunda renovación pedagógica a través de proyectos compartidos cimentados en interacciones profesionales y personales facilitadas por las redes. Estas interacciones favorecen la emergencia de modelos pedagógicos que permiten a profesores y a alumnos convertirse en expertos al mismo tiempo que rompen con muchas convenciones epistemológicas clásicas. Estas pedagogías generadas de abajo arriba no solo fomentan la creatividad y la colaboración, y se sustentan en el uso de nuevas herramientas digitales, sino que las promueven e impulsan los intereses del alumnado, y por ello, tienen el potencial suficiente para devolverle la alegría al proceso de aprendizaje. Por último, se argumentará que los modelos emergentes en la construcción del conocimiento a través de las TIC ofrecen nuevos paisajes culturales y ecologías de aprendizaje que trastocan las inscripciones tradicionales de las identidades individuales y las afinidades raciales y culturales.This paper identifies trends in the emerging models of knowledge production available in our society. We suggest it is crucial not only to be aware of these emerging models but also to be open to opportunities and possibilities that may still develop. We consider how people may express different levels of solidarity and commitment to these trends and models in their information consumption and distribution processes. We discuss how educators are now engaging in profound pedagogical renewal by expressing deeper levels of solidarity and commitment to knowledge production and educational projects through professional and personal interactions. These interactions are producing pedagogical models that allow both teachers and learners to become knowledgeable while simultaneously breaking away from domain conventions. These bottom-up pedagogies foster creativity, collaboration and the use of new digital tools. They are driven by learner interests and, as such, have the potential to bring the joy back into the learning process. Finally, we argue that emerging models of knowledge construction mediated by ICT provide new cultural landscapes and ecologies of learning that disrupt traditional inscriptions of individual identities and racial-cultural affinities

The health impact of hazardous waste landfills and illegal dumps contaminated sites: An epidemiological study at ecological level in Italian Region

Background and aim: The implementation of idoneous management of hazardous waste, in contrast to illegal practices, is one of the environment and health priorities of the WHO. The aim of the present study, based on a collaborative agreement between the Italian National Health Institute and a Prosecution Office located in Naples North, was to evaluate the health effects of illegal landfills and burning of urban and hazardous waste in the territory of the Prosecution Office. Methods: The municipalities included in the study territory were investigated with respect to the regional population. Regression analyses were performed in the study area between four classes of an environmental municipal indicator of waste risk (MRI) previously defined, computing the relative risks (RRs) in 2–4 MRI classes, with respect to the first MRI class (the least impacted). The prevalence of reproductive outcomes and cause-specific mortality and hospitalization were analyzed in the general population and in the 0–19-year-old population using SAS software. Results: An increase of mortality and hospitalization risk in both the genders of the whole area, with respect to regional population, were found for overall all cancer cases, cancer of the stomach, the liver, the lung and the kidney, and ischemic heart diseases. An increase of mortality for leukemias in the 0-19-year-old population and in hospitalization risk for certain conditions originating in the perinatal period were observed. Correlation between MRI and the risk of mortality from breast tumors in women (MRI class 2: RR = 1.06; MRI class 3: RR = 1.15; MRI class 4: RR = 1.11) and between MRI and the risk of hospitalization from testis tumors (MRI class 2: RR = 1.25; MRI class 3: RR = 1.31; MRI class 4: RR = 1.32) were found. The hospitalization risk from breast tumors and asthma exceeded significantly in both genders of three and four MRI classes. Among the 0-19-year-old population, correlation between MRI and hospitalization from leukemias (MRI class 2: RR = 1.48; MRI class 3: RR = 1.60; MRI class 4: RR = 1.41) and between MRI and the prevalence of preterm birth (MRI class 2: RR = 1.17; MRI class 3: RR = 1.08; MRI class 4: RR = 1.25) were found. Conclusion: A correlation between health outcomes and the environmental pressure by uncontrolled waste sites was found. Notwithstanding the limitation of the study, the results promote implementing the actions of environmental remediation and the prosecution of illegal practices

Weak localization competes with the quantum oscillations in a natural electronic superlattice: the case of Na1.5(PO2)4(WO3)20

We report an investigation of the combined structural and electronic properties of the bronze Na1.5 (PO2 )4 (WO3 )20 . Its low-dimensional structure and possible large reconstruction of the Fermi surface due to charge density wave instability make this bulk material a natural superlattice with a reduced number of carriers and Fermi energy. Signatures of multilayered two-dimensional (2D) electron weak localization are consequently reported, with an enhanced influence of quantum oscillations. A crossover between these two antagonistic entities, previously observed only in genuine low-dimensional materials and devices, is shown to occur in a bulk crystal due to its hidden 2D nature

Case Report: Heterozygous Germline Variant in EIF6 Additional to Biallelic SBDS Pathogenic Variants in a Patient With Ribosomopathy Shwachman–Diamond Syndrome

Background: Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive ribosomopathy mainly characterized by exocrine pancreatic insufficiency, skeletal alterations, neutropenia, and a relevant risk of hematological transformation. At least 90% of SDS patients have pathogenic variants in SBDS, the first gene associated with the disease with very low allelic heterogeneity; three variants, derived from events of genetic conversion between SBDS and its pseudogene, SBDSP1, provided the alleles observed in about 62% of SDS patients.Methods: We performed a reanalysis of the available WES files of a group of SDS patients with biallelic SBDS pathogenic variants, studying the results by next bioinformatic and protein structural analysis. Parallelly, careful clinical attention was given to the patient focused in this study.Results: We found and confirmed in one SDS patient a germline heterozygous missense variant (c.100T>C; p.Phe34Leu) in the EIF6 gene. This variant, inherited from his mother, has a very low frequency, and it is predicted as pathogenic, according to several in silico prediction tools. The protein structural analysis also envisages the variant could reduce the binding to the nascent 60S ribosomal.Conclusion: This study focused on the hypothesis that the EIF6 germline variant mimics the effect of somatic deletions of chromosome 20, always including the locus of this gene, and similarly may rescue the ribosomal stress and ribosomal dysfunction due to SBDS mutations. It is likely that this rescue may contribute to the stable and not severe hematological status of the proband, but a definite answer on the role of this EIF6 variant can be obtained only by adding a functional layer of evidence. In the future, these results are likely to be useful for selected cases in personalized medicine and therapy

Grounding knowledge and normative valuation in agent-based action and scientific commitment

Philosophical investigation in synthetic biology has focused on the knowledge-seeking questions pursued, the kind of engineering techniques used, and on the ethical impact of the products produced. However, little work has been done to investigate the processes by which these epistemological, metaphysical, and ethical forms of inquiry arise in the course of synthetic biology research. An attempt at this work relying on a particular area of synthetic biology will be the aim of this chapter. I focus on the reengineering of metabolic pathways through the manipulation and construction of small DNA-based devices and systems synthetic biology. Rather than focusing on the engineered products or ethical principles that result, I will investigate the processes by which these arise. As such, the attention will be directed to the activities of practitioners, their manipulation of tools, and the use they make of techniques to construct new metabolic devices. Using a science-in-practice approach, I investigate problems at the intersection of science, philosophy of science, and sociology of science. I consider how practitioners within this area of synthetic biology reconfigure biological understanding and ethical categories through active modelling and manipulation of known functional parts, biological pathways for use in the design of microbial machines to solve problems in medicine, technology, and the environment. We might describe this kind of problem-solving as relying on what Helen Longino referred to as “social cognition” or the type of scientific work done within what Hasok Chang calls “systems of practice”. My aim in this chapter will be to investigate the relationship that holds between systems of practice within metabolic engineering research and social cognition. I will attempt to show how knowledge and normative valuation are generated from this particular network of practitioners. In doing so, I suggest that the social nature of scientific inquiry is ineliminable to both knowledge acquisition and ethical evaluations