The System of Modern Social Work with Children with Disabilities in the Context of Neuropedagogy: Traditions and Innovations

The article deals with the interaction of sociology, in particular the practice of social work, with neuropedagogy and neuropsychology; The main political, legal and pedagogical principles of neuropedagogy of disability are outlined. Taking into account the new inclusive paradigm of disability, modern social, pedagogical and psychological approaches to accompanying children with special needs, the points of intersection of neuropsychology with other socio-humanitarian disciplinesю There is also a brief digression into the formation of neuropedagogy as a science, the classical principles that formed its basis and the main achievements in modern times (since the 70's of the twentieth century). The article identifies and compares a set of psychophysiological and social problems of children with disabilities, which can be solved by the integrated use of social support and neuropedagogy. The expediency of development and implementation of scientific results of the newest interdisciplinary field - neurosociology is substantiated. During the research, methods relevant for theoretical works were used - historical excursion, analysis of theoretical material, generalization, comparison, interdisciplinary extrapolation. The discussion revealed that the patterns obtained during the study of traditions and innovations in the system of social work and neuropedagogical support are currently relevant and widely analyzed in scientific discourse: in sociology, pedagogy, psychology, defectology, correction, rehabilitation and medicine. It is established that the prospect of further research is a constructive synthesis of the above disciplines in the field of neurosociology with the development and delineation of a universal categorical apparatus and methodological and diagnostic tools.</em

Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines

There has been an escalating interest in the medicinal use of Cannabis sativa in recent years. Cannabis is often administered orally with fat-containing foods, or in lipid-based pharmaceutical preparations. However, the impact of lipids on the exposure of patients to cannabis components has not been explored. Therefore, the aim of this study is to elucidate the effect of oral co-administration of lipids on the exposure to two main active cannabinoids, ?9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In this study, oral co-administration of lipids enhanced the systemic exposure of rats to THC and CBD by 2.5-fold and 3-fold, respectively, compared to lipid-free formulations. In vitro lipolysis was conducted to explore the effect of lipids on the intestinal solubilisation of cannabinoids. More than 30% of THC and CBD were distributed into micellar fraction following lipolysis, suggesting that at least one-third of the administered dose will be available for absorption following co-administration with lipids. Both cannabinoids showed very high affinity for artificial CM-like particles, as well as for rat and human CM, suggesting high potential for intestinal lymphatic transport. Moreover, comparable affinity of cannabinoids for rat and human CM suggests that similar increased exposure effects may be expected in humans. In conclusion, co-administration of dietary lipids or pharmaceutical lipid excipients has the potential to substantially increase the exposure to orally administered cannabis and cannabis-based medicines. The increase in patient exposure to cannabinoids is of high clinical importance as it could affect the therapeutic effect, but also toxicity, of orally administered cannabis or cannabis-based medicines

Discovery and Development of Toll-Like Receptor 4 (TLR4) Antagonists: A New Paradigm for Treating Sepsis and Other Diseases

Abstract. Sepsis remains the most common cause of death in intensive care units in the USA, with a current estimate of at least 750,000 cases per year, and 215,000 deaths annually. Despite extensive research still we do not quite understand the cellular and molecular mechanisms that are involved in triggering and propagation of septic injury. Endotoxin (lipopolysaccharide from Gram-negative bacteria, or LPS) has been implicated as a major cause of this syndrome. Inflammatory shock as a consequence of LPS release remains a serious clinical concern. In humans, inflammatory responses to LPS result in the release of cytokines and other cell mediators from monocytes and macrophages, which can cause fever, shock, organ failure and death. A number of different approaches have been investigated to try to treat and/or prevent the septic shock associated with infections caused by Gram-negative bacteria, including blockage of one or more of the cytokines induced by LPS. Recently several novel amphipathic compounds have been developed as direct LPS antagonists at the LPS receptor, TLR4. This review article will outline the current knowledge on the TLR4-LPS synthesis and discuss the signaling, in vitro pre-clinical and in vivo clinical evaluation of TLR4 antagonists and their potential use in sepsis and a variety of diseases such as atherosclerosis as well as hepatic and renal malfunction. KEY WORDS: drug discovery; LPS; sepsis; toll-like receptor antagonists

Caracteres socioculturales y artísticos de los Sikuris como tradición en la Festividad Virgen de la Candelaria Puno – 2015

TesisLa presente investigación estudia las caracteres socioculturales y artísticas de los sikuris como tradición en la festividad Virgen de la Candelaria de Puno, investigación realizada durante el año 2015. La festividad de la Virgen de la Candelaria de Puno es una ceremonia religiosidad y ritual más importante del sur peruano y uno de los espacios más significativos que expresan el sincretismo festivo y ritual de América Latina. La metodología de investigación es de tipo cualitativo y diseño etnográfico e histórico, la técnica utilizada de la investigación es la observación participante, entrevista y biblioteca a cual está sustentada en base a documentos históricos de fuentes primarias y secundarias, que contribuyen al estudio de la historia de la cultura andina. El objetivo general formulado busca describir las características socioculturales y artísticas de los sikuris como tradición en la Festividad Virgen de la Candelaria Puno-2015. Según los resultados de la investigación se establece que las características del sikuris es una manifestación ancestral andina altiplánica peruana, que se practica actualmente en la festividad de la Virgen Candelaria de Puno, es de carácter sociocultural porque es una expresión heredada, que se practica colectivamente, tiene fines rituales, perdura en la comunidad andina y es una manifestación artística ya que tiene una organización adecuada en cuanto a sus instrumentos, vestuarios y coreografía que dan una muestra de gran expresión artística utilizando principalmente el Siku, que es un instrumento de música de viento de la cultura andina de origen ancestral, cultivada por diversas culturas pre- inkas e inka del pasado histórico peruano, su carácter más esencial es el dualismo y el colectivism

Targeting Neuronal Transcription Factor BRN2 in Neuroendocrine Tumors

No targeted therapies exist against aggressive neuroendocrine tumors; hence, these patients are limited to platinum-based chemotherapy that has not advanced in over three decades. [...]Medicine, Faculty ofOther UBCUrologic Sciences, Department ofReviewedFacult

The Effect of Digestion and Drug Load on Halofantrine Absorption from Self-nanoemulsifying Drug Delivery System (SNEDDS)

A super-saturated self-nanoemulsifying drug delivery system (super-SNEDDS), containing the poorly water-soluble drug halofantrine (Hf) at 150% of equilibrium solubility (S eq), was compared in vitro and in vivo with a conventional SNEDDS (75% of S eq) with respect to bioavailability and digestibility. Further, the effect of digestion on oral absorption of Hf from SNEDDS and super-SNEDDS was assessed by incorporation of the lipase inhibitor tetrahydrolipstatin (orlistat) into the SNEDDS. The SNEDDS contained soybean oil/Maisine 34-I (1:1), Kolliphor RH40, and ethanol at a ratio of 55:35:10, w/w percent. For the dynamic in vitro lipolysis, the precipitation of Hf at 60 min was significantly larger for the super-SNEDDS (66.8 ± 16.4%) than for the SNEDDS (18.5 ± 9.2%). The inhibition of the in vitro digestion by orlistat (1% (w/w)) lowered drug precipitation significantly for both the super-SNEDDS (36.8 ± 1.7%) and the SNEDDS (3.9 ± 0.7%). In the in vivo studies, the super-SNEDDS concept proved valid in a rat model with a significantly larger C max for the super-SNEDDS (964 ± 167 ng/mL) than for the SNEDDS (506 ± 112 ng/mL). The bioavailability of Hf dosed in super-SNEDDS (32.9 ± 3.6%) and SNEDDS (22.5 ± 6.3%) did not change significantly with co-administration of orlistat (45.5 ± 7.3% and 21.9 ± 6.5%, respectively). However, the pharmacokinetic parameters changed; the t max of the super-SNEDDS (1.3 ± 0.1 h) and SNEDDS (2.8 ± 1.2 h) were significantly lower when dosed with orlistat (6.0 ± 1.3 and 6.3 ± 1.2 h, respectively). These findings suggest that the role of lipid digestion for the absorption of drugs from SNEDDS may be less important than previously thought.Maria Høtoft Michaelsen, Kishor M. Wasan, Olena Sivak, Anette Müllertz, Thomas Rade

Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet

The aim of this work was to assess the effect of chronic administration of protonated nanostructured aluminosilicate (NSAS) on the plasma cholesterol levels and development of atherosclerotic lesions in Apolipoprotein (ApoE) deficient mice fed a high cholesterol and high fat diet. Apolipoprotein E (ApoE) deficient mice were divided into the following treatment groups: protonated NSAS 1.4% (w/w), untreated control and 2% (w/w) stigmastanol mixed with high-cholesterol/high-fat diet. Animals were treated for 12 weeks, blood samples were withdrawn every 4 weeks for determination of plasma cholesterol and triglyceride levels. At the end of the study the aortic roots were harvested for assessment of atherosclerotic lesions. NSAS at 1.4% (w/w) and stigmastanol at 2% (w/w) treatment groups showed significant decreases in plasma cholesterol concentrations at all time points relative to the control animals. The lesion sum area in 1.4% (w/w) NSAS and 2% (w/w) stigmastanol groups were significantly less from the control animals. In conclusion, in this study, the effectiveness of chronic administration of protonated NSAS material in the reduction of plasma cholesterol levels and decrease in development of atherosclerotic lesions was demonstrated in Apo-E deficient mice model.Pharmaceutical Sciences, Faculty ofNon UBCReviewedFacult

Efficacy of Postnatal In Vivo Nonsense Suppression Therapy in a Pax6 Mouse Model of Aniridia

Nonsense mutations leading to premature stop codons are common occurring in approximately 12% of all human genetic diseases. Thus, pharmacological nonsense mutation suppression strategies would be beneficial to a large number of patients if the drugs could be targeted to the affected tissues at the appropriate time. Here, we used nonsense suppression to manipulate Pax6 dosage at different developmental times in the eye of the small eye (Pax6Sey/+; G194X) mouse model of aniridia. Efficacy was assessed by functional assays for visual capacity, including electroretinography and optokinetic tracking (OKT), in addition to histological and biochemical studies. Malformation defects in the Pax6Sey/+ postnatal eye responded to topically delivered nonsense suppression in a dose- and time-dependent manner. Elevated levels of Mmp9, a direct downstream target of Pax6 in the cornea, were observed with the different treatment regimens. The lens capsule was particularly sensitive to Pax6 dosage, revealing a potential new role for Pax6 in lens capsule maintenance and development. The remarkable capacity of malformed ocular tissue to respond postnatally to Pax6 dosage in vivo demonstrates that the use of nonsense suppression could be a valuable therapeutic approach for blinding diseases caused by nonsense mutations