Medicine procurement and the use of flexibilities in the Agreement on Trade-Related Aspects of Intellectual Property Rights, 2001–2016

Millions of people, particularly in low- and middle-income countries, lack access to effective pharmaceuticals, often because they are unaffordable. The 2001 Ministerial Conference of the World Trade Organization (WTO) adopted the Doha Declaration on the TRIPS (Trade-Related Aspects of Intellectual Property Rights) Agreement and Public Health. The declaration recognized the implications of intellectual property rights for both new medicine development and the price of medicines. The declaration outlined measures, known as TRIPS flexibilities, that WTO Members can take to ensure access to medicines for all. These measures include compulsory licensing of medicines patents and the least-developed countries pharmaceutical transition measure. The aim of this study was to document the use of TRIPS flexibilities to access lower-priced generic medicines between 2001 and 2016. Overall, 176 instances of the possible use of TRIPS flexibilities by 89 countries were identified: 100 (56.8%) involved compulsory licences or public noncommercial use licences and 40 (22.7%) involved the least-developed countries pharmaceutical transition measure. The remainder were: 1 case of parallel importation; 3 research exceptions; and 32 non-patent-related measures. Of the 176 instances, 152 (86.4%) were implemented. They covered products for treating 14 different diseases. However, 137 (77.8%) concerned medicines for human immunodeficiency virus infection and acquired immune deficiency syndrome or related diseases. The use of TRIPS flexibilities was found to be more frequent than is commonly assumed. Given the problems faced by countries today in procuring high-priced, patented medicines, the practical, legal pathway provided by TRIPS flexibilities for accessing lower-cost generic equivalents is increasingly important

Extracellular Vesicles:Novel Opportunities to Understand and Detect Neoplastic Diseases

With a size range from 30 to 1000 nm, extracellular vesicles (EVs) are one of the smallest cell components able to transport biologically active molecules. They mediate intercellular communications and play a fundamental role in the maintenance of tissue homeostasis and pathogenesis in several types of diseases. In particular, EVs actively contribute to cancer initiation and progression, and there is emerging understanding of their role in creation of the metastatic niche. This fact underlies the recent exponential growth in EV research, which has improved our understanding of their specific roles in disease and their potential applications in diagnosis and therapy. EVs and their biomolecular cargo reflect the state of the diseased donor cells, and can be detected in body fluids and exploited as biomarkers in cancer and other diseases. Relatively few studies have been published on EVs in the veterinary field. This review provides an overview of the features and biology of EVs as well as recent developments in EV research including techniques for isolation and analysis, and will address the way in which the EVs released by diseased tissues can be studied and exploited in the field of veterinary pathology. Uniquely, this review emphasizes the important contribution that pathologists can make to the field of EV research: pathologists can help EV scientists in studying and confirming the role of EVs and their molecular cargo in diseased tissues and as biomarkers in liquid biopsies

Rationale, Design, and Baseline Characteristics of a Community-based Comparative Effectiveness Trial to Prevent Type 2 Diabetes in Economically Disadvantaged Adults: The RAPID Study

Reaching Out and Preventing Increases in Diabetes (RAPID) is a community-based randomized trial evaluating the comparative costs and effectiveness of a group-based adaption of the DPP lifestyle intervention developed and implemented in partnership with the YMCA. RAPID enrolled adult primary care patients, with BMI 24 kg/m2 or higher and abnormal glucose metabolism (HbA1c 5.7–6.9% or fasting plasma glucose 100–125 mg/dL). 509 participants were enrolled and randomized to one of two groups: standard clinical advice plus free-of-charge access to a group-based adaption of the DPP offered by the Y, versus standard clinical advice alone. Key outcomes for future analysis will include differences in body weight and other cardiovascular risk factors over a 24-month intervention period. At baseline, RAPID participants had a mean (SD) age of 51 ± 12.1 years, weight of 225.1 ± 56.2 lbs, and BMI of 36.9 ± 8.6 kg/m2. 70.7% were women, 57.2% were African American, 35.4% were non-Hispanic White, and 3.2% were Hispanic. Mean HbA1c was 6.05 ± 0.34%. Additionally, 55.4% of participants had a baseline systolic blood pressure of ≥ 130 mm Hg, 33.1% had a total blood cholesterol exceeding 200 mg/dL, and 74% reported a household income of < $25,000. The RAPID Study successfully randomized a large cohort of participants with a wide distribution of age, body weight, and race who are at high risk for developing type 2 diabetes

Економіко-правове забезпечення формування та реалізації соціальної політики держави, регіону, міста

У статті визначено потребу послідовного правового забезпечення формування та реалізації соціальної політики в багаторівневій системі управління. Обґрунтовано зміст та особливості соціальної політики залежно від рівня управління. Сформульовано пропозиції з удосконалення соціальної політики держави та її регіонів, виконано їх правову регламентацію

Identifying a gene expression signature of cluster headache in blood.

Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). Gene expression data were analysed by gene and by module of co-expressed genes with particular attention to previously implicated disease pathways including hypocretin dysregulation. Only moderate gene expression differences were identified and no associations were found with previously reported pathogenic mechanisms. At the level of functional gene sets, associations were observed for genes involved in several brain-related mechanisms such as GABA receptor function and voltage-gated channels. In addition, genes and modules of co-expressed genes showed a role for intracellular signalling cascades, mitochondria and inflammation. Although larger study samples may be required to identify the full range of involved pathways, these results indicate a role for mitochondria, intracellular signalling and inflammation in cluster headach

Пленум Наукової ради«Українська мова» Українська лексикографія та лексикологія: проблеми, завдання

10–11 листопада 2011року у Ніжинському державному університеты імені Миколи Гоголя відбувся Пленум Наукової ради “Українська мова” Інституту української мови НАН України на тему “Українська лексикографія та лексикологія: проблеми, завдання”

European Association of Urology and European Society for Paediatric Urology Guidelines on Paediatric Urinary Stone Disease

Context: Paediatric stone disease is an important clinically entity and management is often challenging. Although it is known that the condition is endemic in some geographic regions of the world, the global incidence is also increasing. Patient age and sex; the number, size, location, and composition of the stone; and the anatomy of the urinary tract are factors that need to be taken into consideration when choosing a treatment modality. Objective: To provide a general insight into the evaluation and management of urolithiasis in the paediatric population in the era of minimally invasive surgery. Evidence acquisition: A nonsystematic review of the literature on management of paediatric urolithiasis was conducted with the aim of presenting the most suitable treatment modality for different scenarios. Evidence synthesis: Because of high recurrence rates, open surgical intervention is not the first option for paediatric stone disease, except for very young patients with very large stones in association with congenital abnormalities. Minimally invasive surgeries have become the first option with the availability of appropriately sized instruments and accumulating experience. Extracorporeal shockwave lithotripsy (SWL) is noninvasive and can be carried out as an outpatient procedure under sedation, and is the initial choice for management of smaller stones. However, for larger stones, SWL has lower stone-free rates and higher retreatment rates, so minimally invasive endourology procedures such as percutaneous nephrolithotomy and retrograde intrarenal surgery are preferred treatment options. Conclusions: Contemporary surgical treatment for paediatric urolithiasis typically uses minimally invasive modalities. Open surgery is very rarely indicated. Patient summary: Cases of urinary stones in children are increasing. Minimally invasive surgery can achieve high stone-free rates with low complication rates. After stone removal, metabolic evaluation is strongly recommended so that medical treatment for any underlying metabolic abnormality can be given. Regular follow-up with imaging such as ultrasound is required because of the high recurrence rates