The Scenario for Constructing Flexible, People Focused Systems Development Methodologies

Systems development is a very complex process, which requires disciplined methodological approaches. While there are many arguments underpinning the use of systems development methodologies empirical investigations show that methodologies are underused in practice and what is more their use is not on the increase. In this paper we discuss the usage of agile methodologies which tend to be more people-focused and adaptable to project-specific circumstances. We believe that usage of such methodologies may encourage practitioners to rank the methodologies higher in terms of their contributions to successful development. In the paper we propose a scenario for development, introduction and maintenance of an agile methodology in an organisation

Pancreas Physiology

In the exocrine pancreas, the relationship between structure and function, as well as between normal and pathological functioning, can be easily understood if presented in a systematic and logical manner. In this chapter, we explain pancreas physiology. We start by explaining the embryological and ontogenetic development of the pancreas and describe the basic anatomical characteristics of the mature gland, i.e. the macro- and microscopic structure, its vascular supply and innervation. These form the foundation necessary to understand the mechanisms of acinar and ductal cell secretion and their regulation, which are covered in the middle part, with an emphasis on the ionic part of the pancreatic juice. In the last part, we focus on the enzymatic part of the pancreatic juice and its role in digestion of all main groups of energy-rich nutrients, i.e. carbohydrates, proteins and lipids. Two main sources of additional information will help the reader grasp the main concepts in pancreas physiology: figures summarize and combine various concepts encountered in the main text, and clinical boxes contain examples of how a given piece of knowledge can be relevant to understand some diseases

Single-cell analysis reveals IGF-1 potentiation of inhibition of the TGF-ß/Smad pathway of fibrosis in human keratocytes in vitro

Corneal wound healing is often affected by TGF-β–mediated fibrosis and scar formation. Guided fibrosis with IGF-1 and antifibrotic substances might maintain corneal transparency. Primary human corneal keratocytes under serum-free conditions were used as a model of corneal stromal wounding, with markers of corneal fibrosis and opacity studied under TGF-β2 stimulation. Single-cell imaging flow cytometry was used to determine nuclearization of Smad3, and intracellular fluorescence intensity of Smad7 and the corneal crystallin aldehyde dehydrogenase 3A1. Extracellular matrix proteoglycans keratocan and biglycan were quantified using ELISAs. On the TGF-β2 background, the keratocytes were treated with IGF-1, and suberoylanilidehydroxamic acid (SAHA) or halofuginone ± IGF-1. IGF-1 alone decreased Smad3 nuclearization and increased aldehyde dehydrogenase 3A1 expression, with favorable extracellular matrix proteoglycan composition. SAHA induced higher Smad7 levels and inhibited translocation of Smad3 to the nucleus, also when combined with IGF-1. Immunofluorescence showed that myofibroblast transdifferentiation is attenuated and appearance of fibroblasts is favored by IGF-1 alone and in combination with the antifibrotic substances. The TGF-β/Smad pathway of fibrosis and opacity was inhibited by IGF-1, and further with SAHA in particular, and with halofuginone. IGF-1 is thus a valid aid to antifibrotic treatment, with potential for effective and transparent corneal wound healing

Platelet-rich plasma, especially when combined with a TGF-ß inhibitor promotes proliferation, viability and myogenic differentiation of myoblasts in vitro

Regeneration of skeletal muscle after injury is limited by scar formation, slow healing time and a high recurrence rate. A therapy based on platelet-rich plasma (PRP) has become a promising lead for tendon and ligament injuries in recent years, however concerns have been raised that PRP-derived TGF-β could contribute to fibrotic remodelling in skeletal muscle after injury. Due to the lack of scientific grounds for a PRP -based muscle regeneration therapy, we have designed a study using human myogenic progenitors and evaluated the potential of PRP alone and in combination with decorin (a TGF-β inhibitor), to alter myoblast proliferation, metabolic activity, cytokine profile and expression of myogenic regulatory factors (MRFs). Advanced imaging multicolor single-cell analysis enabled us to create a valuable picture on the ratio of quiescent, activated and terminally committed myoblasts in treated versus control cell populations. Finally high-resolution confocal microscopy validated the potential of PRP and decorin to stimulate the formation of polynucleated myotubules. PRP was shown to down-regulate fibrotic cytokines, increase cell viability and proliferation, enhance the expression of MRFs, and contribute to a significant myogenic shift during differentiation. When combined with decorin further synergistc effects were identified. These results suggest that PRP could not only prevent fibrosis but could also stimulate muscle commitment, especially when combined with a TGF-β inhibitor

COVID-19. Pandemic surgery guidance

Abstract – Based on high quality surgery and scientific data, scientists and surgeons are committed to protecting patients as well as healthcare staff and hereby provide this Guidance to address the special issues circumstances related to the exponential spread of the Coronavirus disease 2019 (COVID-19) during this pandemic. As a basis, the authors used the British Intercollegiate General Surgery Guidance as well as recommendations from the USA, Asia, and Italy. The aim is to take responsibility and to provide guidance for surgery during the COVID-19 crisis in a simplified way addressing the practice of surgery, healthcare staff and patient safety and care. It is the responsibility of scientists and the surgical team to specify what is needed for the protection of patients and the affiliated healthcare team. During crises, such as the COVID-19 pandemic, the responsibility and duty to provide the necessary resources such as filters, Personal Protective Equipment (PPE) consisting of gloves, fluid resistant (Type IIR) surgical face masks (FRSM), filtering face pieces, class 3 (FFP3 masks), face shields and gowns (plastic ponchos), is typically left up to the hospital administration and government. Various scientists and clinicians from disparate specialties provided a Pandemic Surgery Guidance for surgical procedures by distinct surgical disciplines such as numerous cancer surgery disciplines, cardiothoracic surgery, ENT, eye, dermatology, emergency, endocrine surgery, general surgery, gynecology, neurosurgery, orthopedics, pediatric surgery, reconstructive and plastic surgery, surgical critical care, transplantation surgery, trauma surgery and urology, performing different surgeries, as well as laparoscopy, thoracoscopy and endoscopy. Any suggestions and corrections from colleagues will be very welcome as we are all involved and locked in a rapidly evolving process on increasing COVID-19 knowledg

Intracellular Serotonin Modulates Insulin Secretion from Pancreatic β-Cells by Protein Serotonylation

Non-neuronal, peripheral serotonin deficiency causes diabetes mellitus and identifies an intracellular role for serotonin in the regulation of insulin secretion

Fiziologija ledvic

Pričujoči prispevek opisuje, kako ledvice delujejo v normalnih razmerah. Poudarek je na opisu pretoka snovi skozi ledvice, predvsem soli, vode in nekaterih proizvodov presnove. Podrobneje so prikazani in razloženi ledvični klirens in protitočni sistemi, pomembni pri tvorbi seča in gospodarjenjem z vodo.These chapter describes the normal kidney function. The emphasis is on the mass flow of salts, water and some other products of the metabolism through the kidney tubular system. The clirens and counter-current flow systems and their function in the urin formation and the household of water are outlined