Engineering functional kidney tissue using human iPS cells

Recent advances in the field of stem cell research have enabled the derivation of renal organoids from hiPSCs; these organoids might be a powerful tool with important implications for regenerative medicine, but meticulous assessment of the functional abilities of the induced nephrons is key to the use of these organoids in any application. Here, I show that hiPSC-derived renal organoids possess proximal tubular transporters and receptors; I present optimised techniques to assess the function of these receptors in-vitro and show that these organoids have anion and cation uptake capacities similar to what can be seen in foetal kidney tissue or isolated proximal tubules, implying tubular functional capacity, an aspect of renal physiology that has particular importance in the renal handling of drugs and toxins. Due to high blood flow and the primary role of the kidney in clearing toxins and metabolites, renal cells are highly vulnerable to drug toxicity. The lack of in-vitro high throughput models to screen pharmaceutical compounds for potential nephrotoxicity during drug development has always hindered the field of drug development and increased the cost of delivering drugs into the market; in this study, I demonstrate that hiPSCs-derived renal organoids are able to predict nephrotoxicity with reasonable accuracy. Combining this ability with the possibility of cryopreserving renal-differentiated cells and to the use of HMOX1 reporter cell line, to detect oxidative stress, could streamline the use of these organoids in nephrotoxicity screening and could potentially flourish the field of drug development. While the current model of renal organoids could be used for drug screening without further manipulation, the use of such tissue for therapeutic purposes necessitates a higher degree of organisation and complexity. In-vivo kidney function is based on the complex interplay of a range of highly specialised cells together with their three-dimensional structure and organisation. Scientists are adopting different strategies to build kidney tissue, from hiPSCs, that could be suitable for use in therapeutic applications. Common to any of these strategies is the need to generate the correct cell types in sufficient numbers and purity, and most important, in the right location. I aim in this study to isolate correctly differentiated ureteric bud (UB) structures from surrounding cells and to induce branching from single UB-like structure to recapitulate branching morphogenesis in-vitro. I conjugated GDNF protein to a fluorophore and used it to label the UB structures and isolate them. I show that the combination of GDNF, FGF1, CHIR99021 and RA was able to induce branching in the isolated UBlike structures. The ability to isolate pure differentiated UB structures from surrounding contaminant tissue and to induce them to branch forming contiguous collecting duct tree could be a step further towards engineering a more realistic kidney tissue with single continuous collecting duct system, yet optimising culture conditions and techniques to build such a tissue is still needed

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

"Hanging Rugs between Aesthetic Value of Flowers and Design Software"

The art of wall hanging textiles has become one of the highly valued artistic and aesthetic applied arts in civilized societies. It is an important method for decorating public buildings and houses, which covers a large areas of walls. The success of wall hanging rugs industry depends on the designer's ability on successful innovation in which he exploits his culture, imagination and skills in producing rugs characterized by beauty with performance efficiency, to access a high level of quality that impose their efficiency in the market competition. Design is considered one of the most important factors that helps to attract the customer and promote the product economically.Human use nature as a rich source of colors, lines and forms. It is rich in relations that correlate between elements in aesthetic expressive formations. The good artist is the one who has the ability to meditate the nature and distinguish the beauty in its relations. Many artists have created great artworks inspired by the simplest elements in nature such as flowers and plants of all kinds.With the entry of Egypt the free trade era, we had to look for methods to develop the rugs designs and enhance their aesthetic value through looking for a new source of design resources by natural flowers processing using design software such as Photoshop and Illustrator to produce authentic and innovative designs that provides the principles of a successful design such as diversity, balance, unity, rhythm. These designs will be implemented using hand-tufted carpets style.The research problem can be summarized in the predominance of the representative style in hanging rugs design derived from natural flowers and the need of presenting modern trends in the field of hanging rug designs.The research aims to get benefit of the design software in designing of hanging rugs from designs inspired by natural flowers.In this research, a group of hanging rug designs have been made by employing the design software to create designs inspired by natural flowers, and then implemented using the hand tuft

Mucosal Genes Expression in Inflammatory Bowel Disease Patients: New Insights

Individual differences in IBD illness severity, behavior, progression, and therapy response are evident. Since a break in the intestinal epithelial barrier causes IBD to begin, mucosal gene expression in IBD is crucial. Due to its high sensitivity and dynamic nature, molecular analysis of biomarkers in intestinal biopsies is feasible and provides a reliable means of evaluating localized inflammation. The goal of this investigation was to discover alterations in gene expression in the inflamed mucosa of IBD patients undergoing treatment with 5-amino salicylic acid (5ASA) (N = 39) or anti-TNF drugs (N = 22). The mucosal expression of numerous IBD-related genes was evaluated using qPCR. We discovered that the levels of the proteins Lipocalin-2 (LCN2), Nitric Oxide Synthase 2 (NOS2), Mucin 2 (MUC2), Mucin 5AC (MUC5AC), and Trefoil factor 1 (TFF1), which are overexpressed in untreated IBD patients compared to non-IBD subjects, are decreased by both therapy regimens. On the other hand, anti-TNF medicine helped the levels of ABCB1 and E-cadherin return to normal in IBD patients who were not receiving treatment