Renal engineering:strategies to address the problem of the ureter

Current techniques for making renal organoids generate tissues that show function when transplanted into a host, but they have no ureter through which urine can drain. There are at least 4 possible strategies for adding a ureter: connecting to ta host ureter; inducing an engineered kidney to make a ureter; making a stem-cell derived ureter; and replacement of only damaged cortex and outer medulla, using remaining host calyces, pelvis and ureter. Here we review progress: local BMP4 can induce a collecting duct tubule to become a ureter; a urothelial tube can be produced directly from pluripotent cells, and connect to the collecting duct system of a renal organoid; it is possible to graft ES cell-derived ureters into host kidney rudiments and see connection, smooth muscle development and spontaneous contraction, but this has not yet been achieved with all components being derived from ES cells. Remaining problems are discussed

INTERFERON-ALPHA SIGNALING PATHWAY IN THE SENSORY AUDITORY NEUROEPITHELIAL CELLS

The current study investigated the effect of interferon-á (IFN-á) on the cochlear cell line to shed light on the mechanisms by which interferon alpha may affect hearing. HEI-OC1 cell line and real time-PCR were used to determine the expression of those genes that might be involved in these mechanisms. Dose- (20, 40, & 80 U/ml) and time-dependent experiment-1 did not show significant alteration in gene expression associated with the stimulations of the IFN-á receptors. Therefore, a second experiment was planned. A 3 X 4 factorial design, consisting of three treatment conditions (0, 200 & 2000U/ml) and four time-points (6, 12, 24 & 48 Hrs), was employed. The results of experiment-2 revealed that significant differential expression of inflammatory genes, immune response genes and apoptotic genes is found in a dose- and time-dependent manner. This outcome indicates that IFN-á treatment led to initiation of an inflammatory response, an immune response and apoptosis of the cochlear cells, which was confirmed by a reduction in cell viability. The immune response was the most pronounced response; whereas inflammatory the apoptotic responses were transient. Therefore, the current in-vitro study indicates that the inflammatory response, the immune response and apoptosis might be the underlying mechanisms involved in the hearing impairment previously reported in patients under IFN-á therapy. These results imply that pre-treatment hearing evaluation as well as close monitoring of hearing function in patients undergoing long-term high-dose of IFN-á therapy are necessary to avoid or to minimize its adverse effect on hearing. The results also indicate that there is a need for further investigation of other markers that might be involved in signaling pathways of IFN-á, including markers for intrinsic pathway of apoptosis and antiapoptotic markers as well as markers for necrosis. This information might open an avenue for therapeutic intervention that can protect the inner ear from the ototoxic effect of some medications in general and IFN-á in particular and treat some immune-mediated inner ear disorders. In addition, this information might help in identifying novel diagnostic markers for vulnerability, severity, and outcomes of any cochlear pathology

Simulasi Tampungan Bendung Gerak Sembayat Sebagai Longstorage Untuk Pemenuhan Kebutuhan Air Baku Dan Irigasi Di Kabupaten Lamongan Dan Wilayah Utara Kabupaten Gresik

Bendung Gerak Sembayat (BGS) terletak di Desa Sragen, Kecamatan Bungah, Gresik sekitar 29 km dari arah hilir sungai Bengawan Solo hulu hilir. Luas waduk BGS adalah dari Babat sampai ke Sembayat Barrage ± 1487 km2. DAS Bengawan Solo keadaan hidrologi Hilir dalam kondisi kritis, akibatnya, sebagian besar DAS Bengawan Solo hilir terletak di Kabupaten Gresik Utara dan Lamongan, setiap tahunnya dibanjiri oleh luapan air dari hulu. Sebaliknya hulu Lamongan selalu kekurangan air di musim kemarau. Studi ini akan memanfaatkan Bendung Gerak Sembayat sebagai reservoir penampung yang bisa menyimpan air selama musim kemarau dan bisa menguras air di musim hujan. Inflow waduk BGS diperoleh dengan metode pembangkitan data menggunakan Thomas Fiering. Data rata-rata debit harian setiap bulan selama 24 tahun dinaikkan menjadi data arus statistik yang bisa digunakan selama 50 tahun ke depan. Perhitungan kebutuhan air baku berdasarkan kriteria perencanaan air bersih Direktorat Jenderal Cipta Karya, Kementerian Pekerjaan Umum tahun 2000, sedangkan kebutuhan air irigasi dihitung berdasarkan Standar Perencanaan Irigasi (KP-01) pada tahun 1986. Ada 6 simulasi Untuk mendapatkan hasil yang paling optimal. Sebelas alternatif ini diproses dengan metode Water Balance untuk menganalisis kebutuhan air untuk perikanan, irigasi, domestik dan industri. Hasil simulasi alternatif diperoleh grafik kuadran optimal paling optimal yaitu pada neraca air Tanaman Biji-bijian yang ada dengan total kebutuhan air 61411.61 (106 m3

3D Finite Element Study on: Bar Splinted Implants Supporting Partial Denture in the Reconstructed Mandible

AIM: This study aimed to estimate the stress patterns induced by the masticatory loads on a removable prosthesis supported and retained by bar splinted implants placed in the reconstructed mandible with two different clip materials and without clip, in the fibula-jaw bone and prosthesis using finite element analysis.METHODS: Two 3D finite element models were constructed, that models components were modeled on commercial CAD/CAM software then assembled into finite element package. Vertical loads were applied simulating the masticatory forces unilaterally in the resected site and bilaterally in the central fossa of the lower first molar as 100N (tension and compression). Analysis was based on the assumption full osseointegration between different types of bones, and between implants and fibula while fixing the top surface of the TMJ in place.RESULTS: The metallic bar connecting the three implants is insensitive to the clips material. Its supporting implants showed typical behavior with maximum stress values at the neck region. Fibula and jaw bone showed stresses within physiologic, while clips material effect seems to be very small due to its relatively small size.CONCLUSION: Switching loading force direction from tensile to compression did-not change the stresses and deformations distribution, but reversed their sign from positive to negative

Oncogenic challenge of bromocriptine and L-arginine versus conventional antidiabetics on diethyl nitrosamine-induced liver tumorigenesis in diabetic rats: focus on AMPK activation

Background: Diabetes mellitus (DM) is associated with a spectrum of cancers where the metabolic antecedents, consequences, and therapy might affect cancer risk. The association between hepatocellular carcinoma (HCC) and DM had been confirmed. Approaches to HCC prevention focus on the molecular regulators of the disease process defined as the inflammation-fibrosis-cancer axis. The AMP-activated protein kinase (AMPK) is an interesting metabolic tumor suppressor and a promising target for cancer prevention and therapy. This study aimed to investigate the effects of bromocriptine mesylate and L-arginine on hepatic carcinogenesis on a rat model of hepatic neoplasia induced by diethyl nitrosamine (DENA) and promoted by type-2 DM in contrast to the conventional antidiabetics.Methods: One hundred male Wistar rats were randomly assigned into two sets; control set (normal, HCC, DM, and combined HCC/DM) and treated set where rats received one of the following drugs for another 5 weeks: insulin glargine, glimepiride, metformin, pioglitazone, bromocriptine mesylate, or L-arginine. Bodyweight changes, blood glucose level, liver functions tests, serum C-peptide and alpha-fetoprotein (AFP), and hepatic activated AMPK were assessed beside the hepatic histopathological changes.Results: Equivalent to metformin, bromocriptine and L-arginine treatment significantly reduced AFP, despite their minor glycemic control. L-arginine induced AMPK activation, yet less than metformin. Histopathologic examination revealed a reduction in hepatic intra-lobular chronic inflammatory cell infiltration, steatosis and necrosis by metformin, bromocriptine, and L-arginine. Hepatic necro-inflammatory changes were most prominent in insulin-treated rats.Conclusions: L-arginine and bromocriptine mesylate prevent early neoplastic changes almost equivalent to metformin at least partially via hepatic AMPK activation

Differentiation of a contractile, ureter-like tissue, from Embryonic Stem cell-derived ureteric bud and <i>Ex-Fetu</i> mesenchyme

BACKGROUND: There is intense interest in replacing kidneys from stem cells. It is now possible to produce, from embryonic or induced pluripotent stem cells, kidney organoids that represent immature kidneys and display some physiologic functions. However, current techniques have not yet resulted in renal tissue with a ureter, which would be needed for engineered kidneys to be clinically useful. METHODS: We used a published sequence of growth factors and drugs to induce mouse embryonic stem cells to differentiate into ureteric bud tissue. We characterized isolated engineered ureteric buds differentiated from embryonic stem cells in three-dimensional culture and grafted them into ex fetu mouse kidney rudiments. RESULTS: Engineered ureteric buds branched in three-dimensional culture and expressed Hoxb7, a transcription factor that is part of a developmental regulatory system and a ureteric bud marker. When grafted into the cortex of ex fetu kidney rudiments, engineered ureteric buds branched and induced nephron formation; when grafted into peri-Wolffian mesenchyme, still attached to a kidney rudiment or in isolation, they did not branch but instead differentiated into multilayer ureter-like epithelia displaying robust expression of the urothelial marker uroplakin. This engineered ureteric bud tissue also organized the mesenchyme into smooth muscle that spontaneously contracted, with a period a little slower than that of natural ureteric peristalsis. CONCLUSIONS: Mouse embryonic stem cells can be differentiated into ureteric bud cells. Grafting those UB-like structures into peri-Wolffian mesenchyme of cultured kidney rudiments can induce production of urothelium and organize the mesenchyme to produce rhythmically contracting smooth muscle layers. This development may represent a significant step toward the goal of renal regeneration

25-Hydroxy Vitamin D, Adiponectin Levels and Cardiometabolic Risk Factors in a Sample of Obese Children

BACKGROUND: Association between vitamin D, adiponectin and obesity is a matter of debate, as they play important role in linking obesity with different cardio metabolic risk factors.AIM: Evaluation of association between metabolic risk factors with both adiponectin and 25-Hydroxy vitamin D [25(OH) D] levels and that between adiponectin and [25(OH) D] among obese Egyptian children.SUBJECTS AND METHODS: This case-control cross sectional study consisted of 65 obese and 30 healthy children, aged 8-11 years. 25(OH) D, serum adiponectin, total cholesterol, triglycerides, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol were measured.RESULTS: The mean 25(OH)D and adiponectin levels in the obese were lower than that in control group (ð‘ƒ&lt;0.000). 25(OH)D were inversely correlated with body mass index, triglyceride, total cholesterol and LDL-cholesterol. While adiponectin level were inversely correlated with systolic and diastolic blood pressure, and positively correlated with high-density lipoprotein-cholesterol. However, there is no relation between 25(OH) D and adiponectin levels among obese children and total sample.CONCLUSION: Inspite of strong association between vitamin D and adiponectin levels with metabolic risk factors and obesity, there is no relation between 25(OH)D and adiponectin levels. In obese children, There are significant negative correlations between 25(OH)D with lipid profile, and between adiponectin levels with blood pressure

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Medical prospects of cryptosporidiosis in vivo control using biofabricated nanoparticles loaded with Cinnamomum camphora extracts by Ulva fasciata

Background and Aim: Global efforts are continuing to develop preparations against cryptosporidiosis. This study aimed to investigate the efficacy of biosynthesized Ulva fasciata loading Cinnamomum camphora oil extract on new zinc oxide nanoparticles (ZnONPs shorten to ZnNPs) and silver nanoparticles (AgNPs) as alternative treatments for Cryptosporidium parvum experimental infection in rats. Materials and Methods: Oil extract was characterized by gas chromatography-mass spectrometry, loaded by U. fasciata on ionic-based ZnO and NPs, and then characterized by transmission electron microscopy, scanning electron microscopy, and X-ray diffraction. Biosafety and toxicity were investigated by skin tests. A total of 105 C. parvum oocysts/rat were used (n = 81, 2–3 W, 80–120 g, 9 male rats/group). Oocysts shedding was counted for 21 d. Doses of each preparation in addition to reference drug were administered daily for 7 d, starting on post-infection (PI) day (3). Nitazoxanide (100 mg) was used as the reference drug. After 3 weeks, the rats were sacrificed for postmortem examination and histopathological examination. Two blood samples/rat/group were collected on the 21st day. Ethylenediaminetetraacetic acid blood samples were also used for analysis of biochemistry, hematology, immunology, micronucleus prevalence, and chromosomal abnormalities. Results: C. camphora leaves yielded 28.5 ± 0.3 g/kg oil and 20 phycocompounds were identified. Spherical and rod-shaped particles were detected at 10.47–30.98 nm and 18.83–38.39 nm, respectively. ZnNPs showed the earliest anti-cryptosporidiosis effect during 7–17 d PI. Other hematological, biochemical, immunological, histological, and genotoxicity parameters were significantly fruitful; hence, normalized pathological changes induced by infestation were observed in the NPs treatments groups against the infestation-free and Nitazoxanide treated group. Conclusion: C. camphora, U. fasciata, ZnNPs, and AgNPs have refluxed the pathological effects of infection as well as positively improved host physiological condition by its anticryptosporidial immunostimulant regenerative effects with sufficient ecofriendly properties to be proposed as an alternative to traditional drugs, especially in individuals with medical reactions against chemical commercial drugs