Adenosine kinase inhibition selectively promotes rodent and porcine islet β-cell replication

Diabetes is a pathological condition characterized by relative insulin deficiency, persistent hyperglycemia, and, consequently, diffuse micro- and macrovascular disease. One therapeutic strategy is to amplify insulin-secretion capacity by increasing the number of the insulin-producing β cells without triggering a generalized proliferative response. Here, we present the development of a small-molecule screening platform for the identification of molecules that increase β-cell replication. Using this platform, we identify a class of compounds [adenosine kinase inhibitors (ADK-Is)] that promote replication of primary β cells in three species (mouse, rat, and pig). Furthermore, the replication effect of ADK-Is is cell type-selective: treatment of islet cell cultures with ADK-Is increases replication of β cells but not that of α cells, PP cells, or fibroblasts. Short-term in vivo treatment with an ADK-I also increases β-cell replication but not exocrine cell or hepatocyte replication. Therefore, we propose ADK inhibition as a strategy for the treatment of diabetes.Stem Cell and Regenerative Biolog

Web-based patient-reported outcome measures for personalized treatment and care (PROMPT-Care) : multicenter pragmatic nonrandomized trial

Background: Despite the acceptability and efficacy of e–patient-reported outcome (ePRO) systems, implementation in routine clinical care remains challenging. Objective: This pragmatic trial implemented the PROMPT-Care (Patient Reported Outcome Measures for Personalized Treatment and Care) web-based system into existing clinical workflows and evaluated its effectiveness among a diverse population of patients with cancer. Methods: Adult patients with solid tumors receiving active treatment or follow-up care in four cancer centers were enrolled. The PROMPT-Care intervention supported patient management through (1) monthly off-site electronic PRO physical symptom and psychosocial well-being assessments, (2) automated electronic clinical alerts notifying the care team of unresolved clinical issues following two consecutive assessments, and (3) tailored online patient self-management resources. Propensity score matching was used to match controls with intervention patients in a 4:1 ratio for patient age, sex, and treatment status. The primary outcome was a reduction in emergency department presentations. Secondary outcomes were time spent on chemotherapy and the number of allied health service referrals. Results: From April 2016 to October 2018, 328 patients from four public hospitals received the intervention. Matched controls (n=1312) comprised the general population of patients with cancer, seen at the participating hospitals during the study period. Emergency department visits were significantly reduced by 33% (P=.02) among patients receiving the intervention compared with patients in the matched controls. No significant associations were found in allied health referrals or time to end of chemotherapy. At baseline, the most common patient reported outcomes (above-threshold) were fatigue (39%), tiredness (38.4%), worry (32.9%), general wellbeing (32.9%), and sleep (24.1%), aligning with the most frequently accessed self-management domain pages of physical well-being (36%) and emotional well-being (23%). The majority of clinical feedback reports were reviewed by nursing staff (729/893, 82%), largely in response to the automated clinical alerts (n=877). Conclusions: Algorithm-supported web-based systems utilizing patient reported outcomes in clinical practice reduced emergency department presentations among a diverse population of patients with cancer. This study also highlighted the importance of (1) automated triggers for reviewing above-threshold results in patient reports, rather than passive manual review of patient records; (2) the instrumental role nurses play in managing alerts; and (3) providing patients with resources to support guided self-management, where appropriate. Together, these factors will inform the integration of web-based PRO systems into future models of routine cancer care

Genome-wide gene expression profiling identifies overlap with malignant adrenocortical tumours and novel mechanisms of inefficient steroidogenesis in familial ACTH-independent macronodular adrenal hyperplasia.

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of sporadic or familial late-onset Cushing's syndrome. It is a cytologically benign disease, of unknown pathogenesis, and characterised by inefficient steroidogenesis, ascribed to differential cellular localisation of steroidogenic enzymes. The objectives were to determine the molecular mechanisms involved in the pathogenesis of familial AIMAH tumours and the mechanisms of their inefficient steroidogenesis. Using Affymetrix Human GeneChip® HumanGene 1.0 ST arrays, we compared the genome-wide gene expression profile of two AIMAH nodules from each of three affected siblings with normal adrenal cortex and analysed the data for differential expression and using Ingenuity Pathway Analysis, Gene Set Enrichment Analysis and Motif Activity Response Analysis. Expression profiling identified: (i) that amongst the most highly differentially expressed genes were ones known to have involvement in tumorigenesis and metastasis; (ii) enrichment for differentially expressed genes in sporadic AIMAH and other benign and malignant adrenocortical tumours and (iii) reduced activity of key transcriptional regulators (Steroidogenic factor-1, SF-1 and transcription factor Sp1, Sp1) of steroidogenic enzymes. Genome-wide gene expression studies of familial AIMAH nodules have identified overlap with malignant adrenocortical tumours, which is intriguing given the benign biological behaviour of these tumours. This requires further study. Novel mechanisms of inefficient steroidogenesis were also identified

Polyamine functionalised ion exchange resins: Synthesis, characterisation and uranyl uptake

A series of linear polyamine functionalised weak base anion exchange resins have been synthesised using the Merrifield resin and characterised using infra-red spectroscopy, thermogravimetry, elemental analysis and solid state 13 C nuclear magnetic resonance spectroscopy. Uptake behaviour towards uranium (as uranyl) from sulfuric acid media has been assessed as a function of pH and sulfate concentration, with comparison to a commercially available weak base anion exchange resin, Purolite S985. Synthetic polyamine resins were seen to outperform the commercial resin at industrially relevant uranyl concentrations, with a trend of increased uptake being seen with increasing polyamine chain length. Uranium loading isotherm studies have been performed and fit with the Langmuir and Dubinin-Radushkevich isotherm models, with a maximum loading capacity observed being 269.50 mg g −1 for the longest polyamine chain studied. Extended X-ray absorption fine structure experiments have been used to determine uranium coordination environment on the resin surface, showing a [UO 2 (SO 4 ) 3 ] 4− species. This coordination knowledge was employed to develop an extraction mechanism and derive an isotherm model based on the law of mass action

Association Between Advanced Maternal Age and Maternal and Neonatal Morbidity: A Cross-Sectional Study on a Spanish Population

Background and objective: Over recent decades, a progressive increase in the maternal age at childbirth has been observed in developed countries, posing a health risk for both women and infants. The aim of this study was to analyze the association between advanced maternal age (AMA) and maternal and neonatal morbidity. Material and methods: A cross-sectional study of 3,315 births was conducted in the north of Spain in 2014. We compared childbirth between women aged 35 years or older, with a reference group of women aged between 24 and 27 years. AMA was categorized based on ordinal ranking into 35-38 years, 39-42 years, and >42 years to estimate a dose-response pattern (the older the age, the greater the risk). As an association measure, crude and adjusted Odds Ratios (OR) were estimated by non-conditional logistic regression and 95% Confidence Intervals (95%CI) were calculated. Results: Repeated abortions were more common among women of AMA in comparison to pregnant women aged 24-27 years (reference group): adjusted OR = 2.68; 95%CI (1.52-4.73). A higher prevalence of gestational diabetes was also observed among women of AMA, reaching statistical significance when restricted to first time mothers: adjusted OR = 8.55; 95%CI (1.12-65.43). In addition, the possibility of an instrumental delivery was multiplied by 1.6 and the possibility of a cesarean by 1.5 among women of AMA, with these results reaching statistical significance, and observing a dose-response pattern. Lastly, there were associations between preeclampsia, preterm birth (<37 weeks) and low birthweight, however without reaching statistical significance. Conclusion: Our results support the association between AMA and suffering repeated abortions. Likewise, being of AMA was associated with a greater risk of suffering from gestational diabetes, especially among primiparous women, as well as being associated with both instrumental deliveries and cesareans among both primiparous and multiparous women

Chromogenic and fluorogenic chemosensors and reagents for anions. A comprehensive review of the year 2009

This critical review is focused on examples reported in the year 2009 dealing with the design of chromogenic and fluorogenic chemosensors or reagents for anions (264 references). © 2011 The Royal Society of Chemistry.Moragues Pons, ME.; Martínez Mañez, R.; Sancenón Galarza, F. (2011). Chromogenic and fluorogenic chemosensors and reagents for anions. A comprehensive review of the year 2009. Chemical Society Reviews. 40(5):2593-2643. doi:10.1039/c0cs00015aS25932643405Schmidtchen, F. P., Gleich, A., & Schummer, A. (1989). Selective molecular hosts for anions. Pure and Applied Chemistry, 61(9), 1535-1546. doi:10.1351/pac198961091535Dietrich, B. (1993). Design of anion receptors: Applications. Pure and Applied Chemistry, 65(7), 1457-1464. doi:10.1351/pac199365071457Atwood, J. L., Holman, K. T., & Steed, J. W. (1996). Laying traps for elusive prey: recent advances in the non-covalent binding of anions. Chemical Communications, (12), 1401. doi:10.1039/cc9960001401Schmidtchen, F. 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Chloride ion recognition using thiourea/urea based receptors incorporated into 1,3-disubstituted calix[4]arenes. New Journal of Chemistry, 33(3), 675. doi:10.1039/b816610bBoiocchi, M., Fabbrizzi, L., Garolfi, M., Licchelli, M., Mosca, L., & Zanini, C. (2009). Templated Synthesis of Copper(II) Azacyclam Complexes Using Urea as a Locking Fragment and Their Metal-Enhanced Binding Tendencies towards Anions. Chemistry - A European Journal, 15(42), 11288-11297. doi:10.1002/chem.200901364Lin, Y.-S., Tu, G.-M., Lin, C.-Y., Chang, Y.-T., & Yen, Y.-P. (2009). Colorimetric anion chemosensors based on anthraquinone: naked-eye detection of isomeric dicarboxylate and tricarboxylate anions. New Journal of Chemistry, 33(4), 860. doi:10.1039/b811172cQing, G.-Y., Sun, T.-L., Wang, F., He, Y.-B., & Yang, X. (2009). Chromogenic Chemosensors forN-Acetylaspartate Based on Chiral Ferrocene-Bearing Thiourea Derivatives. European Journal of Organic Chemistry, 2009(6), 841-849. doi:10.1002/ejoc.200800961Lu, Q.-S., Dong, L., Zhang, J., Li, J., Jiang, L., Huang, Y., … Yu, X.-Q. (2009). Imidazolium-Functionalized BINOL as a Multifunctional Receptor for Chromogenic and Chiral Anion Recognition. Organic Letters, 11(3), 669-672. doi:10.1021/ol8027303Bao, X., Yu, J., & Zhou, Y. (2009). Selective colorimetric sensing for F− by a cleft-shaped anion receptor containing amide and hydroxyl as recognition units. Sensors and Actuators B: Chemical, 140(2), 467-472. doi:10.1016/j.snb.2009.04.056Bhardwaj, V. K., Hundal, M. S., & Hundal, G. (2009). A tripodal receptor bearing catechol groups for the chromogenic sensing of F− ions via frozen proton transfer. Tetrahedron, 65(41), 8556-8562. doi:10.1016/j.tet.2009.08.023Caltagirone, C., Mulas, A., Isaia, F., Lippolis, V., Gale, P. A., & Light, M. E. (2009). Metal-induced pre-organisation for anion recognition in a neutral platinum-containing receptor. Chemical Communications, (41), 6279. doi:10.1039/b912942aShiraishi, Y., Maehara, H., Sugii, T., Wang, D., & Hirai, T. (2009). A BODIPY–indole conjugate as a colorimetric and fluorometric probe for selective fluoride anion detection. Tetrahedron Letters, 50(29), 4293-4296. doi:10.1016/j.tetlet.2009.05.018Shiraishi, Y., Maehara, H., & Hirai, T. (2009). Indole-azadiene conjugate as a colorimetric and fluorometric probe for selective fluoride ion sensing. Organic & Biomolecular Chemistry, 7(10), 2072. doi:10.1039/b821466bBhosale, S. V., Bhosale, S. V., Kalyankar, M. B., & Langford, S. J. (2009). A Core-Substituted Naphthalene Diimide Fluoride Sensor. Organic Letters, 11(23), 5418-5421. doi:10.1021/ol9022722Lin, Z., Chen, H. C., Sun, S.-S., Hsu, C.-P., & Chow, T. J. (2009). Bifunctional maleimide dyes as selective anion sensors. Tetrahedron, 65(27), 5216-5221. doi:10.1016/j.tet.2009.04.090Yoo, J., Kim, M.-S., Hong, S.-J., Sessler, J. L., & Lee, C.-H. (2009). Selective Sensing of Anions with Calix[4]pyrroles Strapped with Chromogenic Dipyrrolylquinoxalines. The Journal of Organic Chemistry, 74(3), 1065-1069. doi:10.1021/jo802059cShang, X.-F., Li, J., Lin, H., Jiang, P., Cai, Z.-S., & Lin, H.-K. (2009). Anion recognition and sensing of ruthenium(ii) and cobalt(ii) sulfonamido complexes. Dalton Transactions, (12), 2096. doi:10.1039/b804445gDydio, P., Zieliński, T., & Jurczak, J. (2009). Bishydrazide Derivatives of Isoindoline as Simple Anion Receptors. The Journal of Organic Chemistry, 74(4), 1525-1530. doi:10.1021/jo802288uZimmermann-Dimer, L. M., Reis, D. C., Machado, C., & Machado, V. G. (2009). Chromogenic anionic chemosensors based on protonated merocyanine solvatochromic dyes in trichloromethane and in trichloromethane–water biphasic system. Tetrahedron, 65(21), 4239-4248. doi:10.1016/j.tet.2009.03.049Goswami, S., Hazra, A., Chakrabarty, R., & Fun, H.-K. (2009). 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Mechanomyographic amplitude and frequency responses during dynamic muscle actions: a comprehensive review

The purpose of this review is to examine the literature that has investigated mechanomyographic (MMG) amplitude and frequency responses during dynamic muscle actions. To date, the majority of MMG research has focused on isometric muscle actions. Recent studies, however, have examined the MMG time and/or frequency domain responses during various types of dynamic activities, including dynamic constant external resistance (DCER) and isokinetic muscle actions, as well as cycle ergometry. Despite the potential influences of factors such as changes in muscle length and the thickness of the tissue between the muscle and the MMG sensor, there is convincing evidence that during dynamic muscle actions, the MMG signal provides valid information regarding muscle function. This argument is supported by consistencies in the MMG literature, such as the close relationship between MMG amplitude and power output and a linear increase in MMG amplitude with concentric torque production. There are still many issues, however, that have yet to be resolved, and the literature base for MMG during both dynamic and isometric muscle actions is far from complete. Thus, it is important to investigate the unique applications of MMG amplitude and frequency responses with different experimental designs/methodologies to continually reassess the uses/limitations of MMG