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ObjectivesTo assess the association of clinical factors and investigation results (blood and urine) with imaging abnormalities (ultrasound of the kidneys, ureters and bladder; dimercaptosuccinic acid scan; and/or micturating cystourethrogram) and recurrent urinary tract infections (UTIs) in infants ≤3 months old presenting with their first febrile UTI.MethodsWe conducted a retrospective cohort study of infants ≤3 months old with first febrile UTI admitted from 2010 to 2016. Multivariable logistic regression model was used to analyse the association of imaging abnormalities and recurrent UTI with covariates selected a priori: age at presentation, maximum temperature, duration of illness at presentation, interval between start of antibiotics and fever resolution, C-reactive protein, total white cell count on the full blood count, bacteraemia, white cell count on the urinalysis and non-Escherichia coligrowth in the urine culture (non-E. coliUTI).ResultsThere were 190 infants but 12 did not undergo any imaging. Median age at presentation was 63 days (IQR 41–78). Twenty-four patients had imaging abnormalities. Non-E. coliUTI (adjusted OR (aOR) 5.01, 95% CI 1.65 to 15.24, p=0.004) was independently associated with imaging abnormalities, while bacteraemia (aOR 4.93, 95% CI 1.25 to 19.43, p=0.022) and non-E. coliUTI (aOR 5.06, 95% CI 1.90 to 13.48, p=0.001) were independently associated with recurrent UTI.ConclusionNon-E. coliUTI at the first febrile UTI in infants ≤3 months old may be useful in predicting imaging abnormalities while bacteraemia and non-E. coliUTI may be useful to predict recurrent UTI.

Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi-gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one-third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1-14.8; p 0.001), and proteinuria in the absence of nephrotic syndrome (OR 4.6; 95% CI 1.8-11.8; p = 0.001) at first manifestation. Among patients who first presented with proteinuria without nephrotic syndrome, the genetic diagnostic rates were60% when a second risk factor (positive family history or extrarenal manifestation) co-existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent.

A completely water-soluble, high quantum yield blue-fluorescent benzimidazole derivative (AQ), containing a rigid benzimidazole-thiophene structure, was synthesized. Among 21 metal ions, the fluorescence of AQ was selectively turned off by Cu2+ to form an AQ-Cu2+ ensemble. Thereafter, the fluorescence of the AQ-Cu2+ ensemble was turned on by sulfide (S2-) with high selectivity and sensitivity in pure water solution. In comparison with AQ-Ag+ and AQ-Hg2+ ensembles, AQ-Cu2+ was the only ensemble that was capable of detecting a sulfide anion. Also, the fluorescence intensity of AQ was linearly proportional to the concentration of Cu2+ and S2-. Both Cu2+ and S2- were detected within a minute in vitro. Moreover, AQ worked best in the pH range of 5-10 and had a limit of detection of 50 nM and 354 nM for Cu2+ and S2- respectively. It was employed for the detection of sulfide in human lung cancer A549 cells with low cytotoxicity.

In this study, the synthesis of [2]rotaxanes as fluorescent metal ion sensors has been demonstrated. [2]Rotaxanes, RA-H·PF6, RRA and RRB, undergo photoelectron transfer resulting in fluorescence quenching. Before the diimine (dynamic covalent bond) reduction on the macrocyclic ring, the dynamic [2]rotaxane RA-H·PF6 can be hydrolyzed and turned fluorescent by trivalent metal ions, giving fluorescence at λmax 424 nm. After reduction of the imines, the reduced [2]rotaxanes RRA and RRB are kinetically stable and highly selective to Au3+ binding among 27 metal ions in a water-compatible (50 vol%) solution with working fluorescence in the range of pH 4–10. 50-Fold and 1.2-fold fluorescence turn-on after addition of Au3+ has been observed for RRA and RRB, respectively. Metal interference on Au3+ detection is insignificant, and thereby the fluorescence intensity is linearly proportional to the concentration of Au3+ until excess. The solid-state crystal structure of RRA shows the mechanically interlocked structure (mechanical bond). The bioimaging experiment of RRB with HeLa cells demonstrates the potential application of these mechanically interlocked molecules for metal ion detection in aqueous media and biological systems.

Is the oncogene MYC upregulated or hyperactive? In the majority of human cancers, finding agents that target c-MYC has proved difficult. Here we report specific bacterial effector molecules that inhibit cellular MYC (c-MYC) in human cells. We show that uropathogenic Escherichia coli (UPEC) degrade the c-MYC protein and attenuate MYC expression in both human cells and animal tissues. c-MYC protein was rapidly degraded by both cell-free bacterial lysates and the purified bacterial protease Lon. In mice, intravesical or peroral delivery of Lon protease delayed tumor progression and increased survival in MYC-dependent bladder and colon cancer models, respectively. These results suggest that bacteria have evolved strategies to control c-MYC tissue levels in the host and that the Lon protease shows promise for therapeutic targeting of c-MYC in cancer.

In this study, we report a new class of rhodamine-based fluorescent sensors for highly selective and sensitive detection of Pd

Tenofovir is a nucleoside reverse transcriptase inhibitor commonly used to treat human immunodeficiency virus (HIV) infection in children and adolescents. We report a case of an HIV-positive adolescent male who had been treated with an antiretroviral regimen consisting of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) and lopinavir/ritonavir (LPV/r) with a stable CD4 count. Two and a half years after starting tenofovir, he experienced a right third metatarsal shaft fracture after minor trauma, which was treated successfully with a cast. He was found to have osteopenia for which he was treated with oral phosphate and calcium/vitamin D supplementation. Three months later, he then presented with severe hypokalemia, hypophosphatemia, normal anion gap metabolic acidosis, glycosuria, and proteinuria, which were consistent with a diagnosis of acquired Fanconi's syndrome. Subsequently, his electrolyte abnormalities were corrected with replacement of potassium, phosphate, and bicarbonate (Shohl's solution). His antiretroviral regimen was switched to abacavir/lamivudine and raltegravir. Acquired Fanconi's syndrome is a known but uncommon adverse effect of treatment with tenofovir, and an awareness that it can cause osteopenia and present with fractures can alert the physician to manage and prevent this potentially serious side effect.

In this study, we report a new class of rhodamine-based fluorescent sensors for highly selective and sensitive detection of Pd2+ ions in aqueous medium. A rhodamine-based palladium sensor RPS and a coumarin-rhodamine Forster resonance energy transfer (FRET)-pair based palladium sensor FPS were synthesized with the designed podand ligand for Pd2+ ion recognition. They showed both colorimetric change and fluorometric change in the presence of Pd2+ ion due to the opening of their spirolactam rings. Both chemosensors are highly selective to Pd2+ over the other 24 different metal ions and they are selective to palladium species in +2 oxidation state, RPS showed a 70-fold fluorescent turn-on while FPS showed a 1.75-fold ratiometric change at I599/I470. Furthermore, RPS showed low cell cytotoxicity and it was successfully used to image Pd2+ in BEAS-2B lung epithelial cells. © 2019 Elsevier Science. All rights reserved.