BACKGROUND Small bowel bacterial overgrowth (SBBO) is a challenge in the management of pediatric intestinal failure (PIF). Our goal was to determine the proportion of patients treated for SBBO and factors related to its development. METHODS We completed a retrospective analysis of PIF patients referred between 2008 and 2014. Data were collected on factors related to intestinal failure (IF) and SBBO. The cohort was stratified on the diagnosis of SBBO and refractory SBBO. Statistical testing completed using t-test, χ2 test, and logistic regression. RESULTS Thirty-five of 102 patients developed SBBO (34%), and 16 (16%) had refractory SBBO. SBBO was more likely in gastroschisis (40.0% vs 19.4%, P = .025), a shorter residual small bowel (SB) (45.4% vs 66.5%, P = .004), and patients were less likely to wean from parenteral nutrition (PN) (51.4% vs 85.1%, P less then .0001). Refractory SBBO patients were likely to have gastroschisis (50.0% vs 22.1%, P = .020) and a shorter residual SB and large bowel remaining (23.2% vs 65.9%, P less then .0001 and 60.6% vs 79.4%, P = .03, respectively) and less likely to wean from PN (37.5% vs 80.2%, P = .001). Logistic regression demonstrated that longer SB residual was protective (P = .001; odds ratio [OR], 0.95; 95% CI, 0.93-0.99), and short bowel syndrome (SBS) as a cause of IF was a risk factor (P = .001; OR, 0.04; 95% CI, 0.01-0.27). CONCLUSION A longer SB remnant was protective against SBBO. Patients with SBBO were more likely to have PIF caused by SBS. © 2020 American Society for Parenteral and Enteral Nutrition.The chromium(III) complex [CrIII(ddpd)2]3+ (molecular ruby) is reduced to the genuine chromium(II) complex [CrII(ddpd)2]2+ with d4 electron configuration. This reduced molecular ruby represents one of the very few chromium(II) complexes showing spin crossover (SCO). The reversible SCO is gradual with Tc around room temperature. The low-spin and high-spin chromium(II) isomers exhibit distinct spectroscopic and structural properties (UV/Vis/NIR, IR, EPR spectroscopies, single-crystal XRD). Excitation of [CrII(ddpd)2]2+ with UV light at 20 and 290 K generates electronically excited states with microsecond lifetimes. This initial study on the unique reduced molecular ruby paves the way for thermally and photochemically switchable magnetic systems based on chromium complexes complementing the well-established iron(II) SCO systems. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.We sought to evaluate the trends and outcomes of patients with left ventricular assist devices (LVADs) and inotropes at the time of listing for heart transplantation. Adults with an LVAD implanted and listed with 1A status were identified in the United Network for Organ Sharing (UNOS) registry between 2010 and 2017. Patients were grouped according to the presence or absence of inotropes at the time of listing and transplantation. A total of 2,714 patients were included in the study including 664 patients on inotropes at the time of listing, 235 at the time of transplantation and 118 on inotropes both at listing and at the time of transplantation. Patients on LVAD and inotropes at the time of listing were more frequently supported with a right ventricular assist device (RVAD) (p less then 0.001), had higher risk of death in the waiting list (sub-hazard ratio [SHR] =1.48, 95% CI 1.14-1.90, p=0.002) and were less likely to be transplanted (SHR= 0.70, 95% CI 0.63-0.78, p less then 0.001) compared with those not on inotropes, after adjusting for described confounders. Approximately 1 in 10 LVAD recipients listed as status 1A are on inotropic therapy at the time of heart transplantation. Patients on LVAD and inotropes have worse outcomes in terms of survival and lower rates of transplantation. This article is protected by copyright. All rights reserved.BACKGROUND Concomitant therapy is a recommended first-line treatment for H. pylori infection in most national or international consensuses. Reverse hybrid therapy is a modified 14-day concomitant therapy without clarithromycin and metronidazole in the final 7 days. AIM To test whether 14-day reverse hybrid therapy is non-inferior to 14-day concomitant therapy in the first-line treatment of H. pylori infection. METHODS H. pylori-infected adult patients were randomly assigned to receive either reverse hybrid therapy (dexlansoprazole 60 mg o.d. plus amoxicillin 1 g, b.d. for 14 days, and clarithromycin 500 mg plus metronidazole 500 mg b.d. for initial 7 days) or concomitant therapy (dexlansoprazole 60 mg once o.d. plus amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg b.d. for 14 days). H. pylori status was assessed 6 weeks after the end of treatment. RESULTS H. pylori-infected participants (n = 248) were randomized to receive either 14-day reverse hybrid therapy (n = 124) or 14-day concomitant therapy (n = 124). Intention-to-treat analysis demonstrated that the two therapies had comparable eradication rate (95.2% vs 93.5%; 95% confidence interval, -4.0% ~ 7.4%; P = 0.582). However, reverse hybrid therapy had a much lower frequency of adverse events than concomitant therapy (20.2 % vs. 38.7%, P = 0.001). The two therapies exhibited comparable drug adherence (93.5% vs 87.9%, P = 0.125). CONCLUSIONS 14-day reverse hybrid therapy and 14-day concomitant therapy are equivalent in efficacy for the first-line treatment of H pylori infection. However, reverse hybrid therapy has fewer adverse events compared to concomitant therapy. This article is protected by copyright. All rights reserved.Enzymes, receptors and carrier proteins discriminate between enantiomers of natural and synthetic chemicals. While the structural details of this phenomenon have been investigated in enzymes and receptors, much less is known for carrier proteins of hydrophobic ligands, particularly concerning the contribution of asymmetric centres in the side chains of amino acids to chirally selective binding. Working with a pig odorant-binding protein, we have found that the replacement of either one or both isoleucine residues in the binding pocket by leucines abolishes discrimination of menthol and carvone enantiomers. The results indicate that isoleucines are crucial for chiral discrimination of hydrophobic ligands, and that asymmetry in the side chain may be as important as the overall asymmetry of the protein. The results provide suggestions and guidelines for improving chiral selectivity of binding proteins and enzymes, with consequent applications in the production of enantiomerically pure drugs. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Protein folding quality control in cells requires the activity of a class of proteins known as molecular chaperones. Heat shock protein-90 (Hsp90), a multidomain ATP driven molecular machine, is a prime representative of this family of proteins. Interactions between Hsp90, its co-chaperones, and client proteins have been shown to be important in facilitating the correct folding and activation of clients. Hsp90 levels and functions are elevated in tumor cells. Here, we computationally predict the regions on the native structures of clients c-Abl, c-Src, Cdk4, B-Raf and Glucocorticoid Receptor, that have the highest probability of undergoing local unfolding, despite being ordered in their native structures. Such regions represent potential ideal interaction points with the Hsp90-system. We synthesize mimics spanning these regions and confirm their interaction with partners of the Hsp90 complex (Hsp90, Cdc37 and Aha1) by Nuclear Magnetic Resonance (NMR). Designed mimics selectively disrupt the association of their respective clients with the Hsp90 machinery, leaving unrelated clients unperturbed and causing apoptosis in cancer cells. Overall, selective targeting of Hsp90 protein-protein interactions is achieved without causing indiscriminate degradation of all clients, setting the stage for the development of therapeutics based on specific chaperoneclient perturbation. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Diabetic neuropathic hyperalgesia is one of the most common diabetes complications. The physiopathological mechanism of hyperalgesia and the reason by which this condition affects only part of the diabetic patients still unclear. We tested whether an adaptation of primary afferent neurons to hyperglycemia could prevent the development of hyperalgesia. Hyperglycemia was induced in male Wistar rats by a daily administration of a low-dose of streptozotocin (STZ), during five consecutive days. Glycemia and mechanical nociceptive thresholds were measured at days 0, 3, 7, and 14 after starting the streptozotocin treatment. In parallel, dorsal root ganglia (DRG) neurons were collected from healthy male Wistar rats and cultured in different glucose concentrations (mimicking slow or fast increase of hyperglycemia), and used for calcium imaging and Western-blot analyses. Rats with a slow increase of glycemia did not develop hyperalgesia, while rats with a fast increase of glycemia developed hyperalgesia. DRG neurons suddenly incubated in DMEM containing a high glucose concentration, showed a significant increase of calcium influx. However, DRG neurons incubated in DMEM and receiving increasing doses of glucose, had the same calcium influx observed in control neurons. The activation of AMPK (α1/α2) was greater in L5-L6 DRG of hyperglycemic and non-hyperalgesic rats, when compared with hyperglycemic and hyperalgesic rats. Our data suggest that the onset speed of hyperglycemia could be related to the development of diabetic neuropathic hyperalgesia, as a maladaptive consequence associated with low activation of AMPK (α1/α2) in peripheral nociceptive neurons when the glycemia suddenly increases. This article is protected by copyright. All rights reserved.RATIONALE Soil water stable isotopes are a powerful tool for tracking interactions between the hydrosphere, geosphere, atmosphere, and biosphere. The challenges associated with creating high temporal resolution soil water stable isotope data sets from a diversity of sites have limited the utility of stable isotope geochemistry in addressing a range of complex problems. A device that can enable further development of higher temporal resolution soil water isotope datasets that are created with minimal soil profile disruption from remote sites would greatly expand the utility of soil water stable isotope analyses. METHODS We designed a method for sampling and storing soil water vapor for stable isotope analysis that leverages recent advances in soil water sampling strategies. Here, we test the reliability of the storage system by introducing water vapor of known oxygen and hydrogen isotopic composition into the storage system, storing the water vapor for a pre-determined amount of time, and then measuring the stable isotope composition of the vapor after the storage period. RESULTS We demonstrate that water vapor stored in our flasks reliably maintains its isotope composition within overall system uncertainty (± 0.5‰ for δ18 O values and ± 2.4‰ for δ2 H values) for up to 30 days. CONCLUSION This method has the potential to enable the collection of high temporal resolution soil water isotope data sets from remote sites that are not accessed daily in a time- and cost-effective manner. All the components used in the system can be easily controlled by open-source microcontrollers, which will be used in the future to automate sampling routines for remote field deployment. The system is designed to be an open-source tool for use by other researchers. This article is protected by copyright. All rights reserved.