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  • Jorgensen Lutz posted an update 2 days, 6 hours ago

    OBJECTIVE Neuronal loss in the substantia nigra pars compacta (SNpc) in Parkinson disease (PD) is not uniform, as dopamine neurons from the ventral tier are lost more rapidly than those of the dorsal tier. Identifying the intrinsic differences that account for this differential vulnerability may provide a key for developing new treatments for PD. METHODS Here, we compared the RNA-sequenced transcriptomes of ~100 laser captured microdissected SNpc neurons from each tier from 7 healthy controls. RESULTS Expression levels of dopaminergic markers were similar across the tiers, whereas markers specific to the neighboring ventral tegmental area were virtually undetected. After accounting for unwanted sources of variation, we identified 106 differentially expressed genes (DEGs) between the SNpc tiers. Selleck Tucidinostat The genes higher in the dorsal/resistant SNpc tier neurons displayed coordinated patterns of expression across the human brain, their protein products had more interactions than expected by chance, and they demonstrated evidence of functional convergence. No significant shared functionality was found for genes higher in the ventral/vulnerable SNpc tier. Surprisingly but importantly, none of the identified DEGs was among the familial PD genes or genome-wide associated loci. Finally, we found some DEGs in opposite tier orientation between human and analogous mouse populations. INTERPRETATION Our results highlight functional enrichments of vesicular trafficking, ion transport/homeostasis and oxidative stress genes showing higher expression in the resistant neurons of the SNpc dorsal tier. Furthermore, the comparison of gene expression variation in human and mouse SNpc populations strongly argues for the need of human-focused omics studies. ANN NEUROL 2020. © 2020 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.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).

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