TRPA1-mediated responses in trigeminal sensory neurons: interaction between TRPA1 and TRPV1

The transient receptor potential (TRP)A1 channel is involved in the transduction of inflammation-induced noxious stimuli from the periphery. Previous studies have characterized the properties of TRPA1 in heterologous expression systems. However, there is little information on the properties of TRPA1-mediated currents in sensory neurons. A capsaicin-sensitive subset of rat and mouse trigeminal ganglion sensory neurons was activated with TRPA1-specific agonists, mustard oil and the cannabinoid WIN55,212. Mustard oil- and WIN55,212-gated currents exhibited marked variability in their kinetics of activation and acute desensitization. TRPA1-mediated responses in neurons also possess a characteristic voltage dependency with profound outward rectification that is influenced by extracellular Ca²⁺ and the type and concentration of TRPA1-specific agonists. Examination of TRPA1-mediated responses in TRPA1-containing cells indicated that the features of neuronal TRPA1 are not duplicated in cells expressing only TRPA1 and, instead, can be restored only when TRPA1 and TRPV1 channels are coexpressed. In summary, our results suggest that TRPA1-mediated responses in sensory neurons have distinct characteristics that can be accounted for by the coexpression of the TRPV1 and TRPA1 channels.     

Impact on survival of early tumor growth between surgery and radiotherapy in patients with de novo glioblastoma

Journal of Neuro-Oncology - Glioblastoma is the most aggressive malignant brain tumor. Despite multimodal treatments, median survival is only 15 months for glioblastoma patients, with...     

Systemic lupus erythematosus with optical neuromyelitis (Devic's syndrome). A case with a 35-year follow-up

Optical neuromyelitis or Devic's syndrome is a very uncommon neurological manifestation of systemic lupus erythematosus. It is also associated with antiphospholipid antibodies, limited responsiveness to glucocorticoid treatment and a poor prognosis. We report the case of a female systemic lupus erythematosus patient who developed recurrent flares of optical neuritis and transverse myelitis. These flares consistently responded to glucocorticoid therapy. Despite the absence of overt anticardiolipin antibodies in the course of the disease, long-term anticoagulant therapy has been introduced with positive results. Treatments are usually of limited efficacy in Devic's syndrome. In our patient, however, aggressive glucocorticoid treatment resulted in prolonged survival.     

HPV Vaccine and Latino Immigrant Parents: If They Offer It,We Will Get It

HPV vaccination rates remain low in the fast growing Latino children population while we continue to observe large HPV-associated cancer disparities in the Latino population. In this study, we sought to elucidate Latino immigrant parents’ barriers to obtaining the HPV vaccine for their children. Five focus groups were conducted with Latino immigrant parents of minors (i.e., 9–17 year old) who had not yet initiated the HPV vaccine series. Three major findings were identified from the focus groups: (1) low levels of awareness and knowledge of HPV and the HPV vaccine, (2) high confidence that parent can get the vaccine for their eligible child and (3) lack of provider recommendation as the main barrier to vaccination. Children of Latino immigrant parents could benefit from increased provider recommendation for the HPV vaccine while providing tailored HPV information to parents.     

Population level outcomes and cost‐effectiveness of hepatitis C treatment pre‐ vs postkidney transplantation

Direct‐acting antivirals approved for use in patients with end‐stage renal disease (ESRD) now exist. HCV‐positive (HCV+) ESRD patients have the opportunity to decrease the waiting times for transplantation by accepting HCV‐infected kidneys. The optimal timing for HCV treatment (pre‐ vs posttransplant) among kidney transplant candidates is unknown. Monte Carlo microsimulation of 100 000 candidates was used to examine the cost‐effectiveness of HCV treatment pretransplant vs posttransplant by liver fibrosis stage and waiting time over a lifetime time horizon using 2 regimens approved for ESRD patients. Treatment pretransplant yielded higher quality‐adjusted life years (QALYs) compared with posttransplant treatment in all subgroups except those with Meta‐analysis of Histological Data in Viral Hepatitis stage F0 (pretransplant: 5.7 QALYs vs posttransplant: 5.8 QALYs). However, treatment posttransplant was cost‐saving due to decreased dialysis duration with the use of HCV‐infected kidneys (pretransplant: $735 700 vs posttransplant: $682 400). Using a willingness‐to‐pay threshold of $100 000, treatment pretransplant was not cost‐effective except for those with Meta‐analysis of Histological Data in Viral Hepatitis stage F3 whose fibrosis progression was halted. If HCV+ candidates had access to HCV‐infected donors and were transplanted ≥9 months sooner than HCV‐negative candidates, treatment pretransplant was no longer cost‐effective (incremental cost‐effectiveness ratio [ICER]: $107 100). In conclusion, optimal timing of treatment depends on fibrosis stage and access to HCV+ kidneys but generally favors posttransplant HCV eradication.     

Guidelines for visualization and analysis of DC in tissues using multiparameter fluorescence microscopy imaging methods

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various non-lymphoid tissues. Here, we provide detailed procedures for a variety of multiparameter fluorescence microscopy imaging methods to explore the spatial organization of DC in tissues and to dissect how DC migrate, communicate, and mediate their multiple functional roles in immunity in a variety of tissue settings. The protocols presented here entail approaches to study DC dynamics and T cell cross-talk by intravital microscopy, large-scale visualization, identification, and quantitative analysis of DC subsets and their functions by multiparameter fluorescence microscopy of fixed tissue sections, and an approach to study DC interactions with tissue cells in a 3D cell culture model. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer-reviewed by leading experts and approved by all co-authors, making it an essential resource for basic and clinical DC immunologists.     

Salmonella infection after anterior cruciate ligament reconstruction: A case report

BACKGROUNDInfections after anterior cruciate ligament reconstruction (ACLR) are rare. No cases of Salmonella infection have been described to our knowledge.CASE SUMMARYWe describe a rare case of Salmonella infection in a 23-year-old patient following an ACLR. The patient presented with subacute septic arthritis, 26 d after a hamstring autograft ACLR. The pathogen, Salmonella enterica typhimurium was isolated by bacteriological sampling of the first arthroscopic lavage. Two arthroscopic lavages were required, with intravenous antibiotic therapy for two weeks with cefotaxime and ciprofloxacin, followed by oral antibiotics with amoxicillin and ciprofloxacin for a total duration of three months. This approach treated the infection but two years after the septic arthritis, faced with ongoing knee instability due to graft damage, a revision ACLR with a bone-tendon-bone graft was performed. At the last follow-up, full range of knee motion had been achieved and sports activities resumed.CONCLUSIONInfection after ACLR is rare and requires an early diagnosis and management in order to treat the infection and prevent arthritis-related joint cartilage destruction and damage to the graft.     

Compatibility of Lactated Ringer’s Injection With 94 Selected Intravenous Drugs During Simulated Y-site Administration

Objective: To test the compatibility of intravenous (IV) lactated Ringer’s injection (LR) with 94 injectable (IV) drugs during simulated Y-site administration. Methods: Ninety-four IV drugs were investigated for compatibility with LR (Baxter). Each sample was prepared in duplicate and performed at room temperature. Two observers performed visual evaluation independently immediately upon mixing and then 15 minutes, 1 hour, 2 hours, 3 hours, and 4 hours after admixture. Another observer performed a particle counting test on 1 of the 2 duplicates of each admixture that did not immediately show incompatibility and then after 4 hours by a light obscuration particle count test. Results: Of the 94 tested drugs, 86 were found to be compatible with LR. A total of 8 drugs were found to be physically incompatible. Of these incompatible drugs, 7 were directly identified visually and 1 was confirmed by the light obscuration particle count test. Conclusion: Lactated Ringer’s injection was physically compatible for 4 hours with 86 tested drugs during simulated Y-site administration. Eight drugs, ciprofloxacin, cyclosporine, diazepam, ketamine, lorazepam, nitroglycerin, phenytoin, and propofol, were found to be incompatible and should not be administered with LR.