Alcaligenes xylosoxidans conjunctivitis

PURPOSE: To report a case of chronic unilateral conjunctivitis caused by Alcaligenes xylosoxidans. METHODS: A previously healthy 47-year-old woman presented with left eye purulent discharge and irritation beginning 3 months earlier. The patient had previously been treated with bacitracin and olopatadine without improvement. Bacterial staining, culture, and antibiotic sensitivities were performed from a conjunctival swab. RESULTS: The cultures revealed heavy growth of A. xylosoxidans. The organism was resistant to aminoglycosides, fluoroquinolones, and cephalosporins. The patient was started on polytrim, but an allergic reaction forced the use of topical Timentin 2%. After 14 days of treatment, the infection completely resolved. CONCLUSIONS: To our knowledge, this is the first case report of an external ocular infection caused by A. xylosoxidans in a host without predisposing risk factors and the first case report of isolated conjunctivitis caused by A. xylosoxidans. A. xylosoxidans should be considered a rare but potential pathogen capable of producing chronic conjunctivitis in an otherwise healthy host.     

Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study of FGFR1 fusions in acute myeloid leukemia

The 8p11 myeloproliferative syndrome (EMS) is associated with translocations that disrupt the FGFR1 gene. To date, 8 fusion partners of FGFR1 have been identified. However, no primary leukemia cell lines were identified that contain any of these fusions. Here, we screened more than 40 acute myeloid leukemia cell lines for constitutive phosphorylation of STAT5 and applied an immunoaffinity profiling strategy to identify tyrosine-phosphorylated proteins in the KG-1 cell line. Mass spectrometry analysis of KG-1 cells revealed aberrant tyrosine phosphorylation of FGFR1. Subsequent analysis led to the identification of a fusion of the FGFR1OP2 gene to the FGFR1 gene. Small interfering RNA (siRNA) against FGFR1 specifically inhibited the growth and induced apoptosis of KG-1 cells. Thus, the KG-1 cell line provides an in vitro model for the study of FGFR1 fusions associated with leukemia and for the analysis of small molecule inhibitors against FGFR1 fusions.     

DA1 receptor mediates dopamine-induced relaxation of opossum lower esophageal sphincter in vitro

The objective of the present experiments was to determine the specific receptor subtype through which dopamine (DA) receptor agonists relax the lower esophageal sphincter in vitro. Opossum lower esophageal sphincter smooth muscle strips were placed in oxygenated Krebs' solution containing propranolol and cocaine. The tissues were placed at a tension that gave maximum relaxation to electrical field stimulation and were then pretreated with phenoxybenzamine. The effects of DA, and the DA receptor agonists epinine and apomorphine were determined. In addition, agonist responses were studied in the presence of the selective DA2 receptor antagonist domperidone, a mixed DA1/DA2 receptor antagonist metoclopramide, and the selective DA1 receptor antagonists bulbocapnine and SK&F 83566. The DA agonists relaxed the smooth muscle strips in the following order of potency: DA greater than epinine greater than apomorphine. Domperidone did not antagonize DA- or apomorphine-induced relaxation. Metoclopramide failed to alter DA-induced relaxation. Bulbocapnine and SK&F 83566 significantly inhibited the relaxation induced by DA. These data indicate that DA-induced lower esophageal sphincter relaxation in vitro is mediated by DA1 receptors.     

Interferon Gamma ELISPOT Testing as a Risk‐Stratifying Biomarker for Kidney Transplant Injury: Results From the CTOT‐01 Multicenter Study

Previous studies suggest that quantifying donor‐reactive memory T cells prior to kidney transplantation by interferon gamma enzyme‐linked immunosorbent spot assay (IFNγELISPOT) can assist in assessing risk of posttransplant allograft injury. Herein, we report an analysis of IFNγELISPOT results from the multicenter, Clinical Trials in Organ Transplantation‐01 observational study of primary kidney transplant recipients treated with heterogeneous immunosuppression. Within the subset of 176 subjects with available IFNγELISPOT results, pretransplant IFNγELISPOT positivity surprisingly did not correlate with either the incidence of acute rejection (AR) or estimated glomerular filtration rate (eGFR) at 6‐ or 12‐month. These unanticipated results prompted us to examine potential effect modifiers, including the use of T cell‐depleting, rabbit anti‐thymocyte globulin (ATG). Within the no‐ATG subset, IFNγELISPOT^neg subjects had higher 6‐ and 12‐month eGFRs than IFNγELISPOT^pos subjects, independent of biopsy‐proven AR, peak PRA, human leukocyte antigen mismatches, African‐American race, donor source, and recipient age or gender. In contrast, IFNγELISPOT status did not correlate with posttransplant eGFR in subjects given ATG. Our data confirm an association between pretransplant IFNγELISPOT positivity and lower posttransplant eGFR, but only in patients who do not receive ATG induction. Controlled studies are needed to test the hypothesis that ATG induction is preferentially beneficial to transplant candidates with high frequencies of donor‐reactive memory T cells.     

The presence of inhibitory RNA elements in the late 3'-untranslated region is a conserved property of human papillomaviruses

Here we have tested the inhibitory activity of the late untranslated region (UTR) of nine different human papillomavirus (HPV) types representing three different genera and six different species. These HPVs include both low-risk and high-risk types. We found that the late UTR of the various HPVs all displayed inhibitory activity, although they inhibited gene expression to various extent. The late UTR from the two distantly related HPV types 1 and 16, which are two different species that belong to different genera, each interacted with a 55 kDa protein. This protein cross-linked specifically to both HPV-1 and HPV-16 late UTR, although it bound more strongly to HPV-16 than to HPV-1, which correlated with the higher inhibitory activity of the HPV-16 late UTR. Mutagenesis experiments revealed that inactivation of two UGUUUGU motifs in the HPV-16 late UTR or two UAUUUAU motifs in the HPV-1 late UTR resulted in loss of binding of p55. In summary, these results demonstrate that the presence inhibitory elements encoding PuU(3-5)Pu-motifs in the HPV late UTR is a conserved property of different HPV types, species and genera, and suggest that these elements play an important role in the viral life cycle.     

Incentives and Disincentives for the Treatment of Depression and Anxiety: A Scoping Review

Objective:

There is widespread support for primary care to help address growing mental health care demands. Incentives and disincentives are widely used in the design of health care systems to help steer toward desired goals. The absence of a conceptual model to help understand the range of factors that influence the provision of primary mental health care inspired a scoping review of the literature. Understanding the incentives that promote and the disincentives that deter treatment for depression and anxiety in the primary care context will help to achieve goals of greater access to mental health care.

Method:

A review of the literature was conducted to answer the question, how are incentives and disincentives conceptualized in studies investigating the treatment of common mental disorders in primary care? A comprehensive search of MEDLINE, PsycINFO, CINAHL, and Google Scholar was undertaken using Arksey and O’Malley’s 5-stage methodological framework for scoping reviews.

Results:

We identified 27 studies. A range of incentives and disincentives influence the success of primary mental health care initiatives to treat depression and anxiety. Six types of incentives and disincentives can encourage or discourage treatment of depression and anxiety in primary care: attitudes and beliefs, training and core competencies, leadership, organizational, financial, and systemic.

Conclusions:

Understanding that there are 6 different types of incentives that influence treatment for anxiety and depression in primary care may help service planners who are trying to promote improved mental health care.