Complement Inhibition Promotes Endogenous Neurogenesis and Sustained Anti-Inflammatory Neuroprotection following Reperfused Stroke

The restoration of blood-flow following cerebral ischemia incites a series of deleterious cascades that exacerbate neuronal injury. Pharmacologic inhibition of the C3a-receptor ameliorates cerebral injury by attenuating post-ischemic inflammation. Recent reports also implicate C3a in the modulation of tissue repair, suggesting that complement may influence both injury and recovery at later post-ischemic time-points.To evaluate the effect of C3a-receptor antagonism on post-ischemic neurogenesis and neurological outcome in the subacute period of stroke, transient focal cerebral ischemia was induced in adult male C57BL/6 mice treated with multiple regimens of a C3a receptor antagonist (C3aRA).Low-dose C3aRA administration during the acute phase of stroke promotes neuroblast proliferation in the subventricular zone at 7 days. Additionally, the C3a receptor is expressed on T-lymphocytes within the ischemic territory at 7 days, and this cellular infiltrate is abrogated by C3aRA administration. Finally, C3aRA treatment confers robust histologic and functional neuroprotection at this delayed time-point.Targeted complement inhibition through low-dose antagonism of the C3a receptor promotes post-ischemic neuroblast proliferation in the SVZ. Furthermore, C3aRA administration suppresses T-lymphocyte infiltration and improves delayed functional and histologic outcome following reperfused stroke. Post-ischemic complement activation may be pharmacologically manipulated to yield an effective therapy for stroke

Transcriptional analysis of susceptible and resistant European corn borer strains and their response to Cry1F protoxin

Background: Despite a number of recent reports of insect resistance to transgenic crops expressing insecticidal toxins from Bacillus thuringiensis (Bt), little is known about the mechanism of resistance to these toxins. The purpose of this study is to identify genes associated with the mechanism of Cry1F toxin resistance in European corn borer (Ostrinia nubilalis Hübner). For this, we compared the global transcriptomic response of laboratory selected resistant and susceptible O. nubilalis strain to Cry1F toxin. We further identified constitutive transcriptional differences between the two strains. Results: An O. nubilalis midgut transcriptome of 36,125 transcripts was assembled de novo from 106 million Illumina HiSeq and Roche 454 reads and used as a reference for estimation of differential gene expression analysis. Evaluation of gene expression profiles of midgut tissues from the Cry1F susceptible and resistant strains after toxin exposure identified a suite of genes that responded to the toxin in the susceptible strain (n = 1,654), but almost 20-fold fewer in the resistant strain (n = 84). A total of 5,455 midgut transcripts showed significant constitutive expression differences between Cry1F susceptible and resistant strains. Transcripts coding for previously identified Cry toxin receptors, cadherin and alkaline phosphatase and proteases were also differentially expressed in the midgut of the susceptible and resistant strains. Conclusions: Our current study provides a valuable resource for further molecular characterization of Bt resistance and insect response to Cry1F toxin in O. nubilalis and other pest species

Music Listening Among Postoperative Patients in the Intensive Care Unit: A Randomized Controlled Trial with Mixed-Methods Analysis

Background: Music listening may reduce the physiological, emotional, and mental effects of distress and anxiety. It is unclear whether music listening may reduce the amount of opioids used for pain management in critical care, postoperative patients or whether music may improve patient experience in the intensive care unit (ICU). Methods: A total of 41 surgical patients were randomized to either music listening or controlled non-music listening groups on ICU admission. Approximately 50-minute music listening interventions were offered 4 times per day (every 4-6 hours) during the 48 hours of patients’ ICU stays. Pain, distress, and anxiety scores were measured immediately before and after music listening or controlled resting periods. Total opioid intake was recorded every 24 hours and during each intervention. Results: There was no significant difference in pain, opioid intake, distress, or anxiety scores between the control and music listening groups during the first 4 time points of the study. However, a mixed modeling analysis examining the pre- and post-intervention scores at the first time point revealed a significant interaction in the Numeric Rating Scale (NRS) for pain between the music and the control groups ( P  = .037). The Numeric Rating Score decreased in the music group but remained stable in the control group. Following discharge from the ICU, the music group’s interviews were analyzed for themes. Conclusions: Despite the limited sample size, this study identified music listening as an appropriate intervention that improved patients’ post-intervention experience, according to patients’ self-report. Future mixed methods studies are needed to examine both qualitative patient perspectives and methodology to improve music listening in critical care units

Pharmacokinetics of Anidulafungin in Pleural Fluid during the Treatment of a Patient with Candida Empyema▿

Candida empyema is a serious complication of disseminated candidiasis. However, little is known about the intrapleural pharmacokinetics of echinocandins. We report the penetration of anidulafungin into the pleural fluid of a patient with Candida tropicalis empyema. The anidulafungin ratio for the area under the concentration-time curve from 0 h to the last measurement between pleural fluid and serum values was only 0.125 (12.5%), with pleural fluid concentrations ranging between 0.67 and 0.88 μg/ml

Aspergillus arthritis: analysis of clinical manifestations, diagnosis, and treatment of 31 reported cases

Aspergillus arthritis is a debilitating form of invasive aspergillosis. Little is known about its epidemiology, clinical manifestations, laboratory features, treatment, and prognosis. Cases of Aspergillus arthritis were reviewed in the English literature from 1967 through 2015 for variables of arthritis with Aspergillus spp. recovered from joint and/or adjacent bone, underlying conditions, symptoms, signs, inflammatory biomarkers, diagnostic imaging, management, and outcome. Among 31 evaluable cases, 87% were males and 13% pediatric. Median age was 50 y (range 1-83 y). Seventeen (55%) patients were immunosuppressed with such conditions as hematological malignancies (26%), corticosteroids (39%), and/or transplantation (26%). Approximately one-half (52%) of patients had hematogenous seeding of the joint, and more than 80% had de novo infection with no prior antifungal therapy. Oligoarticular infection (2-3 joints) occurred in 45% and contiguous osteomyelitis was present in 61%. Clinical manifestations included pain (87%), edema (26%), and limited function (23%), with knees (35%), intervertebral discs (26%), and hips (16%) being most commonly infected. Aspergillus fumigatus constituted 77% of cases followed by Aspergillus flavus in 13%, Aspergillus niger in 3%, and not specified in 7%. Median ESR was 90 mm/hr and median CRP was 3.6 mg/dl. Median synovial fluid WBC was 17,200/mu L (7,300-128,000) with 72% PMNs (range 61-92). Osteolysis occurred in 35%, and soft-tissue extension 47%. Nineteen patients (61%) were managed with combined medical and surgical therapy, 10 (32%) with medical therapy only, and 2 (6%) surgery only. Amphotericin B and itraconazole were the most frequently used agents with median duration of therapy of 219 days (range 30-545). Surgical interventions included debridement in 61%, drainage 19%, and amputation 6%. Complete or partial response was achieved in 71% and relapse occurred in 16%. Medical therapy was reinstituted with successful outcome in these patients. Overall survival was 65%. Aspergillus arthritis mainly develops as a de novo infection involving knees and intervertebral disks in immunocompromised patients with localizing symptoms. Contiguous osteomyelitis is frequently observed. Diagnosis is established by synovial fluid culture. Aspergillus arthritis is therapeutically challenging with most patients undergoing surgery and protracted antifungal therapy