1,044 research outputs found

    Tool For Managing File Ownership and Permissions For Online Storage Services

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    It is difficult and time-consuming for users of online file storage and sharing services to view and manage file permissions for the files that are stored and/or shared via such platforms. No easy mechanisms are available to see how a file is being shared without diving into each file individually. This disclosure describes a sharing visibility tool that enables users to see how their files are being shared via an online file sharing service and to manage file permissions individually or in bulk. With user permission, the tool utilizes application programming interfaces (APIs) provided by online file sharing services to access the user’s files. The tool provides a user interface that enables users to view and modify file permissions, transfer file ownership, verify that file permissions have been audited, etc

    Retinal arteriolar vascular reactivity in untreated and progressive primary open-angle glaucoma

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    PURPOSE. To determine (1) the magnitude of retinal arteriolar vascular reactivity to normoxic hypercapnia in patients with untreated primary open-angle glaucoma (uPOAG) or progressive (p)POAG and in control subjects and (2) the effect of treatment with 2% dorzolamide on retinal vascular reactivity in uPOAG. METHODS. The sample comprised 11 patients with uPOAG (after undergoing treatment, they became treated (t)POAG), 17 patients with pPOAG (i.e., manifesting optic disc hemorrhage), and 17 age-similar control subjects. The partial pressure of end-tidal CO 2 (PETCO 2 ) was stabilized at 38 mm Hg at baseline. After baseline (10 minutes), normoxic hypercapnia was then induced (15 minutes) with an automated gas flow controller. Retinal arteriolar and optic nerve head (ONH) blood hemodynamics were assessed. The procedures were repeated after treatment with 2% dorzolamide for 2 weeks in tPOAG. RESULTS. Baseline arteriolar hemodynamics were not different across the groups. In control subjects, diameter, velocity, and flow increased (P Ͻ 0.001) in response to normoxic hypercapnia. There was no change in all three hemodynamic parameters to normoxic hypercapnia in uPOAG, whereas only blood flow increased (P ϭ 0.030) in pPOAG. Vascular reactivity was decreased in uPOAG and pPOAG patients compared with that in control subjects. After treatment with topical 2% dorzolamide for 2 weeks, the tPOAG group showed an increase in diameter, velocity, and flow (P Յ 0.04) in response to normoxic hypercapnia. Similar trends were noted for ONH vascular reactivity. CONCLUSIONS. A reduced magnitude of arteriolar vascular reactivity in response to normoxic hypercapnia was shown in uPOAG and in pPOAG. Vascular reactivity improved after dorzolamide treatment in POAG. (Invest Ophthalmol Vis Sci

    IFNβ Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury.

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    Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects. We find in vivo that IFNβ mRNA is significantly increased in HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week intranasal IFNβ treatment of HIVgp120tg mice starting at 3.5 months of age increases expression of CCL4 and concomitantly protects neuronal dendrites and pre-synaptic terminals in cortex and hippocampus from gp120-induced damage. Moreover, in vivo and in vitro data suggests astrocytes are a major source of IFNβ-induced CCL4. Altogether, our results suggest exogenous IFNβ as a neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced brain injury

    Budesonide Oral Suspension Improves Symptomatic, Endoscopic, and Histologic Parameters Compared With Placebo in Patients With Eosinophilic Esophagitis

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    BACKGROUND & AIMS: Pharmacologic treatment of eosinophilic esophagitis (EoE) is limited to off-label use of corticosteroids not optimized for esophageal delivery. We performed a randomized, controlled phase 2 trial to assess the ability of budesonide oral suspension (BOS), a novel muco-adherent topical steroid formulation, to reduce symptoms and esophageal eosinophilia in adolescents and adults with EoE. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, 93 EoE patients between the ages of 11 and 40 years with dysphagia and active esophageal eosinophilia were randomized to receive either BOS 2 mg or placebo twice daily for 12 weeks. Co-primary outcomes were change in Dysphagia Symptom Questionnaire (DSQ) score from baseline, and proportion of patients with a histologic response (≤6 eosinophils/high-power field) after treatment. Endoscopic severity scores and safety parameters were assessed. RESULTS: At baseline, mean DSQ scores were 29.3 and 29.0, and mean peak eosinophil counts were 156 and 130 per hpf in the BOS and placebo groups, respectively. After treatment, DSQ scores were 15.0 and 21.5, and mean peak eosinophil counts were 39 and 113 per high-power field, respectively (P < .05 for all). For BOS vs placebo, change in DSQ score was -14.3 vs -7.5 (P = .0096), histologic response rates were 39% vs 3% (P < .0001), and change in endoscopic severity score was -3.8 vs 0.4 (P < .0001). Adverse events were similar between groups. CONCLUSIONS: Treatment with BOS was well tolerated in adolescent and young adult patients with EoE and resulted in improvement in symptomatic, endoscopic, and histologic parameters using validated outcome instruments. ClinicalTrials.gov ID NCT01642212

    The Effect of Subsidence on Segmental and Global Lordosis at Long-term Follow-up After Anterior Cervical Discectomy and Fusion

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    Objective Subsidence following anterior cervical discectomy and fusion (ACDF) may lead to disruptions of cervical alignment and lordosis. The purpose of this study was to evaluate the effect of subsidence on segmental, regional, and global lordosis. Methods This was a retrospective cohort study performed between 2016–2021 at a single institution. All measurements were performed using lateral cervical radiographs at the immediate postoperative period and at final follow-up greater than 6 months after surgery. Associations between subsidence and segmental lordosis, total fused lordosis, C2–7 lordosis, and cervical sagittal vertical alignment change were determined using Pearson correlation and multivariate logistic regression analyses. Results One hundred thirty-one patients and 244 levels were included in the study. There were 41 one-level fusions, 67 two-level fusions, and 23 three-level fusions. The median follow-up time was 366 days (interquartile range, 239–566 days). Segmental subsidence was significantly negatively associated with segmental lordosis change in the Pearson (r = -0.154, p = 0.016) and multivariate analyses (beta = -3.78; 95% confidence interval, -7.15 to -0.42; p = 0.028) but no associations between segmental or total fused subsidence and any other measures of cervical alignment were observed. Conclusion We found that subsidence is associated with segmental lordosis loss 6 months following ACDF. Surgeons should minimize subsidence to prevent long-term clinical symptoms associated with poor cervical alignment

    A multicenter study of lamivudine treatment in 33 patients with hepatitis B after liver transplantation

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    Hepatitis B virus (HBV) infection after liver transplantation (LT) may lead to severe and rapidly progressive graft failure. Antiviral treatment may be of benefit in selected patients with recurrent hepatitis B post-LT. The aim of this prospective open-label study is to determine the safety and efficacy of lamivudine in 33 liver transplant recipients with active HBV infection. The median time from LT to study enrollment was 51 months, all patients were hepatitis B surface antigen positive, and 75% and 94% of subjects had detectable hepatitis B e antigen (HBeAg) and HBV DNA at entry, respectively. The median duration of lamivudine treatment on study was 85 weeks, during which time median HBV DNA levels became undetectable by 16 weeks and 9% of patients lost previously detectable HBeAg. Serum alanine aminotransferase (ALT) levels improved in most patients and normalized in 27% of patients with elevated values pretreatment. Serum bilirubin and albumin levels significantly improved in patients with abnormal values at entry ( P < .05). Virological breakthrough was detected in 13 subjects after a median of 61 weeks of lamivudine treatment and was confirmed to be caused by YMDD mutants in all patients tested. None of the patients with virological breakthrough showed a complete loss of clinical response to lamivudine. Serum ALT and bilirubin levels in patients with and without virological breakthrough were not significantly different at last study follow-up. Study results show that lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B. However, the high rate of virological breakthrough with prolonged therapy indicates the need for further studies of combination antiviral therapy in this patient population. Our results and others further establish the improving long-term outcomes with LT for patients with hepatitis B through advances in prevention of reinfection, as well as the availability of safe and effective antiviral therapies to treat patients with HBV recurrence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35276/1/500070605_ftp.pd

    Hyperimmune anti-HBs plasma as alternative to commercial immunoglobulins for prevention of HBV recurrence after liver transplantation

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    BACKGROUND: Hepatitis B immune globulins (HBIG) in combination with nucleos(t)ide analogues (NA) are effectively used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, associated treatment costs for HBIG are exceedingly high. METHODS: Fresh frozen plasma obtained from blood donors with high anti-HBs levels (hyperimmune plasma, HIP) containing at least 4,500 IU anti-HBs was used as alternative treatment for HBV recurrence prophylaxis post-LT. RESULTS: Twenty-one HBV-related LT recipients received HIP starting at transplantation, followed by long-term combination treatment with NA. Mean follow-up time was 4.5 years (range 0.5-12.6) and each patient received on average 8.2 HIP per year (range 5.8-11.4). Anti-HBs terminal elimination kinetic after HIP administration was 20.6 days (range 13.8-30.9), which is comparable to values reported for commercial HBIG products. All 21 patients remained free of HBV recurrence during follow-up and no transfusion-transmitted infection or other serious complication was observed. Seven patients developed reversible mild transfusion reactions. The cost for one HIP unit was USD 140; average yearly HBIG treatment cost was USD 1,148 per patient, as compared to USD 25,000-100,000 for treatment with commercial HBIG. CONCLUSION: The results of this study suggest that the use of HIP may be a useful and economical approach for the prevention of HBV recurrence post-LT if used in combination with NA. Additional prospective controlled studies in larger populations are needed to confirm these results
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