Simeprevir added to peginterferon and ribavirin lessens time with fatigue,depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST‐1, QUEST‐2 and PROMISE studies

The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient‐reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES‐D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double‐blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response‐guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline–Week 60, AUC₆₀) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post‐treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR‐related AEs without adding to AE severity.     

Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.     

The tragic fate of group 3 innate lymphoid cells during HIV-1 infection

HIV-1 infection usually leads to systemic chronic inflammation that is associated with gut microbial translocation. The recently defined group 3 innate lymphoid cells (ILC3s) are critical for maintenance of intestinal barrier function; however, it is not clear whether and how HIV-1 infection influences the function of these cells. In this issue of the JCI, Zhang and colleagues present compelling evidence that the survival and function of ILC3s are dramatically impaired by HIV-1 infection. The authors provide evidence that HIV-1 infection induces persistent activation of plasmacytoid dendritic cells (pDCs) and production of type I IFNs, which together increase expression of death receptor CD95 on ILC3s and thereby promote subsequent ILC3 apoptosis. Together, these results identify a mechanism that explains the impaired intestinal barrier function that results from chronic HIV-1 infection and shed light on the role of pDCs in HIV-1 immunopathogenesis and therapy.     

Psychosocial mechanisms of a behavioral treatment for urinary incontinence of prostate cancer survivors

Abstract

Purpose: We examined underlying psychosocial processes of a behavioral treatment for urinary incontinence (UI) of prostate cancer survivors.

Design: Secondary analysis of data collected from a clinical trial.

Sample: Two hundred forty-four prostate cancer survivors who participated in a clinical trial of behavioral intervention to UI as intervention or control subjects.

Methods: The participants had a 3-month behavioral intervention or usual care and were followed up for an additional 3?months. They were assessed at baseline, 3, and 6?months. Latent growth curve models were performed to examine trajectories of each study variable and relationships among the variables.

Findings: Increasing self-efficacy and social support were significantly and independently associated with more reduction of urinary leakage frequency over time.

Implications for psychosocial oncology: Providing problem-solving skills and social support, including peer support, are essential for empowering patients to reduce UI.     

A Stable Q Compensated Reverse Time Migration Method Based on Excitation Amplitude Imaging Condition

The stability and efficiency, especially the stability, are generally concerned issues in Q compensated reverse time migration (Q-RTM). The instability occurs because of the exponentially boosted high frequency ambient noise during the forward or backward seismic wavefield propagation. The regularization and low-pass filtering methods are two effective strategies to control the instability of the wave propagation in Q-RTM. However, the regularization parameters are determined experimentally, and the wavefield cannot be recovered accurately. The low-pass filtering method cannot balance the selection of cutoff frequency for varying Q values, and may damage the effective signals, especially when the signal-to-noise ratio (SNR) of the seismic data is low, the Q-RTM will be a highly unstable process. In order to achieve the purpose of stability, the selection of cutoff frequency will be small enough, which can cause great damage to the effective high frequency signals. In this paper, we present a stable Q-RTM algorithm based on the excitation amplitude imaging condition, which can compensate both the amplitude attenuation and phase dispersion. Unlike the existing Q-RTM algorithms enlarging the amplitude, the exponentially attenuated seismic wavefield will be used during both the forward and backward wavefield propagation of Q-RTM. Therefore, the new Q-RTM algorithm is relative stable, even for the low SNR seismic data. In order to show the accuracy and stability of our stable Q-RTM algorithm clearly, an example based on Graben model will be illustrated. Then, a realistic BP gas chimney model further demonstrates that the proposed method enjoys good stability and anti-noise performance compared with the traditional Q-RTM with amplitude amplification. Compare the Q-RTM images of these two models to the reference images obtained by the acoustic RTM with acoustic seismic data, the new Q-RTM results match the reference images quite well. The proposed method is also tested using a field seismic data, the result shows the effectiveness of our proposed method.