B cell antigen receptor expression and phosphatidylinositol 3-kinase signaling regulate genesis and maintenance of mouse chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a frequent lymphoproliferative disorder of B cells. Although inhibitors targeting signal proteins involved in B cell antigen receptor (BCR) signaling constitute an important part of the current therapeutic protocols for CLL patients, the exact role of BCR signaling, as compared to genetic aberration, in the development and progression of CLL is controversial. To investigate whether BCR expression per se is pivotal for the development and maintenance of CLL B cells, we used the TCL1 mouse model. By ablating the BCR in CLL cells from TCL1 transgenic mice, we show that CLL cells cannot survive without BCR signaling and are lost within eight weeks in diseased mice. Furthermore, we tested whether mutations augmenting B cell signaling influence the course of CLL development and its severity. The Phosphatidylinositol-3-kinase (PI3K) signaling pathway is an integral part of the BCR signaling machinery and its activity is indispensable for B cell survival. It is negatively regulated by the lipid phosphatase PTEN, whose loss mimics PI3K pathway activation. Herein, we show that PTEN has a key regulatory function in the development of CLL, as deletion of the Pten gene resulted in greatly accelerated onset of the disease. By contrast, deletion of the gene TP53, which encodes the tumor suppressor p53 and is highly mutated in CLL, did not accelerate disease development, confirming that development of CLL was specifically triggered by augmented PI3K activity through loss of PTEN and suggesting that CLL driver consequences most likely affect BCR signaling. Moreover, we could show that in human CLL patient samples, 64% and 81% of CLL patients with a mutated and unmutated IgH VH, respectively, show downregulated PTEN protein expression in CLL B cells if compared to healthy donor B cells. Importantly, we found that B cells derived from CLL patients had higher expression levels of the miRNA-21 and miRNA-29, which suppresses PTEN translation, compared to healthy donors. The high levels of miRNA-29 might be induced by increased PAX5 expression of the B-CLL cells. We hypothesize that downregulation of PTEN by increased expression levels of miR-21, PAX5 and miR-29 could be a novel mechanism of CLL tumorigenesis that is not established yet. Together, our study demonstrates the pivotal role for BCR signaling in CLL development and deepens our understanding of the molecular mechanisms underlying the genesis of CLL and for the development of new treatment strategies

Arabic version of the SF-Qualiveen: cross-cultural adaptation, translation, and validation of urinary disorder‐specific instruments in patients with multiple sclerosis

Abstract Background The Short Form Qualiveen (SF-Qualiveen) questionnaire assesses the effect of bladder and urinary symptoms on patients’ quality of life (QoL) with urological impairment caused by neurological diseases. There is no validated SF-Qualiveen questionnaire in Arabic, so this study aims to provide a translated and validated version of the SF-Qualiveen questionnaire among Arabic-speaking patients with multiple sclerosis (MS). Methods The English version of the SF-Qualiveen was translated into Arabic using an algorithm for linguistic and cultural adaptation. MS patients completed the SF-Qualiveen, and the Neurogenic Bladder Symptom Score(NBSS) questionnaire. Psychometric features such as content and construct validity, test–retest reliability, and internal consistency were analyzed. Construct validity was evaluated by contrasting the SF-Qualiveen with the NBSS questionnaire. Internal consistency was measured using Cronbach’s alpha, whereas the intraclass correlation coefficient (ICC) was employed to assess the test-retest reliability. Results One hundred and two patients with MS were included in this study. The internal consistency of the total SF-Qualiveen, and the domains “Bother with limitations,” “Fear,” “Feeling,” and “Frequency of limitations” showed good internal consistency (Cronbach’s alpha of > 0.7). ICC was 0.91 for the total score 0.85 for the Bother with limitations, 0.81 for Fears, 0.86 for Feeling, and 0.81 for Frequency of limitations. The correlation analysis revealed a positive association between the total scores on the NBSS and the domains of the SF-Qualiveen, comprising bother with limitations (r = 0.473, p = 0.027), fears (r = 0.611, p = 0.031), feelings (r = 0.572, p = 0.04), and frequency of limitations (r = 0.514, p = 0.013). Conclusions The findings of this validation study revealed that the SF-Qualiveen is a reliable and valid instrument appropriate for Arabic-speaking patients with MS in both research and clinical practice

Impact of the COVID-19 pandemic on the quality of life and accessing rehabilitation services among patients with spinal cord injury and their fear of COVID-19

Abstract Background The unanticipated coronavirus disease (COVID-19) had a negative effect on the quality of life (QoL) of patients with spinal cord injury (SCI) and made significant changes in their daily routine. Patients with SCI face additional health risks, especially mental, behavioral, and physical. Without regular physiotherapy sessions, patients' psychological and functional abilities can deteriorate, and complications can occur. There is little information available about the impact of COVID-19 on the quality of life of patients with SCI, and their access to rehabilitation services during the pandemic. Objective This study was designed to examine the effects of the COVID-19 pandemic on the quality of life of patients with SCI and also their fear of COVID-19. The pandemic’s impact on the accessibility of rehabilitation services and attendance at physiotherapy sessions in one Chinese hospital were also documented. Design An observational study based on an online survey. Setting Outpatients clinic at the rehabilitation department of Wuhan's Tongji Hospital. Participants People who had been diagnosed with a spinal cord injury (SCI) and who were receiving regular medical monitoring as outpatients at the rehabilitation department were invited to participate in our study (n = 127). Intervention Not applicable. Outcome measures A 12-Item Short-Form Health Survey (SF-12) designed to measure participants' quality of life before and during the pandemic. Their fear of COVID-19 was quantified using the Fear of COVID-19 Scale (FCV-19S). Demographic and medical status information was extracted from their medical records. Their use of rehabilitation services and attendance at physical therapy sessions was also documented. Results Seventy-nine patients with SCI completed the SF-12 and FCV-19 scale. The mental and physical aspects of the participants’ quality of life declined significantly, during the epidemic compared to the pre-epidemic period. More than half of the participants have experienced fear of COVID-19 based on FCV-19S. Most received only irregular physical therapy during routine checkups. Worry about virus transmission was the most common cause cited for not attending regular physical therapy sessions. Conclusions The quality of life of these Chinese patients with SCI declined during the pandemic. Most of the participants were shown a high level of fear of COVID-19 and were classified as having an intense fear of COVID-19, in addition to the impact of the pandemic on their access to rehabilitation services and attendance at physical therapy sessions

Brillouin distributed fiber sensor based on a Dual-frequency laser

International audienc

Measurement of Brillouin gain spectrum with dual-frequency laser for optical fibre sensor

International audienceIn this paper, we present a first measurement of Brillouin gain spectrum with dual-frequency solid-state laser. This allows a coherent detection of the Brillouin backscattered spectrum in a frequency range below the hundreds of MHz by fine tuning of the difference between the two cross-polarized fields emitted by the laser. The photodetection at low frequency benefits from the balanced detection technique where high dynamic range measurements are largely available. The narrow linewidth of the cross-polarized filed permits also the direct measurement of the Brillouin spectrum linewidth. The system is demonstrated by measuring the Brillouin frequency shift with temperature when standard single-mode fiber (SMF-28) and large effective area fiber (LEAF) are fully heated. This gives temperature coefficients close to theoretical expectations with values of 1.16 MHz/°C for SMF-28 and 1.15 MHz/°C for LEAF

Apport de la fibre optique pour l’étude des ancrages passifs scellés au rocher en milieu fracturé

International audienceLa fracturation des massifs rocheux impacte le comportement des ancrages passifs scellés au rocher utilisés pour la gestion du risque rocheux. Nous présentons les résultats d’essais d’arrachement instrumentés par fibre optique réalisés sur trois sites présentant des niveaux de fracturation variables. Ces résultats couplés avec de l’endoscopie permettent de mieux comprendre les sollicitations en profondeur