HOXA4 induces expansion of hematopoietic stem cells in vitro and confers enhancement of pro-B-cells in vivo

Members of the homeobox (Hox) gene family are known to mediate expansion of hematopoietic stem cells (HSCs) and progenitors. The absence of oncogenic properties promoted HOXB4 as prime candidate in the quest to expand HSCs for clinical purposes. Despite its potential to expand HSCs, studies with mutant mice showed that Hoxb4 is not essential for HSC generation and function under physiological conditions. Expression studies and the existence of functional redundancy in particular between paralog Hox genes suggest that HOXA4 might have potent properties to expand HSCs. Here we measured the ability of HOXA4 to promote ex vivo expansion of HSCs and progenitors using retrovirus-mediated overexpression. Our results provide evidence that HOXA4-transduced HSCs and primitive progenitors expand in culture conditions and demonstrate that the potential of expanded HOXA4 HSCs to give rise to mature myeloid and lymphoid progeny in normal proportions remained intact. Interestingly, constitutive overexpression of HOXA4 resulted in an unbalanced expansion of lymphoid/myeloid progenitors in bone marrow chimeras favorable to B-cell progenitors responsive to interleukin-7. This expansion was specific for these progenitors and not for the more primitive Whitlock-Witte-initiating cells. These data indicate that early stages of B-cell development associated with proliferation are in particular sensitive to HOXA4. Thus, this study supports the potential use of HOXA4 to expand both HSCs and B-cell progenitor populations for therapeutic strategies.     

Hémodialyse continue avec membrane super high-flux au cours d’un choc septique : application clinique

Continuous renal replacement therapy (CRRT) with a high cutoff (HCO) membrane is proposed for septic shock as a blood purification technique. The aim of this therapy is to modulate the immune response through the increase of the clearances of the inflammatory mediators as compared to standard CRRT. The use of HCO membranes in daily clinical practice is limited due to the related theoretical albumin loss. Super high-flux (SHF) membranes have an optimized cutoff and, when used in a diffusive mode, may allow for high clearances of middle molecules with limited albumin loss. We report the case of a patient with pneumonia and septic shock treated with continuous hemodialysis with a SHF membrane in order to present the clinical application of this new extracorporeal blood purification technique.     

Artery phantoms for intravascular optical coherence tomography: healthy arteries

We present a method to make phantoms of coronary arteries for intravascular optical coherence tomography (IV-OCT). The phantoms provide a calibrated OCT response similar to the layered structure of arteries. The optical properties of each layer are achieved with specific concentrations of alumina and carbon black in a silicone matrix. This composition insures high durability and also approximates the elastic properties of arteries. The phantoms are fabricated in a tubular shape by the successive deposition and curing of liquid silicone mixtures on a lathe setup.     

Impact of a Program for the Management of Aggressive Behaviors on Seclusion and Restraint Use in Two High-Risk Units of a Mental Health Institute

The Omega Program for the Management of Aggressive Behaviors aims to reduce patients’ dangerous behaviors, towards themselves or others, and to reduce the use of seclusion and restraint (S/R). A previous study in a Mental Health Institute (Montreal, Canada) showed that implementing this program allowed employees of the intensive care and emergency units to gain confidence in coping with patients’ aggressions and to reduce their psychological distress. The present study, conducted in the same high-risk units, assesses the effect of the program on S/R use. We hypothesize that the incidence and duration of S/R should diminish significantly following the implementation of the program in both units. This naturalistic, prospective study covered archival data between April 2010 and July 2014. Pre-training data (April 2010–December 2011) were compared to data during training (January 2012–October 2012) and to post-training data (November 2012–July 2014) for both units. In the intensive care unit, we confirmed an increase of both mean daily number and duration of S/R by admissions in pre-training, followed by a decrease during the training and post-training. In the emergency unit, a decreasing trend is seen during the entire period thus suggesting that the decrease in S/R may be independent of the training. These findings suggest that Omega is a promising intervention program to use in an intensive care unit. However, a more global approach, including institutional changes in culture and attitude, can be important factors to develop to increase the positive outcomes.     

Suicidality and mood disorders in psychiatric emergency patients: Results from SBQ-R

Patients with mood disorders are at high risk of suicidality, and emergency departments (ED) are essential in the management of this risk. This study aims to (1) describe the suicidal thoughts and behaviours of patients with mood disorders who come to ED; (2) assess the psychometric properties of the Suicidal Behaviours Questionnaire-Revised (SBQ-R) in a psychiatric ED; and (3) determine the best predictors of suicidality for these patients. A total of 300 participants with mood disorders recruited for the Signature Bank of the Institut universitaire en santé mentale de Montréal (IUSMM) were retained. Suicidality was assessed using the SBQ-R. Other clinical and demographic details were recorded. Bivariate analyses, correlations and multivariate regression analyses were conducted. SBQ-R's internal consistency, construct and convergent validities were also tested. In the Patient Health Questionnaire-9 (PHQ-9), 53.3% of the sample stated they had suicidal or self-harm thoughts in the last 2 weeks. The mean score obtained at the SBQ-R was 8.3. Multivariate analysis found that SBQ-R scores were associated with depressive symptoms and substance use, especially alcohol, accounting for 44.3% of the model variance. Cronbach's alpha was 0.81 [0.78, 0.84] and factor loadings for items 1–4 were 0.68, 0.88, 0.54, and 0.85, respectively. The confirmatory factor analysis indicated that the model fit the data well. The SBQ-R is a brief and valid instrument that can easily be used in busy emergency departments to assess suicide risk. Depressive symptoms and alcohol use shall also be assessed, as they are determinants of increased risk of suicidality.