Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism

Monocytes have a crucial role in both proinflammatory and anti-inflammatory phenomena occurring during sepsis. Monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2 and their cognate ligands. However, little is known about the roles of these cells and chemokines during the acute phase of inflammation in sepsis. Using intravital microscopy in a murine model of polymicrobial sepsis, we showed that inflammatory Ly6C^high monocytes infiltrated kidneys, exhibited altered motility, and adhered strongly to the renal vascular wall in a chemokine receptor CX3CR1-dependent manner. Adoptive transfer of Cx3cr1-proficient monocyte-enriched bone marrow cells into septic Cx3cr1-depleted mice prevented kidney damage and promoted mouse survival. Modulation of CX3CR1 activation in septic mice controlled monocyte adhesion, regulated proinflammatory and anti-inflammatory cytokine expression, and was associated with the extent of kidney lesions such that the number of lesions decreased when CX3CR1 activity increased. Consistent with these results, the pro-adhesive I249 CX3CR1 allele in humans was associated with a lower incidence of AKI in patients with sepsis. These data show that inflammatory monocytes have a protective effect during sepsis via a CX3CR1-dependent adhesion mechanism. This receptor might be a new therapeutic target for kidney injury during sepsis.     

Differential liver protein expression during schistosomiasis

The arrival of eggs in the liver during Schistosoma mansoni infection initiates a protective granulomatous response; however, as the infection progresses, this response results in chronic liver fibrosis. To better understand the impact of schistosomiasis on liver function, we used a proteomic approach to identify proteins whose expression was significantly altered in schistosome-infected mice 8 weeks postinfection. Identification of differentially expressed proteins by mass fingerprinting revealed that schistosome infection markedly reduced the abundance of proteins associated with several normal liver functions (i.e., citric acid cycle, fatty acid cycle, and urea cycle), while proteins associated with stress responses, acute phase reactants, and structural components were all significantly more abundant. The expression patterns of several immunity-related proteins (peroxiredoxin 1, arginase 1, and galectin 1) suggested that different protein forms are associated with schistosome infection. These findings indicate that acute schistosomiasis has a significant impact on specific liver functions and, moreover, that the alterations in specific protein isoforms and upregulation of unique proteins may be valuable as new markers of disease.     

Starting Off on the Best Foot: A Review of Message Framing and Message Tailoring,and Recommendations for the Comprehensive Messaging Strategy for Sustained Behavior Change

Health promotion programs represent a salient means through which physical activity promoters can cultivate positive health behavior change and maintenance. The messages communicated within these programs serve as an essential component as they are often used to convey valuable information, resources, or tools that facilitate health behavior initiation and sustained engagement. Identifying the most effective way to communicate health promotion information is, therefore, of considerable importance to ensuring that people not only attend to these messages, but also connect with and internalize the information conveyed within them. This paper was written to (1) summarize and evaluate the most prominent reviewed research approaches of message framing and tailoring to message design; and (2) offer a comprehensive messaging strategy to promote sustained health behavior change. A review of the literature demonstrated that a messaging strategy that has consistently led to healthy behavior change has yet to be identified. Furthermore, scholars have articulated that a multi-theoretical approach that places emphasis on facilitating motivation and healthy behavior change needs to be employed. Thus, this paper proposes and provides recommendations for employing the Comprehensive Messaging Strategy for Sustained Behavior Change (CMSSBC), which advocates tailoring messages to peoples’ stage of change and framing them to focus on self-determined motives and intrinsic goals.     

Correction of pelvic obliquity in neuromuscular spinal deformities using the “T construct”: results and complications in a prospective series of 60 patients

Background

We present the results of a prospective series of 60 patients treated for neuromuscular spinal deformities with an original spinopelvic construct using two sacral screws and two iliac screws. Clinical and radiological results obtained with this new surgical technique were studied and discussed according to the epidemiological data and relevant literature.

Methods

From January 2008 to June 2010, the clinical data of every patient who underwent spinopelvic fixation for treatment of a neuromuscular spinal deformity were recorded prospectively.

Results

Sixty patients were operated on during the study period. Spinal correction and fusion was performed by posterior approach. In six patients with a residual spinopelvic imbalance more than 15° on lateral preoperative bending films, an anterior release of the thoracolumbar junction was performed on the same day, before posterior correction. Preoperative pelvic obliquity (PO) ranged from 4° to 44° (mean 21.6°). Postoperative pelvic obliquity ranged from 0° to 14 (mean 4.6°). No significant loss of correction was noted at the last follow-up. One patient died 3 months after the initial procedure due to respiratory compromise. 11 patients had early postoperative infections of the posterior approach.

Conclusions

Despite a high rate of infectious complications, optimal correction of pelvic obliquity requires extension of spinal instrumentation to the pelvis. Spinopelvic fixation remains a difficult challenge in neurological patients with hypotrophy. We think that pelvic fixation with the “T construct” did provide effective and improved spinal stabilization in these patients, while reducing the need for a postoperative cast or brace. As a result, patients had a favourable postoperative course with early mobilization and return to a comfortable sitting position.     

Respiratory effects of buprenorphine/naloxone alone and in combination with diazepam in naive and tolerant rats

Respiratory depression has been attributed to buprenorphine (BUP) misuse or combination with benzodiazepines. BUP/naloxone (NLX) has been marketed as maintenance treatment, aiming at preventing opiate addicts from self-injecting crushed pills. However, to date, BUP/NLX benefits in comparison to BUP alone remain debated. We investigated the plethysmography effects of BUP/NLX in comparison to BUP/solvent administered by intravenous route in naive and BUP-tolerant Sprague-Dawley rats, and in combination with diazepam (DZP) or its solvent. In naive rats, BUP/NLX in comparison to BUP significantly increased respiratory frequency (f, P < 0.05) without altering minute volume (V_E). In combination to DZP, BUP/NLX significantly increased expiratory time (P < 0.01) and decreased f (P < 0.01), tidal volume (V_T, P < 0.001), and V_E (P < 0.001) while BUP only decreased V_T (P < 0.5). In BUP-tolerant rats, no significant differences in respiratory effects were observed between BUP/NLX and BUP. In contrast, in combination to DZP, BUP/NLX did not significantly alter the plethysmography parameters, while BUP increased inspiratory time (P < 0.001) and decreased f (P < 0.01) and V_E (P < 0.001). In conclusion, differences in respiratory effects between BUP/NLX and BUP are only significant in combination with DZP, with increased depression in naive rats but reduced depression in BUP-tolerant rats. However, BUP/NLX benefits in humans remain to be determined.     

The risk of being ‘too honest’: drug use,stigma and pregnancy

In this article, I examine the ways in which risk is constructed and managed by those involved in the pregnancy and childbirth of women who use drugs, including the women themselves. I discuss how constructions of risk influence maternal care outcomes and the understanding of choice, often in the form of stigmatisation. In this article, I draw on data from a qualitative research study that I conducted in 2011 in a western Canada city in which I interviewed 13 pregnant and parenting women who had used drugs during their pregnancy. In this article, I show how the everyday risk construction of pregnancy, labour and delivery is compounded significantly by drug use and the stigmatisation associated with this perceived risk-taking behaviour. The participants in the study often internalised this understanding of risk and this manifested itself in delays in accessing maternal health and social care services. The women in the study had different understandings of risk and these were structured by the women’s own understanding of general risk factors during their pregnancy, as well as their experiences of the constructions of risk and risk management by health and social care professionals. While structural life chances can constrain women’s feelings of self-efficacy, services that promote clients’ ability to make choices can facilitate reduced stigmatisation and facilitate the development of more compassionate and autonomous approaches to risk management.