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.     

Covid-19 in liver transplant recipients: the French SOT COVID registry

BackgroundNotwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in organ transplant recipients remains limited. The aim of this registry-based observational study was to report the characteristics and clinical outcomes of liver transplant (LT) recipients included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19.MethodsCOVID-19 was diagnosed in patients who had a positive PCR assay for SARS-CoV-2 or in presence of typical lung lesions on imaging or specific SARS-CoV-2 antibodies. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded.ResultsOf the 104 patients, 67 were admitted to hospital and 37 were managed at home (including all 13 children). Hospitalized patients had a median age of 65.2 years (IQR: 58.1 ? 73.2 years) and two thirds were men. Most common comorbidities included overweight (67.3%), hypertension (61.2%), diabetes (50.7%), cardiovascular disease (20.9%) and respiratory disease (16.4%). SARS-CoV-2 infection was identified after a median of 92.8 months (IQR: 40.1 ? 194.7 months) from LT. During hospitalization, antimetabolites, mTOR inhibitor, and CNIs were withdrawn in 41.9%, 30.0% and 12.5% of patients, respectively. The composite endpoint of severe Covid-19 within 30 days after diagnosis was reached by 33.0% of the adult patients. The 30-day mortality rate was 20.0%, and 28.1% for hospitalized patients. Multivariate analysis identified that age was independently associated with mortality.ConclusionIn our large nationwide study, Covid-19 in LT recipients was associated with a high mortality rate.     

Challenges in Statewide Implementation of a Prehospital Evidence-Based Guideline: An Assessment of Barriers and Enablers in Five States

Background: Individual states, regions, and local emergency medical service (EMS) agencies are responsible for the development and implementation of prehospital patient care protocols. Many states lack model prehospital guidelines for managing common conditions. Recently developed national evidence-based guidelines (EBGs) may address this gap. Barriers to statewide dissemination and implementation of model guidelines have not been studied. The objective of this study was to examine barriers and enablers to dissemination and implementation of an evidence-based guideline for traumatic pain management across 5 states. Methods: This study used mixed methods to evaluate the statewide dissemination and implementation of a prehospital EBG. The guideline provided pain assessment tools, recommended opiate medication dosing, and indications and contraindications for analgesia. Participating states were provided an implementation toolkit, standardized training materials, and a state-specific implementation plan. Outcomes were assessed via an electronic self-assessment tool in which states reported barriers and enablers to dissemination and implementation and information about changes in pain management practices in their states after implementation of the EBG. Results: Of the 5 participating states, 3 reported dissemination of the guideline, one through a state model guideline process and 2 through regional EMS systems. Two states did not disseminate or implement the guideline. Of these, one state chose to utilize a locally developed guideline, and the other state did not perform guideline dissemination at the state level. Barriers to state implementation were the lack of authority at the state level to mandate protocols, technical challenges with learning management systems, and inability to track and monitor training and implementation at the agency level. Enablers included having a state/regional EMS office champion and the availability of an implementation toolkit. No participating states demonstrated an increase in opioid delivery to patients during the study period. Conclusion: Statewide dissemination and implementation of an EBG is complex with many challenges. Future efforts should consider the advantages of having statewide model or mandatory guidelines and the value of local champions and be aware of the challenges of a statewide learning management system and of tracking the success of implementation efforts.     

Skeletal myoblast transplantation through a catheter-based coronary sinus approach: an effective means of improving function of infarcted myocardium.

AIMS: This study was designed to assess the functional effects of a transvenous coronary sinus technique of skeletal myoblast delivery in infarcted myocardium. METHODS AND RESULTS: An anterior myocardial infarction was created percutaneously in 14 sheep. Simultaneously, a muscle biopsy was harvested and expanded. Two weeks later, sheep were instrumented percutaneously with a dedicated catheter incorporating an extendable needle for puncture of the venous wall and, under endovascular ultrasound guidance, a microcatheter was advanced through the needle into the target scar for cell delivery. Following the baseline echocardiographic assessment of left ventricular (LV) function, sheep were randomly allocated to receive four-staged in-scar injections of either autologous cells (n=7) or culture medium (n=7). Two months later, LV function was reassessed blindly and hearts were explanted for subsequent histological and immunohistochemical analysis. There were no acute procedural complications. Baseline LV ejection fraction (EF) was significantly lower in transplanted sheep than in controls [38% (35-48) vs. 51% (38-55), respectively, P=0.03; median (range)]. Two months later, LVEF was significantly higher in the transplanted group than in controls [50% (47-56) vs. 39% (36-47), respectively, P=0.002]. Clusters of myoblasts were identified by histology and immunohistochemistry in three of the seven transplanted sheep. CONCLUSION: These data suggest the functional efficacy of the transvenous coronary sinus technique as a less invasive means of cell delivery to infarcted myocardium.