Heart Failure Impairs Bone Marrow Hematopoietic Stem Cell Function and Responses to Injury.

Background Heart failure (HF) is a clinical syndrome associated with a progressive decline in myocardial function and low-grade systemic inflammation. Chronic inflammation can have lasting effects on the bone marrow (BM) stem cell pool by impacting cell renewal and lineage differentiation. However, how HF affects BM stem/progenitor cells remains largely unexplored. Methods and Results EGFP+ (Enchanced green fluorescent protein) mice were subjected to coronary artery ligation, and BM was collected 8 weeks after myocardial infarction. Transplantation of EGFP+ BM into wild-type mice revealed reduced reconstitution potential of BM from mice subjected to myocardial infarction versus BM from sham mice. To study the effects HF has on human BM function, 71 patients, HF (n=20) and controls (n=51), who were scheduled for elective cardiac surgery were consented and enrolled in this study. Patients with HF exhibited more circulating blood myeloid cells, and analysis of patient BM revealed significant differences in cell composition and colony formation potential. Human CD34+ cell reconstitution potential was also assessed using the NOD-SCID-IL2rγnull mouse xenotransplant model. NOD-SCID-IL2rγnull mice reconstituted with BM from patients with HF had significantly fewer engrafted human CD34+ cells as well as reduced lymphoid cell production. Analysis of tissue repair responses using permanent left anteriordescending coronary artery ligation demonstrated reduced survival of HF-BM reconstituted mice as well as significant differences in human (donor) and mouse (host) cellular responses after MI. Conclusions HF alters the BM composition, adversely affects cell reconstitution potential, and alters cellular responses to injury. Further studies are needed to determine whether restoring BM function can impact disease progression or improve cellular responses to injury.

Intravenous lidocaine to prevent postoperative airway complications in adults: a systematic review and meta-analysis.

BACKGROUND: In surgical patients undergoing general anaesthesia, coughing at the time of extubation is common and can result in potentially dangerous complications. We performed a systematic review and meta-analysis to assess the efficacy and safety of i.v. lidocaine administration during the perioperative period to prevent cough and other airway complications. METHODS: We searched Medical Literature Analysis and Retrieval System, Excerpta Medica database, and Cochrane Central Register of Controlled Trials for RCTs comparing the perioperative use of i.v. lidocaine with a control group in adult patients undergoing surgery under general anaesthesia. The RCTs were assessed using risk-of-bias assessment, and the quality of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RESULTS: In 16 trials (n=1516), the administration of i.v. lidocaine compared with placebo or no treatment led to large reductions in post-extubation cough (risk ratio [RR]: 0.64; 95% confidence interval [CI]: 0.48-0.86) and in postoperative sore throat at 1 h (RR: 0.46; 95% CI: 0.32-0.67). There was no difference in incidence of laryngospasm (risk difference [RD]: 0.02; 95% CI: -0.07 to 0.03) or incidence of adverse events related to the use of lidocaine. CONCLUSIONS: The use of i.v. lidocaine perioperatively decreased airway complications, including coughing and sore throat. There was no associated increased risk of harm.

Preventing cancer: a community-based program for youths in public housing.

PURPOSE: This article describes a feasibility study of a program that mentors boys aged 14-18 living in inner city public housing, engages them in a basketball league, and provides educational sessions on life skills and ways to resolve conflicts without violence. Such programs have the potential to engage adolescent males living in public housing in activities that reduce cancer-related behaviors and increase protective behaviors. METHODS: We conducted a feasibility evaluation of the program, which included a survey of participants, interviews with coaches, and observations of games and practices. RESULTS: Lifetime and previous-30-day substance use was common among participants, and many were exposed to and had experienced various forms of violence. Keeping youths active helps prevent their joining gangs and using drugs. CONCLUSIONS: Youths from disadvantaged backgrounds are at a high risk for cancer because they are at greater risk for obesity and other adverse health-related conditions than are more affluent youths. Implementing and sustaining community programs for youths in public housing can reduce the effects of exposure to factors that put them at risk for cancer during adulthood: chronic poverty, lack of safe areas for recreation, easy access to alcohol and drugs, and exposure to violence. In addition, workshops to prevent substance use and violence and to teach leadership, sportsmanship, conflict resolution, and healthy youth development are needed for youths, coaches, and parents or guardians.

Step training reinforces specific spinal locomotor circuitry in adult spinal rats.

Locomotor training improves function after a spinal cord injury both in experimental and clinical settings. The activity-dependent mechanisms underlying such improvement, however, are sparsely understood. Adult rats received a complete spinal cord transection (T9), and epidural stimulation (ES) electrodes were secured to the dura matter at L2. EMG electrodes were implanted bilaterally in selected muscles. Using a servo-controlled body weight support system for bipedal stepping, five rats were trained 7 d/week for 6 weeks (30 min/d) under quipazine (0.3 mg/kg) and ES (L2; 40 Hz). Nontrained rats were handled as trained rats but did not receive quipazine or ES. At the end of the experiment, a subset of rats was used for c-fos immunohistochemistry. Three trained and three nontrained rats stepped for 1 h (ES; no quipazine) and were returned to their cages for 1 h before intracardiac perfusion. All rats could step with ES and quipazine administration. The trained rats had higher and longer steps, narrower base of support at stance, and lower variability in EMG parameters than nontrained rats, and these properties approached that of noninjured controls. After 1 h of stepping, the number of FOS+ neurons was significantly lower in trained than nontrained rats throughout the extent of the lumbosacral segments. These results suggest that training reinforces the efficacy of specific sensorimotor pathways, resulting in a more selective and stable network of neurons that controls locomotion.