Acquistion and retention of categorized material in normal aging and senile dementia

The “shopping list task” is a new verbal learning task with a high degree of face validity for elderly subjects. Learning and delayed recall performance were examined for three groups of subjects: young normals (n=63, median age=21), elderly normals (n=44, median age=69) and mild to moderately impaired senile dementia patients (n=60, median age=70). The young normal subjects performed best of the three groups in both initial learning and delayed recall measures. The elderly normals showed significant decrements in learning and recalling the list items (p<.01). The impaired elderly showed much greater performance decrements in both learning and recall. None of the subjects showed a deficit in delayed recognition. These results suggest that both storage and retrieval difficulties occur in normal aging and dementia. The recognition test results suggest that recall deficits evidenced by both elderly groups are in large part due to faulty retrieval mechanisms. Since the shopping list task discriminated well among the three groups, it has potential for memory assessment in clinical settings.     

Manipulation of liver regeneration with macrophages to influence the hepatic progenitor cell niche

Insufficient regeneration of the adult liver is believed to cause failure to recover from severe liver disease. An undifferentiated cell population with stem-cell-like qualities known as hepatic progenitor cells (HPCs) is hypothesised to have a central role in regeneration of the adult liver during massive or chronic liver disease. Stem cells in other organ systems are believed to reside in a specialised microenvironment or niche that supports their maintenance and function. The existence of a hepatic stem cell niche might provide a means of therapeutically manipulating endogenous HPCs in vivo as a regenerative therapy.To investigate the physiological potential of HPCs to regenerate the mammalian liver, we have established a novel model of hepatocellular injury and HPC activation using genetic manipulation of hepatocytes. After hepatocyte senescence and death in this model (AhCre Mdm2^flox), HPCs expand and bring about the complete regeneration of the liver parenchyma.We demonstrate that a stereotypical niche, consisting partly of macrophages, exists in both animal models and correlating human disease. Using cell tracking, we show active recruitment of extrahepatic macrophages into this niche during injury. In health, intravenous injection of macrophages results in macrophage engraftment to the liver niche, with subsequent HPC activation and changes to liver structure and function.Within the niche, macrophages use paracrine signalling to control both HPC proliferation and cell fate via TWEAK (tumour-necrosis-factor-like weak inducer of apoptosis) and the Wnt signalling pathway, respectively. After hepatocellular injury, macrophages ingest hepatocyte debris, and release Wnt which promotes HPC differentiation into hepatocytes. TWEAK is vital for HPC proliferation in the AhCre Mdm2^flox model of regeneration. Here, the absence of TWEAK signalling results in liver failure and mortality.This work has demonstrated for the first time the ability of a solid organ to fully regenerate in the adult mammal from progenitor cells, and additionally highlights mechanisms by which this process can be modulated by either small molecule or cell therapy.FundingUniversity of Edinburgh.     

Exploring nurses' perceptions of collecting and using HOBIC measures to guide clinical practice and improve care

Ontario's Health Outcomes for Better Information and Care (HOBIC) is designed to help organizations and nurses plan and evaluate care by comparing patient outcomes with historical data on similar cases. Yet, fewer than 15% of patients in a 2010 study were found to have complete admission and discharge data sets. This low utilization rate of HOBIC measures prompted the current qualitative study, in which nurses from three clinical settings in an academic teaching hospital were interviewed to gain their perceptions related to collecting and using HOBIC measures in practice. The objective was to identify factors that promote or impede the collection and use of HOBIC data in clinical practice to improve patient care and outcomes. Analysis of interview results produced four key themes related to (a) use of HOBIC measures to inform patient care, (b) collecting and documenting HOBIC measures, (c) HOBIC as an afterthought and "black hole" and (d) impediments to assessing and documenting HOBIC measures because of language barriers, patients' cognitive status and lack of time. Recommendations to improve uptake include developing, implementing and evaluating a communication and learning plan that promotes HOBIC's values and benefits, and determining how managers and administrators perceive utilization of HOBIC at the clinical unit and organizational levels.     

Muscle activation patterns during walking from transtibial amputees recorded within the residual limb-prosthetic interface

ABSTRACT: BACKGROUND: Powered lower limb prostheses could be more functional if they had access to feedforward control signals from the user's nervous system. Myoelectric signals are one potential control source. The purpose of this study was to determine if muscle activation signals could be recorded from residual lower limb muscles within the prosthetic socket-limb interface during walking. METHODS: We recorded surface electromyography from three lower leg muscles (tibilias anterior, gastrocnemius medial head, gastrocnemius lateral head) and four upper leg muscles (vastus lateralis, rectus femoris, biceps femoris, and gluteus medius) of 12 unilateral transtibial amputee subjects and 12 non-amputee subjects during treadmill walking at 0.7, 1.0, 1.3, and 1.6 m/s. Muscle signals were recorded from the amputated leg of amputee subjects and the right leg of control subjects. For amputee subjects, lower leg muscle signals were recorded from within the limb-socket interface and from muscles above the knee. We quantified differences in the muscle activation profile between amputee and control groups during treadmill walking using cross-correlation analyses. We also assessed the step-to-step intersubject variability of these profiles by calculating variance-to-signal ratios. RESULTS: We found that amputee subjects demonstrated reliable muscle recruitment signals from residual lower leg muscles recorded within the prosthetic socket during walking, which were locked to particular phases of the gait cycle. However, muscle activation profile variability was higher for amputee subjects than for control subjects. CONCLUSION: Robotic lower limb prostheses could use myoelectric signals recorded from surface electrodes within the socket-limb interface to derive feedforward commands from the amputee's nervous system.     

Infection with Burkholderia cepacia complex bacteria and pulmonary exacerbations of cystic fibrosis

BACKGROUND: Studies have shown that cystic fibrosis (CF) patients who are chronically infected with Burkholderia cepacia complex bacteria may potentially acquire new strains of B cepacia. Our objective was to determine whether pulmonary exacerbations of CF are associated with acquisition of new B cepacia strains or with B cepacia strain replacement. METHODS: Thirty-six patients from seven centers who were chronically infected with B cepacia complex bacteria were prospectively followed up over a 38-month period. Patients had sputum cultures performed every 3 months while clinically stable and at the time of a pulmonary exacerbation. Each B cepacia complex isolate was speciated by polymerase chain reaction amplification of the recA gene to determine species status and was genotyped by pulsed-field gel electrophoresis to determine strain type. RESULTS: Thirty-five of 36 patients (97%) had chronic infection with Burkholderia cenocepacia III-A during clinical stability. All 36 patients maintained the same species and strain of B cepacia complex at the time of exacerbation as was found during clinical stability. B cepacia complex isolates retrieved during exacerbations were significantly less susceptible to ciprofloxacin, chloramphenicol, piperacillin, meropenem, and tobramycin compared to isolates retrieved from the same patients during clinical stability. CONCLUSION: Adult CF patients infected with B cenocepacia maintain the same strain of B cenocepacia during exacerbations; pulmonary exacerbations are not caused by acquisition of a new B cepacia species or strain. B cepacia isolates retrieved during exacerbations may be more resistant to antibiotics.     

The influence of disclosure of HIV diagnosis on time to disease progression in a cohort of Romanian children and teens

The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that in 2004, there were 39.4 million people living with HIV/AIDS worldwide (UNAIDS/WHO Report on the global HIV/AIDS epidemic, 2004). Children less than 15 years of age comprise 2.2 million of these individuals. As more children globally gain access to highly active antiretroviral therapy (HAART), more children are growing to the age when disclosure of their HIV status is inevitable. This information may affect a child's disease trajectory, and in the context of HAART, may have wide-ranging impact in the management of paediatric HIV infection. This study is an investigation of the effect of disclosure of a child's own HIV infection status on death and CD4 decline in a cohort of 325 HIV-infected Romanian children receiving highly active antiretroviral therapy (HAART). A retrospective database analysis was conducted. Data from a nearly three-year period were examined. Children who were aware of their HIV diagnosis were compared with those who were not aware. We found significant associations between not knowing the HIV diagnosis and death, and not knowing the HIV diagnosis and disease progression defined as either death or CD4 decline. Our results imply that in the context of HAART, knowledge of one's own HIV infection status is associated with delayed HIV disease progression.     

Sequential infection of tsetse flies with Trypanosoma congolense and Trypanosoma brucei.

The question whether tsetse flies can be experimentally infected with more than one trypanosome species or strain by sequential feeding was investigated using DNA probe technology to identify directly the small numbers of trypanosomes in the fly gut. Bloodstream form trypanosomes of Trypanosoma congolense or T. brucei ssp. were used for initial infection, followed by sequential feeds using either T. congolense or T. brucei ssp. Midgut trypanosome populations were subsequently analysed by hybridising dot blots with species-specific DNA probes. Two different T. brucei stocks were also fed in succession and the midgut trypanosome populations analysed by molecular karyotype. Contrary to expectations from previous reports, it was comparatively easy to superinfect flies with a second trypanosome species or stock, although the presence of trypanosomes already in the gut did not aid establishment of those incoming. Thus, to develop a mixed infection, a prerequisite for trypanosome mating, flies do not necessarily have to pick up both parental trypanosomes on their first feed.     

Inhibition of calcineurin phosphatase activity in adult bone marrow transplant patients treated with cyclosporine A

In vitro studies have demonstrated that cyclosporine A (CsA) acts by inhibiting the phosphatase activity of calcineurin, an important mediator of T-cell activation. The relationship of CsA administration in vivo, calcineurin activity, and graft-versus-host disease (GVHD) has yet to be studied. The calcineurin activities of mononuclear cells isolated from 62 bone marrow transplant recipients and 12 normal volunteers were determined and analyzed with respect to administration of CsA, presence or absence of CsA in plasma, and presence or absence of GVHD. Of 62 patients, 33 were taking CsA and 29 were not. Early posttransplant (< 100 days), the calcineurin activity of patients on CsA was significantly lower than that of patients not on CsA (P = .0004) and than that of normal volunteers (P < .0001). Similarly, late posttransplant (> 100 days), the calcineurin activity of patients taking CsA was inhibited compared with normal volunteers (P < .05). The calcineurin activity of patients with acute GVHD who were taking CsA was lower than that of patients on CsA without acute GVHD matched for time posttransplant (P = .02). Calcineurin activity in patients on CsA with chronic GVHD was similar to those without chronic GVHD on drug. In conclusion, calcineurin activity is significantly suppressed by in vivo administration of CsA. The lower calcineurin activity of patients on CsA with acute GVHD suggests that CsA-resistant GVHD is not the result of inadequate suppression of calcineurin activity. These data suggest that if inhibition of calcineurin is the only physiologic target of CsA administration, simply increasing doses of CsA or treatment with other inhibitors of calcineurin, such as FK506, would not be expected to ameliorate GVHD.