Cholinergic leukocytes in sepsis and at the neuroimmune junction in the spleen.

The spleen is a key participant in the pathophysiology of sepsis and inflammatory disease. Many splenocytes exhibit a cholinergic phenotype, but our knowledge regarding their cholinergic biology and how they are affected by sepsis is incomplete. We evaluated effects of acute sepsis on the spleen using the cecal ligation and puncture (CLP) model in C57BL/6 and ChATBAC-eGFP mice. Quantification of cholinergic gene expression showed that choline acetyltransferase and vesicular acetylcholine transporter (VAChT) are present and that VAChT is upregulated in sepsis, suggesting increased capacity for release of acetylcholine (ACh). High affinity choline transporter is not expressed but organic acid transporters are, providing additional mechanisms for release. Flow cytometry studies identified subpopulations of cholinergic T and B cells as well as monocytes/macrophages. Neither abundance nor GFP intensity of cholinergic T cells changed in sepsis, suggesting that ACh synthetic capacity was not altered. Spleens have low acetylcholinesterase activity, and the enzyme is localized primarily in red pulp, characteristics expected to favor cholinergic signaling. For cellular studies, ACh was quantified by mass spectroscopy using d4-ACh internal standard. Isolated splenocytes from male mice contain more ACh than females, suggesting the potential for gender-dependent differences in cholinergic immune function. Isolated splenocytes exhibit basal ACh release, which can be increased by isoproterenol (4 and 24 h) or by T cell activation with antibodies to CD3 and CD28 (24 h). Collectively, these data support the concept that sepsis enhances cholinergic function in the spleen and that release of ACh can be triggered by stimuli via different mechanisms.

Effects of once weekly dual-task training in older adults: a pilot randomized controlled trial.

AIM: To compare single-task and dual-task training on obstacle avoidance, gait speed and balance in healthy community-dwelling older adults. METHODS: A total of 17 older adults (65-83 years) participated in a group circuit class, once weekly for 45 min for 4 weeks. The dual-task group carried out cognitive activities simultaneously with gait and balance exercises. The single-task training group carried out identical gait and balance activities without cognitive tasks. We assessed time to complete a 6-m obstacle course under single-task and three different dual-task conditions (spontaneous speech, alphabet recitation and coin transfer), 25-ft gait speed, Timed Up and Go, and the Activities-specific Balance Confidence Scale. RESULTS: Both groups showed significant improvement in gait speed and Timed Up and Go. In addition, the proportion of participants who achieved gait speed >1.0 m/s increased in both groups. There were no within- or between-subjects differences in obstacle course performance under single or dual-task conditions after the intervention. CONCLUSION: Once weekly group circuit training focusing on balance, gait and agility, with or without simultaneous cognitive tasks, resulted in significantly improved walking speed among older adults. Group-format dual-task training once per week did not improve walking time or dual-task cost on an obstacle negotiation task.

Bone marrow transplantation for beta-thalassaemia major: the UK experience in two paediatric centres.

Stem cell transplantation (SCT) remains the only cure for thalassaemia major. Recent advances in medical treatment make it even more important that accurate information is available regarding outcome of SCT in relevant patient populations in order to guide informed decisions regarding the most appropriate treatment for individual thalassaemia patients. We report the results of 55 consecutive first related allogeneic bone marrow transplants (BMT) for children with beta-thalassaemia major performed in two UK paediatric centres over 10 years. Between February 1991 and February 2001, 55 children underwent 57 allogeneic BMT. The median age at BMT was 6.4 years and the majority of patients (73%) originated from the Indian subcontinent. Using the Pesaro risk classification, 17 patients were class 1, 27 were class 2 and 11 were class 3. Actuarial overall survival and thalassaemia-free survival at 8 years were 94.5% (95% CI 85.1-98.1) and 81.8% (95% CI 69.7-89.8) respectively. Despite the majority of patients being in class 2 or 3, transplant-related mortality was low (5.4%). The principal complication was graft rejection accompanied by autologous reconstitution that occurred in 13.2% of transplants. Following modification of the conditioning regimen in 1993, the rejection rate fell to 4.6% and remained low. Acute graft-versus-host disease (GVHD) of grade II-IV occurred in 31% and chronic GVHD in 14.5%. These data compare favourably with survival with medical treatment for thalassaemia major and suggest that allogeneic BMT remains an important treatment option for children with beta-thalassaemia major, particularly when compliance with iron chelation is poor.