Nonmyeloablative allogeneic bone marrow transplantation for orbital granulocytic sarcoma associated with t(8;21)(q22;q22) in acute myeloid leukemia

We report a nonmyeloablative allogeneic bone marrow transplant (allo-BMT) from an HLA-matched unrelated donor in a case of acute myeloid leukemia (AML), M2 with t(8;21)(q22;q22) and the presence of orbital granulocytic sarcoma (GS), who had residual tumor after conventional chemotherapy. The course of BMT was well tolerated, with no major procedure-related toxicity. The residual orbital GS regressed completely 4 months after BMT. She is currently 19 months post BMT, disease-free. To our knowledge, this is the first reported pediatric patient with AML, GS and t(8;21)(q22;q22) who received a nonmyeloablative allo-BMT.     

Basal sympathetic predominance in periodic limb movements in sleep with obstructive sleep apnea

Because the impact of periodic limb movements in sleep (PLMS) is controversial, no consensus has been reached on the therapeutic strategy for PLMS in obstructive sleep apnea (OSA). To verify the hypothesis that PLMS is related to a negative impact on the cardiovascular system in OSA patients, this study investigated the basal autonomic regulation by heart rate variability (HRV) analysis. Sixty patients with mild‐to‐moderate OSA who underwent polysomnography (PSG) and completed sleep questionnaires were analysed retrospectively and divided into the PLMS group (n = 30) and the non‐PLMS group (n = 30). Epochs without any sleep events or continuous effects were evaluated using HRV analysis. No significant difference was observed in the demographic data, PSG parameters or sleep questionnaires between the PLMS and non‐PLMS groups, except for age. Patients in the PLMS group had significantly lower normalized high frequency (n‐HF), high frequency (HF), square root of the mean of the sum of the squares of difference between adjacent NN intervals (RMSSD) and standard deviation of all normal to normal intervals index (SDNN‐I), but had a higher normalized low frequency (n‐LF) and LF/HF ratio. There was no significant difference in the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the Short‐Form 36 and the Hospital Anxiety and Depression Scale between the two groups. After adjustment for confounding variables, PLMS remained an independent predictor of n‐LF (β = 0.0901, P = 0.0081), LF/HF ratio (β = 0.5351, P = 0.0361), RMSSD (β = ?20.1620, P = 0.0455) and n‐HF (β = ?0.0886, P = 0.0134). In conclusion, PLMS is related independently to basal sympathetic predominance and has a potentially negative impact on the cardiovascular system of OSA patients.     

Inducibility of atrial fibrillation during atrioventricular pacing with varying intervals: role of atrial electrophysiology and the autonomic nervous system

INTRODUCTION: Patients receiving VVI pacemakers have a higher incidence of paroxysmal atrial fibrillation (AF) than those receiving DDD pacemakers. However, the mechanism behind the difference is not clear. The purpose of this study was to investigate whether atrial electrophysiology and the autonomic nervous system play a role in the occurrence of AF during AV pacing. METHODS AND RESULTS: The study population consisted of 28 patients who had (group I, n = 15) or did not have (group II, n = 13) AF induced by a single extrastimulus during pacing with different AV intervals. Atrial pressure, atrial size, atrial effective refractory periods, and atrial dispersion were evaluated during pacing with different AV intervals. Twenty-four-hour heart rate variability and baroreflex sensitivity also were examined. Atrial pressure, atrial size, effective refractory periods in the right posterolateral atrium and distal coronary sinus, and atrial dispersion increased as the AV interval shortened from 160 to 0 msec. During AV pacing, group I patients had greater minimal (52+/-17 vs 25+/-7 msec; P < 0.005) and maximal (76+/-16 vs 36+/-9 msec; P < 0.005) atrial dispersion than group II patients. The differences in atrial size and atrial dispersion among different AV intervals were greater in patients with AF than in those without AF. Baroreflex sensitivity (6.6+/-1.7 vs 3.9+/-1.0; P < 0.00005), but not heart rate variability, was higher in patients with AF than in those without AF. CONCLUSION: Abnormal atrial electrophysiology and higher vagal reflex activity can play important roles in the genesis of AF in patients receiving pacemakers.     

Molecular basis of altered red blood cell membrane properties in Southeast Asian ovalocytosis: role of the mutant band 3 protein in band 3 oligomerization and retention by the membrane skeleton

Southeast Asian ovalocytosis (SAO) is an asymptomatic trait characterized by rigid, poorly deformable red cells that resist invasion by several strains of malaria parasites. The underlying molecular genetic defect involves simple heterozygous state for a mutant band 3 protein, which contains a deletion of amino acids 400 through 408, linked with a Lys 56-to-Glu substitution (band 3-Memphis polymorphism). To elucidate the contribution of the mutant SAO band 3 protein to increased SAO red blood cell (RBC) rigidity, we examined the participation of the mutant SAO band 3 protein in increased band 3 attachment to the skeleton and band 3 oligomerization. We found first that SAO RBC skeletons retained more band 3 than normal cells and that this increased retention preferentially involved the mutant SAO band 3 protein. Second, SAO RBCs contained a higher percentage of band 3 oligomer-ankyrin complexes than normal cells, and these oligomers were preferentially enriched by the mutant SAO protein. At the ultrastructural level, the increased oligomer formation of SAO RBCs was reflected by stacking of band 3-containing intramembrane particles (IMP) into longitudinal strands. The IMP stacking was not reversed by treating SAO RBCs in alkaline pH (pH 11), which is known to weaken ankyrin-band 3 interactions, or by removing the cytoplasmic domain of band 3 from SAO membranes with trypsin. Finally, we found that band 3 protein in intact SAO RBCs exhibited a markedly decreased rotational mobility, presumably reflecting the increased oligomerization and the membrane skeletal association of the SAO band 3 protein. We propose that the mutant SAO band 3 has an increased propensity to form oligomers, which appear as longitudinal strands of IMP and exhibit increased association with membrane skeleton. This band 3 oligomerization underlies the increase in membrane rigidity by precluding membrane skeletal extension, which is necessary for membrane deformation.     

Educating and Training a Workforce for Nutrition in a Post-2015 World

Nearly all countries in the world today are burdened with malnutrition, manifesting as undernutrition, micronutrient deficiencies, and/or overweight and obesity. Despite some progress, efforts to alleviate malnutrition are hampered by a shortage in number, skills, and geographic coverage, of a workforce for nutrition. Here, we report the findings of the Castel Gandolfo workshop, a convening of experts from diverse fields in March 2014 to consider how to develop the capacity of a global cadre of nutrition professionals for the post-2015 development era. Workshop participants identified several requirements for developing a workforce for nutrition, including an ability to work as part of a multisectoral team; communication, advocacy, and leadership skills to engage decision makers; and a set of technical skills to address future challenges for nutrition. Other opportunities were highlighted that could immediately contribute to capacity development, including the creation of a consortium to link global North and South universities, online training modules for middle managers, and practical, hands-on experiences for frontline nutrition workers. Institutional and organizational support is needed to enable workshop recommendations on education and training to be effectively implemented and sustained. The findings from the Castel Gandolfo workshop can contribute to the delivery of successful nutrition-relevant actions in the face of mounting external pressures and informing and attaining the forthcoming Sustainable Development Goals.