Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death

Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC₅₀ (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolate (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC₅₀ (concentration at which 50% of maximal cell death is inhibited) of 0.6 μM and 0.4 μM, respectively. In contrast, MTHF (up to 10 μM) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron-neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS.     

Improving nurse care coordination with technology

Technology offers potential solutions to the pending crisis of healthcare for older adults, while healthcare workers are in short supply. Technology can enable remote monitoring of individuals and early detection of potential problems, so that early interventions can help older adults remain as healthy and independent as possible. Research is under way with passive monitoring technology in senior housing that is finding patterns in the data that can enhance nurse care coordination through early illness detection. With early detection, interventions can be more effective and reduce hospitalization and other healthcare expenses. Case studies are presented, and implications are discussed.     

Evaluating multivariate risk scores for clinical decision making

The medical literature abounds with risk scores that can help clinicians predict the probability of disease. Risk scores are popular and attractive because they synthesize the effects of several different risk factors for disease in a way that is otherwise too complex for the human mind alone to analyze. However, to optimize clinical decision making, users of risk scores need to consider the factors and methods used to create the score and to recognize the potential limitations of risk scores. Clinicians should consider the patient populations in which the risk score has been developed and validated, the risk factors included in the score, how computing the score might fit into the flow of daily practice, and how risk scores can help estimate pretest probability. An awareness of the uses and potential limitations of using risk assessment tools will aid the clinician in daily clinical decision making. These tools may grow in importance and use with increasing utilization of electronic health records.     

Caffeine consumption during development alters spine density and recovery from repetitive mild traumatic brain injury in young adult rats

Caffeine is the most commonly used psychostimulant throughout the world, with its consumption being especially prevalent among adolescents and young adults, as over 75% of this group consumes caffeine daily. Similarly, the adolescent and young adult age group exhibit the highest incidence of traumatic brain injury (TBI). Given that both caffeine consumption and mild TBI (mTBI) are more prevalent among the late adolescent/young adult age group and that changes in dendritic spine morphology during this developmental period are poorly understood, this study sought to examine the effects of caffeine consumption during late adolescence/early adulthood on recovery from repetitive mTBI (RmTBI). The study specifically focused on changes to neuronal dendritic morphology as synaptic changes likely underlie long-term behavioral outcomes. The results demonstrate that during young adulthood caffeine consumption differentially affects the RmTBI outcomes of males and females, where the effects of caffeine and RmTBI were often additive in males while being equally detrimental, but rarely additive, in females. In general, caffeine and RmTBI induced the greatest impairments in males on cognitive and motor tasks whereas in females the most significant detriments were on pain-related tasks. Both caffeine and RmTBI increased spine density in the Cg3 (medial prefrontal cortex [mPFC]), AID (orbitofrontal cortex [OFC]), and nucleus accumbens (NAc), which is proposed to reflect an impairment in the normal pruning processes. Overall, despite caffeine's neuroprotective abilities among other age groups, this study offers concerning results regarding the detrimental effects of caffeine and RmTBI, in isolation, and especially in combination, in this susceptible population.     

Intriguing Case: Primitive Pelvic Sarcoma Resembling Clear Cell Sarcoma of Kidney

Clear cell sarcoma of kidney (CCSK) is an aggressive childhood renal tumor of unknown histogenesis that has not been reported to occur outside the kidney. The article describes an extrarenal neoplasm arising in the pelvic soft tissues of a 13-year-old boy that was composed predominantly of uniform mesenchymal cells with optically clear cytoplasm supported by an arborizing network of small blood vessels, which was indistinguishable in appearance from CCSK. The electron microscopic findings, although nonspecific, were essentially identical to those of CCSK, with tumor cells displaying fine chromatin, electron-lucent cytoplasm, and intercellular collagen but no evidence of tissue-specific differentiation. Immunocytochemical studies showed positivity for vimentin but negative results for desmin, myoglobin, cytokeratin, epithelial membrane antigen, S-100 protein, neuron-specific enolase and factor VIII-related antigen. Tumor cells were also nonreactive with Ulex lectin. This unusual pelvic tumor and CCSK may both derive from primitive mesenchymal cells and may represent phenotypic but not necessarily histogenetic analogs.     

Manipulation of tissue fatty acid profile by intravenous lipids in dogs

This study was undertaken to determine the effects on the fatty acid (FA) composition of various dog tissues of 4 different lipid emulsions (a 100% long-chain triacylglycerol (LCT) derived from soya bean oil emulsion, a mixed 50% medium-chain triacylglycerol (MCT)/50% LCT emulsion as well as both these emulsions supplemented with 10% fish oil (FO) triacylglycerols), when daily infused over 15 days as a substantial component of total parenteral nutrition. Lipids represented 55% of the non-protein energy. Blood samples as well as biopsies from liver, muscle and adipose tissue were taken 15 days before, and again immediately after TPN. In addition, the spleen was also removed immediately after TPN. Tissue FA composition was analysed by gas liquid chromatography of each lipid component after separation by thin layer chromatography. No differences in either safety or tolerance were detected between the different TPN preparations. In particular, infusion over 2 weeks of fat emulsions containing 10% fish oil was tolerated as well as conventional LCT and MCT/LCT emulsions. Relative linoleate content of tissue triacylglycerol (TG) was markedly increased in animals that received the LCT emulsions (e.g. from 22.6 +/- 2.5% to 32.2 +/- 0.6% in the liver), this effect being markedly reduced with MCT/LCT preparations. n-3FA were slightly incorporated into liver TG (from 0.0 +/- 0.0% to 2.3 +/- 0.7% and 1.2 +/- 0.4% for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) respectively, with LCT + FO), but remained undetectable in extrahepatic tissue TG. Of interest, medium chain FA were found in tissue TG after infusion of the mixed MCT/LCT emulsions. As expected, changes of tissue phospholipid (PL) composition involved only long-chain FA. Infusion of soya bean oil emulsion was associated with an increased content of linoleate in liver PL (from 13.6 +/- 0.4% to 17.7 +/- 0.4%), but not in other tissues. MCT/LCT did not markedly affect PL/FA pattern in any tissue. Supplementation with fish oil was associated with an efficient incorporation of n-3FA into tissue PL, particularly in the liver (from 0.4 +/- 0.1% to 2.5 +/- 0.3% for EPA and from 3.9 +/- 0.8% to 9.1 +/- 0.4% for DHA, with the LCT + FO emulsion).