Brain stiffens post mortem.

Alterations in brain rheology are increasingly recognized as a diagnostic marker for various neurological conditions. Magnetic resonance elastography now allows us to assess brain rheology repeatably, reproducibly, and non-invasively in vivo. Recent elastography studies suggest that brain stiffness decreases one percent per year during normal aging, and is significantly reduced in Alzheimer's disease and multiple sclerosis. While existing studies successfully compare brain stiffnesses across different populations, they fail to provide insight into changes within the same brain. Here we characterize rheological alterations in one and the same brain under extreme metabolic changes: alive and dead. Strikingly, the storage and loss moduli of the cerebrum increased by 26% and 60% within only three minutes post mortem and continued to increase by 40% and 103% within 45 minutes. Immediate post mortem stiffening displayed pronounced regional variations; it was largest in the corpus callosum and smallest in the brainstem. We postulate that post mortem stiffening is a manifestation of alterations in polarization, oxidation, perfusion, and metabolism immediately after death. Our results suggest that the stiffness of our brain-unlike any other organ-is a dynamic property that is highly sensitive to the metabolic environment. Our findings emphasize the importance of characterizing brain tissue in vivo and question the relevance of ex vivo brain tissue testing as a whole. Knowing the true stiffness of the living brain has important consequences in diagnosing neurological conditions, planning neurosurgical procedures, and modeling the brain's response to high impact loading.

Modeling molecular mechanisms in the axon.

Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena-both in isolation and in interaction-to explore emergent cellular-level features under physiological and pathological conditions.

Brain stiffness increases with myelin content.

UNLABELLED: Brain stiffness plays an important role in neuronal development and disease, but reported stiffness values vary significantly for different species, for different brains, and even for different regions within the same brain. Despite extensive research throughout the past decade, the mechanistic origin of these stiffness variations remains elusive. Here we show that brain tissue stiffness is correlated to the underlying tissue microstructure and directly proportional to the local myelin content. In 116 indentation tests of six freshly harvested bovine brains, we found that the cerebral stiffnesses of 1.33±0.63kPa in white matter and 0.68±0.20kPa in gray matter were significantly different (p<0.01). Strikingly, while the inter-specimen variation was rather moderate, the minimum and maximum cerebral white matter stiffnesses of 0.59±0.19 kPa and 2.36±0.64kPa in each brain varied by a factor of four on average. To provide a mechanistic interpretation for this variation, we performed a histological characterization of the tested brain regions. We stained the samples with hematoxylin and eosin and luxol fast blue and quantified the local myelin content using image analysis. Interestingly, we found that the cerebral white matter stiffness increased with increasing myelin content, from 0.72kPa at a myelin content of 64-2.45kPa at a myelin content of 89%, with a Pearson correlation coefficient of ρ=0.91 (p<0.01). This direct correlation could have significant neurological implications. During development, our results could help explain why immature, incompletely myelinated brains are softer than mature, myelinated brains and more vulnerable to mechanical insult as evident, for example, in shaken baby syndrome. During demyelinating disease, our findings suggest to use stiffness alterations as clinical markers for demyelination to quantify the onset of disease progression, for example, in multiple sclerosis. Taken together, our study indicates that myelin might play a more important function than previously thought: It not only insulates signal propagation and improves electrical function of single axons, it also provides structural support and mechanical stiffness to the brain as a whole. STATEMENT OF SIGNIFICANCE: Increasing evidence suggests that the mechanical environment of the brain plays an important role in neuronal development and disease. Reported stiffness values vary significantly, but the origin of these variations remains unknown. Here we show that stiffness of our brain is correlated to the underlying tissue microstructure and directly proportional to the local myelin content. Myelin has been discovered in 1854 as an insulating layer around nerve cells to improve electric signal propagation. Our study now shows that it also plays an important mechanical role: Using a combined mechanical characterization and histological characterization, we found that the white matter stiffness increases linearly with increasing myelin content, from 0.5kPa at a myelin content of 63-2.5kPa at 92%.

Cardiovascular health check in the elderly in one general practice: does it offer new information and lead to interventions?

BACKGROUND: Prevention of cardiovascular disease in the elderly is becoming increasingly important. GPs are in a unique position to initiate preventive interventions in this age group. However, it is not clear which strategy a GP should follow to identify patients at increased cardiovascular risk-case finding or screening. OBJECTIVE: We aimed to assess the value of a single cardiovascular health check compared with a normal care case finding and to investigate the diagnostic or therapeutic consequences of detecting new cardiovascular risk indicators. METHODS: In 1991, 1002 persons aged 60 years and over, enlisted in one general practice, were invited. Of the 805 subjects who responded (80%), the cardiovascular risk profile was determined by a research physician. The proportion of newly detected cardiovascular risk indicators was the main outcome measure. A risk indicator was considered newly detected when it was not mentioned in the GP's summary of the patient record, which had been checked by the patient for its completeness. The patient records of participants with newly detected hypertension, diabetes or hypercholesterolaemia were systematically reviewed to detect diagnostic and therapeutic interventions by the GP. RESULTS: In 25.1% of the participants, one or more cardiovascular risk indicators were found which were previously unknown to the GP, including 38 (4.7%) cases of hypertension, 82 (10%) cases of isolated systolic hypertension, 14 (1.7%) cases of diabetes mellitus and 63 (7.8%) cases of hypercholesterolaemia. On the basis of these findings, the GP initiated therapeutic interventions in almost all subjects with newly detected diabetes. However, reports of newly detected hypertension or high cholesterol levels were usually not followed by an intervention. CONCLUSION: A single cardiovascular health check in the elderly can detect a considerable number of risk indicators that are unknown to a patient's GP. In most cases, however, the detection of hypertension or cholesterol > or = 6.5 mmol/l did not lead to interventions by the GP. More efforts are needed to ensure that the beneficial effects of these interventions are not limited to participants in clinical trials but can be extended to patients in general practice.

Prevalence of trypanosomiasis in cattle in south-west Zambia.

A trypanosomiasis survey was conducted in South-West Zambia. From a total of 3,346 cattle sampled 342 cattle showed a positive trypanosomiasis parasitaemia. During the survey trypanosome species and PCV values were also recorded. With simple statistical analysis populations with higher and lower prevalence rates were differentiated. The results indicated that the Kwando River Basin Tsetse Fly Belt and the Kafue River Basin Tsetse Fly Belt infested a larger area than originally assumed and that a link-up between both belts occurred or will occur in the near future.

A study of the lecithin/sphingomyelin ratio of amniotic fluid.

1. There is a significant correlation between lecithin/sphingomyelin (L/S) ratios based on densitometry (L/S)D and L/S ratios based on phosphorus determinations ((L/S)P). 2. The fetal lung is mature when the (L/S)D, determined according to Verhoeven, A.G.J. and Merkus, H.M.W.M. (1974) Clin. Chim. Acta 53, 229--232, is 1.2. This value is equivalent to an (L/S)P of 1.8. 3. The acetone precipitation procedure, introduced by Gluck, L., Kulovich, M.V., Borer, R.C. and Keidel, W.N. (1974) Am. J. Obstet. Gynecol. 120, 142--155, is a necessary step for isolating surface-active lecithin. 4. Standardization of the (L/S)D test is feasible and should permit different laboratories to use the same transition point.

A method for the determination of sphingomyelinase activity.

A method is presented for the determination of the activity of sphingomyelinase. It is based on the determination of sphingomyelin before and after enzymatic conversion with the aid of a quantitative paper chromatographic analysis of phospholipids. This method is used for the determination of sphingomyelinase activity in various tissues such as those of the human brain and liver and fibroblast cultures. Normal values are presented.