Brain network efficiency and topology depend on the fiber tracking method: 11 tractography algorithms compared in 536 subjects

As connectivity analyses become more popular, claims are often made about how the brain's anatomical networks depend on age, sex, or disease. It is unclear how results depend on tractography methods used to compute fiber networks. We applied 11 tractography methods to high angular resolution diffusion images of the brain (4-Tesla 105-gradient HARDI) from 536 healthy young adults. We parcellated 70 cortical regions, yielding 70×70 connectivity matrices, encoding fiber density. We computed popular graph theory metrics, including network efficiency, and characteristic path lengths. Both metrics were robust to the number of spherical harmonics used to model diffusion (4th-8th order). Age effects were detected only for networks computed with the probabilistic Hough transform method, which excludes smaller fibers. Sex and total brain volume affected networks measured with deterministic, tensor-based fiber tracking but not with the Hough method. Each tractography method includes different fibers, which affects inferences made about the reconstructed networks.

Multiple stages classification of Alzheimer’s disease based on structural brain networks using generalized low rank approximations (GLRAM)

To classify each stage for a progressing disease such as Alzheimer’s disease is a key issue for the disease prevention and treatment. In this study, we derived structural brain networks from diffusion-weighted MRI using whole-brain tractography since there is growing interest in relating connectivity measures to clinical, cognitive, and genetic data. Relatively little work has usedmachine learning to make inferences about variations in brain networks in the progression of the Alzheimer’s disease. Here we developed a framework to utilize generalized low rank approximations of matrices (GLRAM) and modified linear discrimination analysis for unsupervised feature learning and classification of connectivity matrices. We apply the methods to brain networks derived from DWI scans of 41 people with Alzheimer’s disease, 73 people with EMCI, 38 people with LMCI, 47 elderly healthy controls and 221 young healthy controls. Our results show that this new framework can significantly improve classification accuracy when combining multiple datasets; this suggests the value of using data beyond the classification task at hand to model variations in brain connectivity.

Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human

Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telomere integrity. NMR, as well as human, was also found to have a lower rate of germline nucleotide substitution than the mouse. Together, the data suggest that the long-lived NMR, as well as human, has more robust GM than mouse and identifies new targets for the analysis of the exceptional longevity of the NMR.

Letter: Brain natriuretic peptide is a potentially useful screening tool for the detection of cardiovascular disease in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have a significantly higher risk of coronary heart disease, despite being less likely to report symptoms of angina, and are more likely to experience unrecognised myocardial infarction and sudden cardiac death than non-RA controls.1 Furthermore, left ventricular diastolic dysfunction has been described in up to 40% of patients with RA.2...

The effects of osteoporosis on osseointegration in the rat maxilla

The study investigated the effects of oestrogen deficiency on dental implant in a rat model. An osteoporosis rat model was successfully established for dental implant research and it was noted that bone cells functioned differently in osteoporotic condition during the healing of dental implant. The study further demonstrated that implant surface roughness could stimulate bone formation, therefore, improve the bone healing in osteoporotic condition.

Adjustable stiffness, external fixator for the rat femur osteotomy and segmental bone defect models

The mechanical environment around the healing of broken bone is very important as it determines the way the fracture will heal. Over the past decade there has been great clinical interest in improving bone healing by altering the mechanical environment through the fixation stability around the lesion. One constraint of preclinical animal research in this area is the lack of experimental control over the local mechanical environment within a large segmental defect as well as osteotomies as they heal. In this paper we report on the design and use of an external fixator to study the healing of large segmental bone defects or osteotomies. This device not only allows for controlled axial stiffness on the bone lesion as it heals, but it also enables the change of stiffness during the healing process in vivo. The conducted experiments have shown that the fixators were able to maintain a 5 mm femoral defect gap in rats in vivo during unrestricted cage activity for at least 8 weeks. Likewise, we observed no distortion or infections, including pin infections during the entire healing period. These results demonstrate that our newly developed external fixator was able to achieve reproducible and standardized stabilization, and the alteration of the mechanical environment of in vivo rat large bone defects and various size osteotomies. This confirms that the external fixation device is well suited for preclinical research investigations using a rat model in the field of bone regeneration and repair.

Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging

Here we describe a protocol for advanced CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis). The CUBIC protocol enables simple and efficient organ clearing, rapid imaging by light-sheet microscopy and quantitative imaging analysis of multiple samples. The organ or body is cleared by immersion for 1–14 d, with the exact time required dependent on the sample type and the experimental purposes. A single imaging set can be completed in 30–60 min. Image processing and analysis can take <1 d, but it is dependent on the number of samples in the data set. The CUBIC clearing protocol can process multiple samples simultaneously. We previously used CUBIC to image whole-brain neural activities at single-cell resolution using Arc-dVenus transgenic (Tg) mice. CUBIC informatics calculated the Venus signal subtraction, comparing different brains at a whole-organ scale. These protocols provide a platform for organism-level systems biology by comprehensively detecting cells in a whole organ or body.

Physical activity cost in children following an acquired brain injury : a comparative study

Background: Alterations in energy expenditure during activity post head injury has not been investigated due primarily to the difficulty of measurement. Objective: The aim of this study was to compare energy expenditure during activity and body composition of children following acquired brain injury (ABI) with data from a group of normal controls. Design: Energy expenditure was measured using the Cosmed K4b2 in a group of 15 children with ABI and a group of 67 normal children during rest and when walking and running. Mean number of steps taken per 3 min run was also recorded and body composition was measured. Results: The energy expended during walking was not significantly different between both groups. A significant difference was found between the two groups in the energy expended during running and also for the number of steps taken as children with ABI took significantly less steps than the normal controls during a 3 min run. Conclusions: Children with ABI exert more energy per activity than healthy controls when controlled for velocity or distance. However, they expend less energy to walk and run when they are free to choose their own desirable, comfortable pace than normal controls. © 2003 Elsevier Ltd. All rights reserved.

Doctor’s knowledge and practices of traumatic brain injury management in Chinese prehospital settings

Objectives: The incidence and mortality of traumatic brain injury (TBI) has increased rapidly in the last decade in China. Appropriate ambulance service can reduce case-fatality rates of TBI significantly. This study aimed to explore the factors (age, gender, education level, clinical experience, professional title, organization, specialty before prehospital care, and training frequency) that could influence prehospital doctors’ knowledge level and practices in TBI management in China, Hubei Province. Methods: A cross-sectional questionnaire survey was conducted in two cities in Hubei Province. The self-administered questionnaire consisted of demographic information and questions about prehospital TBI management. Independent samples t-test and one-way ANOVA were used to analyze group differences in the average scores in terms of demographic character. General linear regression was used to explore associated factors in prehospital TBI management. Results: A total of 56 questionnaires were handed out and 52 (93%) were returned. Participants received the lowest scores in TBI treatment (0.64; SD=0.08) and the highest scores in TBI assessment (0.80; SD=0.14). According to the regression model, the education level was associated positively with the score of TBI identification (P=.019); participants who worked in the emergency department (ED; P=.011) or formerly practiced internal medicine (P=.009) tended to get lower scores in TBI assessment; participants’ scores in TBI treatment were associated positively with the training frequency (P=.011); and no statistically significant associated factor was found in the overall TBI management. Conclusion: This study described the current situation of prehospital TBI management. The prehospital doctors’ knowledge level and practices in TBI management were quantified and the influential factors hidden underneath were explored. The results indicated that an appropriate continuing medical education (CME) program enables improvement of the quality of ambulance service in China.

Turning gaming EEG peripherals into trainable brain computer interfaces

Companies such as NeuroSky and Emotiv Systems are selling non-medical EEG devices for human computer interaction. These devices are significantly more affordable than their medical counterparts, and are mainly used to measure levels of engagement, focus, relaxation and stress. This information is sought after for marketing research and games. However, these EEG devices have the potential to enable users to interact with their surrounding environment using thoughts only, without activating any muscles. In this paper, we present preliminary results that demonstrate that despite reduced voltage and time sensitivity compared to medical-grade EEG systems, the quality of the signals of the Emotiv EPOC neuroheadset is sufficiently good in allowing discrimina tion between imaging events. We collected streams of EEG raw data and trained different types of classifiers to discriminate between three states (rest and two imaging events). We achieved a generalisation error of less than 2% for two types of non-linear classifiers.

Comparative genomic analysis of human Chlamydia pneumoniae isolates from respiratory, brain and cardiac tissues

Chlamydia pneumoniae is an obligate intracellular bacterium implicated in a wide range of human diseases including atherosclerosis and Alzheimer's disease. Efforts to understand the relationships between C. pneumoniae detected in these diseases have been hindered by the availability of sequence data for non-respiratory strains. In this study, we sequenced the whole genomes for C. pneumoniae isolates from atherosclerosis and Alzheimer's disease, and compared these to previously published C. pneumoniae genomes. Phylogenetic analyses of these new C. pneumoniae strains indicate two sub-groups within human C. pneumoniae, and suggest that both recombination and mutation events have driven the evolution of human C. pneumoniae. Further fine-detailed analyses of these new C. pneumoniae sequences show several genetically variable loci. This suggests that similar strains of C. pneumoniae are found in the brain, lungs and cardiovascular system and that only minor genetic differences may contribute to the adaptation of particular strains in human disease.

Fate of swallowed interleukin 8 and TNFα, and effect on the Wistar rat gut

To evaluate the passage of cytokines through the gastrointestinal tract, we investigated the digestion of interleukin-8 (IL-8) and tumour necrosis factor α (TNFα), in vitro and in vivo, and their propensity to induce intestinal inflammation. We serially immuno-assayed IL-8 and TNFα solutions co-incubated with each of three pancreatin preparations at pH 4.5 and pH 8. We gavaged IL-8, TNFα and marker into 15 Wistar rats, and measured their faecal cytokine concentrations by ELISA and histologically examined their guts. IL-8 immunoreactivity was extinguished by all pancreatin preparations after 1 h of incubation at 37 °C. TNFα concentration progressively fell from 1 to 4 h with all enzyme preparations. Buffer control samples maintained their cytokine concentrations throughout incubation. No IL-8 or TNFα was detected in any rat faecal pellets. There was no significant proinflammatory effect of the gavaged cytokines on rat intestine. IL-8 and TNFα in aqueous solution could well be fully digested in the CF gut when transit time is normal and exogenous enzymes are provided, although cytokines swallowed in viscous sputum may be protected from such digestion

Cloning and gastrointestinal expression of rat hephaestin: Relationship to other iron transport proteins

The membrane-bound ceruloplasmin homolog hephaestin plays a critical role in intestinal iron absorption. The aims of this study were to clone the rat hephaestin gene and to examine its expression in the gastrointestinal tract in relation to other genes encoding iron transport proteins. The rat hephaestin gene was isolated from intestinal mRNA and was found to encode a protein 96% identical to mouse hephaestin. Analysis by ribonuclease protection assay and Western blotting showed that hephaestin was expressed at high levels throughout the small intestine and colon. Immunofluorescence localized the hephaestin protein to the mature villus enterocytes with little or no expression in the crypts. Variations in iron status had a small but nonsignificant effect on hephaestin expression in the duodenum. The high sequence conservation between rat and mouse hephaestin is consistent with this protein playing a central role in intestinal iron absorption, although its precise function remains to be determined.

Studies of water and electrolyte movement from oral rehydration solutions (rice- and glucose-based) across a normal and secreting gut using a dual isotope tracer technique in a rat perfusion model

Aims: To establish a model to measure bidirectional flow of water from a glucose oral rehydration solution (G-ORS) and a newly developed rice-based oral rehydration solution (R-ORS) using a dual isotope tracer technique in a rat perfusion model. To measure net water, sodium and potassium absorption from the ORS. Methods: In viva steady-state perfusion studies were carried out in normal and secreting (induced by cholera toxin) rat small intestine (n = 11 in each group). To determine bidirectional flow of water from the ORS the animals were initially labelled with tritium, and deuterium was added to the perfusion solution. Sequential perfusate and blood samples were collected after attainment of steady-state conditions and analysed for water and electrolyte content. Results: There was a significant increase in net water absorption from the R-ORS compared to the G-ORS in both the normal (P < 0.02) and secreting intestine (P < 0.05). Water efflux was significantly reduced in the R-ORS group compared to the G-ORS group in both the normal (P < 0.01) and the secreting intestine (P < 0.01). There was an increase in sodium absorption in the R-ORS group compared to the G-ORS. The G-ORS produced a significantly greater blood glucose level at 75 min compared to the R-ORS (P < 0.03) in the secreting intestine. Conclusions: This study demonstrates the improved water absorption from a rice-based ORS in both the normal and secreting intestine. Evidence that the absorption of water may be influenced by the osmolality of the ORS was also demonstrated.