Osteoporotic Animal Models of Bone Healing: Advantages and Pitfalls

The aim of this review was to summarize the advantages and pitfalls of the available osteoporotic animal models of bone healing. A thorough literature search was performed in MEDLINE via OVID and EMBASE to identify animal studies investigating the effect of experimental osteoporosis on bone healing and bone regeneration. The osteotomy model in the proximal tibia is the most popular osseous defect model to study the bone healing process in osteoporotic-like conditions, although other well-characterized models, such as the post-extraction model, might be taken into consideration by future studies. The regenerative potential of osteoporotic bone and its response to biomaterials/regenerative techniques has not been clarified yet, and the critical size defect model might be an appropriate tool to serve this purpose. Since an ideal animal model for simulating osteoporosis does not exist, the type of bone remodeling, the animal lifespan, the age of peak bone mass, and the economic and ethical implications should be considered in our selection process. Furthermore, the influence of animal species, sex, age, and strain on the outcome measurement should be taken into account. In order to make future studies meaningful, standardized international guidelines for osteoporotic animal models of bone healing need to be set up.     

Adverse life events, area socioeconomic disadvantage, and psychopathology and resilience in young children: the importance of risk factors’ accumulation and protective factors’ specificity

Few studies on resilience in young children model risk appropriately and test theory-led hypotheses about its moderation. This study addressed both issues. Our hypothesis was that for preschool children’s emotional/behavioral adjustment in the face of contextual risk protective factors should be located in the cognitive domain. Data were from the first two sweeps of the UK’s Millennium Cohort Study. The final study sample was 4,748 three-year-old children clustered in 1,549 Lower layer Super Output Areas in nine strata. Contextual risk was measured at both area (with the Index of Multiple Deprivation) and family (with proximal and distal adverse life events experienced) level. Moderator variables were parenting, verbal and non-verbal ability, developmental milestones, and temperament. Multivariate multilevel models—that allowed for correlated residuals at both individual and area level—and univariate multilevel models estimated risk effects on specific and broad psychopathology. At baseline, proximal family risk, distal family risk and area risk were all associated with broad psychopathology, although the most parsimonious was the proximal family risk model. The area risk/broad psychopathology association remained significant even after family risk was controlled but not after family level socioeconomic disadvantage was controlled. The cumulative family risk was more parsimonious than the specific family risks model. Non-verbal ability moderated the effect of proximal family risk on conduct and emotional problems, and developmental milestones moderated the effect of proximal family risk on conduct problems. The findings highlight the importance of modeling contextual risk appropriately and of locating in the cognitive domain factors that buffer its effect on young children’s adjustment.     

How not to study spontaneous activity

Brains are restless. We have long known of the existence of a great deal of uninterrupted brain activity that maintains the body in a stable state — from an evolutionary standpoint one of the brain's most ancient tasks. But intrinsic, ongoing activity is not limited to subcortical, life-maintaining structures; cortex, too, is remarkably active even in the absence of a sensory stimulus or a specific behavioral task. This is evident both in its enormous energy consumption at rest and in the large, spontaneous but coherent fluctuations of neural activity that spread across different areas. Not surprisingly, a growing number of electrophysiological and functional magnetic resonance imaging (fMRI) studies are appearing that report on various aspects of the brain's spontaneous activity or “default mode” of operation.One recent study reports results from simultaneously combined electrophysiological and fMRI measurements in the monkey visual cortex (Shmuel, A., Leopold, D.A., 2008. Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: implications for functional connectivity at rest. Hum. Brain Mapp. 29, 751–761). The authors claim to be able to demonstrate correlations between slow fluctuations in blood-oxygen-level-dependent (BOLD) signals and concurrent fluctuations in the underlying, locally measured neuronal activity. They even go on to speculate that the fluctuations display wave-like spatiotemporal patterns across cortex. In the present report, however, we re-analyze the data presented in that study and demonstrate that the measurements were not actually taken during rest. Visual cortex was subject to almost imperceptible but physiologically clearly detectable flicker induced by the visual stimulator. An examination of the power spectral density of the neural responses and the neurovascular impulse response function shows that such imperceptible flicker strongly suppresses the slow oscillations and changes the degree of covariance between neural and vascular signals. In addition, a careful analysis of the spatiotemporal patterns demonstrates that no slow waves of activity exist in visual cortex; instead, the presented wave data reflect differences in signal-to-noise ratio at various cortical sites due to local differences in vascularization. In this report, assuming that the term “spontaneous activity” refers to intrinsic physiological processes at the absence of sensory inputs or motor outputs, we discuss the need for careful selection of experimental protocols and of examining the degree to which the activation of sensory areas might influence the cortical or subcortical processes in other brain regions.     

Millisecond encoding precision of auditory cortex neurons

Neurons in auditory cortex are central to our perception of sounds. However, the underlying neural codes, and the relevance of millisecond-precise spike timing in particular, remain debated. Here, we addressed this issue in the auditory cortex of alert nonhuman primates by quantifying the amount of information carried by precise spike timing about complex sounds presented for extended periods of time (random tone sequences and natural sounds). We investigated the dependence of stimulus information on the temporal precision at which spike times were registered and found that registering spikes at a precision coarser than a few milliseconds significantly reduced the encoded information. This dependence demonstrates that auditory cortex neurons can carry stimulus information at high temporal precision. In addition, we found that the main determinant of finely timed information was rapid modulation of the firing rate, whereas higher-order correlations between spike times contributed negligibly. Although the neural coding precision was high for random tone sequences and natural sounds, the information lost at a precision coarser than a few milliseconds was higher for the stimulus sequence that varied on a faster time scale (random tones), suggesting that the precision of cortical firing depends on the stimulus dynamics. Together, these results provide a neural substrate for recently reported behavioral relevance of precisely timed activity patterns with auditory cortex. In addition, they highlight the importance of millisecond-precise neural coding as general functional principle of auditory processing—from the periphery to cortex.     

Modeling risks: effects of area deprivation, family socio-economic disadvantage and adverse life events on young children’s psychopathology

Background  

The effects of contextual risk on young children’s behavior are not appropriately modeled.     

A preliminary morphometric magnetic resonance imaging study of regional brain volumes in body dysmorphic disorder

Morphometric magnetic resonance imaging (MRI) was used to compare regional brain volumes in eight women with body dysmorphic disorder (BDD) and eight healthy comparison subjects. The BDD group exhibited a relative leftward shift in caudate asymmetry and greater total white matter vs. the comparison group. Findings with respect to the caudate nucleus are consistent with both the conceptualization of BDD as an obsessive-compulsive spectrum disorder, and the 'striatal topography model' of obsessive-compulsive disorders.     

Karyotypic abnormalities in tumours of the pancreas.

Short-term cultures from 20 pancreatic tumours, three endocrine and 17 exocrine, were cytogenetically analysed. All three endocrine tumours had a normal chromosome complement. Clonal chromosome aberrations were detected in 13 of the 17 exocrine tumours: simple karyotypic changes were found in five carcinomas and numerous numerical and/or structural changes in eight. When the present findings and those previously reported by our group were viewed in conjunction, the most common numerical imbalances among the 22 karyotypically abnormal pancreatic carcinomas thus available for evaluation turned out to be, in order of falling frequency, -18, -Y, +20, +7, +11 and -12. Imbalances brought about by structural changes most frequently affected chromosomes 1 (losses in 1p but especially gains of 1q), 8 (in particular 8q gains but also 8p losses), and 17 (mostly 17q gain but also loss of 17p). Chromosomal bands 1p32, 1q10, 6q21, 7p22, 8p21, 8q11, 14p11, 15q10-11, and 17q11 were the most common breakpoint sites affected by the structural rearrangements. Abnormal karyotypes were detected more frequently in poorly differentiated and anaplastic carcinomas than in moderately and well differentiated tumours.     

Translation and validation of the Depression Outcomes Module (DOM) in Greece

In Greece, as in other countries, major depressive disorder is underdiagnosed. Its severity, implications and outcomes are often not adequately evaluated. The Depression Outcomes Module (DOM) was developed in order to meet the need for a global assessment of this disorder. The objective of the current study was to estimate the psychometric properties of DOM in a Greek population presenting depressive symptoms. The DOM was translated into Greek. Patients were examined twice (baseline and follow-up assessment). The psychometric properties of DOM were calculated. Subjects were 83 psychiatric inpatients and outpatients presenting depressive symptoms. The measures used were DOM, Structured Clinical Interview for DSM III-R (SCID) and Hamilton Rating Scale for Depression (Ham-D). The results were: (a) baseline assessment: test-retest reliability k = 0.90, internal consistency 0.93, sensitivity 97%, specificity 90%; (b) follow up assessment: test-retest reliability k = 0.89, sensitivity 81% and specificity 67%. Recovery from depression detected by DOM at the follow-up was significantly correlated both with pharmacotherapy and with a combination of pharmacotherapy and supportive psychotherapy. It was concluded that the Greek version of DOM is a comprehensive, useful instrument for diagnosing, assessing depression and evaluating its outcomes.