Association between oral infections, triglyceride-glucose index, and in-stent restenosis.

OBJECTIVES: To investigate oral infections in patients suffering in-stent restenosis (ISR) and non-ISR and analyze the possible correlation between the oral infection and triglyceride-glucose (TyG) index, a clinical surrogate indicator of insulin resistance (IR). MATERIALS AND METHODS: A cross-sectional design was used, in which 586 patients with acute coronary syndrome who underwent coronary angiography 6-24 months after coronary stent implantation were recruited. The modified total dental index (TDI) was used to evaluate the status of oral inflammation. RESULTS: In both univariate analyses, TDI scores [3 (1.5, 4.5) vs. 2.5 (1.5, 4.0), p < 0.01] and a multivariate regression model (OR = 1.202, 95% CI = 1.085-1.333, p < 0.01), the TDI significantly correlated with ISR. The TyG index was positively associated with ISR (OR = 1.766, 95% CI = 1.055-2.957, p < 0.05). Correlation analysis showed that TDI was positively correlated with TyG index (r = 0.190, p < 0.01). Using linear regression analysis, higher TDI scores were significantly associated with IR (95% CI = 0.029-0.063, p < 0.01). CONCLUSIONS: Oral infections and TyG index were independently and positively correlated with ISR in patients with acute coronary syndrome. Oral inflammatory burden assessed by TDI score was associated with IR.

What Happened in the Hippocampal Axon in a Rat Model of Posttraumatic Stress Disorder.

Studies from postmortem and animal models have revealed altered synapse morphology and function in the brain of posttraumatic stress disorder (PTSD). And the effects of PTSD on dendrites and spines have been reported, however, the effection on axon include microtubule (MT) and synaptic vesicles of presynaptic elements remains unknown. Hippocampus is involved in abnormal memory in PTSD. In the present study, we used the single prolonged stress (SPS) model to mimic PTSD. Quantitative real-time polymerase chain reaction (RT-qPCR) and high-throughput sequencing (GSE153081) were utilized to analyze differentially expressed genes (DEGs) in the hippocampus of control and SPS rats. Immunofluorescence and western blotting were performed to examine change in axon-related proteins. Synaptic function was evaluated by measuring miniature excitatory postsynaptic currents (mEPSCs). RNA-sequencing analysis revealed 230 significantly DEGs between the control and SPS groups. Gene Ontology analysis revealed upregulation in axonemal assembly, MT formation, or movement, but downregulation in axon initial segment and synaptic vesicles fusion in the hippocampus of SPS rats. Increased expression in tau, ß-tubulin MAP1B, KIF9, CCDC40, DNAH12 and decreased expression in p-tau, stathmin suggested SPS induced axon extension. Increased protein expression in VAMP, STX1A, Munc18-1 and decreased expression in synaptotagmin-1 suggested SPS induced more SNARE complex formation but decreased ability in synaptic vesicle fusion to presynaptic active zone membrane in the hippocampus of SPS rats. Further, low mEPSC frequency in SPS rats indicated dysfunction in presynaptic membrane. These results suggest that axon extension and synaptic vesicles fusion abnormality are involved in dysfunction of PTSD.

An Advanced Transcriptional Response to Corticosterone After Single Prolonged Stress in Male Rats.

Stress-related neuropsychiatric disorders are often accompanied by dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. In patients suffering from post-traumatic stress disorder (PTSD), increased sensitivity of glucocorticoid negative feedback has regularly been observed. The single prolonged stress (SPS) paradigm was developed to model increased negative feedback and other aspects of PTSD in rats. In this study, we used a setup that precluded the evaluation of negative feedback but rather served to test the hypothesis of the enhanced glucocorticoid receptor (GR) signaling in higher brain areas. We injected corticosterone or vehicle 7 days after SPS and evaluated plasma corticosterone, as well as gene expression in the dorsal hippocampus and amygdala. We observed a strikingly rapid change in the expression of established GR target genes (t = 30 min) only in the SPS group on exogenous corticosterone injection. Our results extend the notion of increased GR sensitivity in PTSD to include transcriptional responses in the hippocampus.

Effects of RU486 treatment after single prolonged stress depend on the post-stress interval.

The Single Prolonged Stress protocol is considered a model for PTSD, as it induces long lasting changes in rat behaviour and endocrine regulation. Previous work demonstrated that some of these changes can be prevented by treatment with the glucocorticoid receptor antagonist RU486, administered a week after the stressor. The current study evaluated the effects of an earlier intervention with RU486, as evaluated 1 week after SPS-exposure. Most RU486 effects occurred independent of prior stress, except for the reversal of a stress-induced increase in locomotor behaviour. The accompanying changes in gene expression depended on gene, brain region, and time. DNA methylation of the robustly down-regulated Fkbp5 gene was dissociated of changes in mRNA expression. The findings reinforce the long term effects of GR antagonist treatment, but also emphasize the need to evaluate changes over time to allow the identification of robust correlates between gene expression and behavioural/endocrine outcome of stressful experiences.

Enhanced apoptosis and decreased ampa receptors are involved in deficit in fear memory in rin1 knockout rats.

BACKGROUND: Ras and Rab interactor 1 (Rin1) is predominantly expressed in memory-related brain regions, and has been reported to play an important role in fear memory. Increased expression of Rin1 in an animal model of posttraumatic stress disorder (PTSD) has been associated with enhanced acquisition of fear memories, but the exact mechanism of Rin1 in memory regulation are not clear. METHODS: Here, we used Rin1-knockout rats to examine the effect of Rin1 on fear memories by fear conditional test and the molecular mechanisms that regulate these effects by immunofluorescence, western blotting and TUNEL. RESULTS: Our results show that Rin1-knockout rats have a deficit in formation and extinction of Auditory fear memories. Lack of Rin1 results in enhanced apoptosis in the hippocampus through a pathway related to the mitochondria rather than the endoplasmic reticulum-related pathway. Importantly, the lack of Rin1 induces a decrease in α-amino-3­hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) found in the cytoplasm, but not in those found in the membrane. Expression of CaMKII (which is important for insertion of cytoplasmic AMPAR into the membrane) and stargazin (which is important for immobilization of AMPAR in the membrane) was not changed. The lack of Rin1 also induced changes in AMPAR distribution, from diffuse spread in the cells to clusters around the edge of the cell. Additionally, clustered AMPAR distribution showed a high degree of overlap with actin distribution. CONCLUSION: These findings indicate that Rin1 affects not only apoptosis, but also the concentration and distribution pattern of AMPAR, which are important in the formation and extinction of fear memory.

Synapse impairment associated with enhanced apoptosis in post-traumatic stress disorder.

Synapse impairment is associated with post-traumatic stress disorder (PTSD), which is characterized by enhanced apoptosis in the hippocampus, amygdala, and other brain regions. However, there are no detailed studies on the relationship between apoptosis and synaptic connectivity in PTSD. In this review, we discuss results from various studies describing the synaptic changes observed in the PTSD brain. A decreased number of dendrites/spines or increased number of immature spines in the hippocampus, medial prefrontal cortex, and other brain regions has been reported. Studies on axon guidance, myelination, and the cytoskeleton suggest that PTSD may involve axon overgrowth and overbranching. Apoptosis affects synapse formation; low levels of caspase maintain the balance between growth cone attraction and repulsion and inhibit axon elongation. PTSD enhances neuronal apoptosis through caspase activation, which disrupts the balance between growth cone attraction and repulsion and alters growth cone trajectory, leading to axon mistargeting. Meanwhile, caspase activation induces dendritic pruning and dendrite degeneration. These events contribute to the formation of fewer and aberrant synapses, which is associated with enhanced apoptosis in PTSD.

Late glucocorticoid receptor antagonism changes the outcome of adult life stress.

BACKGROUND: Stressors activate a wide spectrum of interacting hormonal and neuronal systems resulting in behavioral and physiological responses, with consequences for the development of psychopathology. Several recent studies demonstrated that treatment with the glucocorticoid receptor (GR) antagonist RU486 during adulthood normalized effects of early life stress. We aimed to evaluate the potential of RU486 to reverse stress-induced changes in an animal model of adult stress. METHOD: We employed the single-prolonged stress (SPS) model as a multimodal stress exposure protocol in male rats. SPS rats and unstressed controls were treated with RU486 on days 8, 9, 10 after stress exposure and the effects of treatment were evaluated after another 4 days. We determined body weight gain, corticosterone levels, behavioral reactivity in anxiety tests, and brain gene expression of c-fos, corticosteroid receptors, drivers of the stress response and genes (epi-)genitally linked to PTSD. RESULTS: RU486 affected body weight gain, corticosterone levels and open field behavior only in SPS rats. RU486 had history-independent effects in reducing fear in the elevated plus maze and fear conditioning behavior. Gene expression analysis showed a diversity of in- and interdependent effects of stress and RU486. CONCLUSION: The effects of RU486 applied 1 week after stress and measured 4 days after treatment demonstrate that in the state of post-SPS the GR-dependence of homeostatic processes has changed. This suggests that GR-mediated processes are part of allostatic regulation after adult stress. The normalization of a number of SPS-effects after RU486 treatment reinforces the potential of targeting GR for treatment of stress-related psychopathologies.

Near field acoustic holography based on the equivalent source method and pressure-velocity transducers.

The advantage of using the normal component of the particle velocity rather than the sound pressure in the hologram plane as the input of conventional spatial Fourier transform based near field acoustic holography (NAH) and also as the input of the statistically optimized variant of NAH has recently been demonstrated. This paper examines whether there might be a similar advantage in using the particle velocity as the input of NAH based on the equivalent source method (ESM). Error sensitivity considerations indicate that ESM-based NAH is less sensitive to measurement errors when it is based on particle velocity input data than when it is based on measurements of sound pressure data, and this is confirmed by a simulation study and by experimental results. A method that combines pressure- and particle velocity-based reconstructions in order to distinguish between contributions to the sound field generated by sources on the two sides of the hologram plane is also examined.

Patch near field acoustic holography based on particle velocity measurements.

Patch near field acoustic holography (PNAH) based on sound pressure measurements makes it possible to reconstruct the source field near a source by measuring the sound pressure at positions on a surface that is comparable in size to the source region of concern. Particle velocity is an alternative input quantity for NAH, and the advantage of using the normal component of the particle velocity rather than the sound pressure as the input of conventional spatial Fourier transform based NAH and as the input of the statistically optimized variant of NAH has recently been demonstrated. This paper examines the use of particle velocity as the input of PNAH. Because the particle velocity decays faster toward the edges of the measurement aperture than the pressure does and because the wave number ratio that enters into the inverse propagator from pressure to velocity amplifies high spatial frequencies, PNAH based on particle velocity measurements can give better results than the pressure-based PNAH with a reduced number of iterations. A simulation study, as well as an experiment carried out with a pressure-velocity sound intensity probe, demonstrates these findings.

A sound field separation technique based on measurements with pressure-velocity probes (L).

It has recently been shown that statistically optimized near field acoustic holography based on measurement with an array of pressure-velocity transducers makes it possible to distinguish between sources on the two sides of the array and thus suppress the influence of a disturbing source [F. Jacobsen and V. Jaud, J. Acoust. Soc. Am. 121, 1550-1558 (2007)]. However, the suggested technique uses a transfer matrix optimized for the source under test and may be expected to perform less well when the disturbing source is not placed symmetrically on the other side of the array, and this will usually be the case. In this letter, a modified method is presented.

Sound field separation technique based on equivalent source method and its application in nearfield acoustic holography.

A technique for separating sound fields using two closely spaced parallel measurement surfaces and based on equivalent source method is proposed. The method can separate wave components crossing two measurement surfaces in opposite directions, which makes nearfield acoustic holography (NAH) applications in a field where there exist sources on the two sides of the hologram surface, in a reverberant field or in a scattered field, possible. The method is flexible in applications, simple in computation, and very easy to implement. The measurement surfaces can be arbitrarily shaped, and they are not restricted to be regular as in the traditional field separation technique. And, because the method performs field separation calculations directly in the spatial domain-not in the wave number domain--it avoids the errors and limitations (the window effects, etc.) associated with the traditional field separation technique based on the spatial Fourier transform method. In the paper, a theoretical description is first given, and the performance of the proposed field separation technique and its application in NAH are then evaluated through experiments.