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Fundamental aspects of ferroelectric HfO 2 , a fluorite-type oxide, are not understood yet. This is evident by different theories regarding, e.g., the wake-up effect or the antiferroelectric-like behavior of HfO 2 manufactured with different doping or deposition techniques. Therefore, we focus on sputtered and undoped HfO 2 to gain deeper understanding of the ferroelectric properties of pure HfO 2. A temperature gradient on a 10 × 10 mm 2 substrate during rapid thermal annealing led to different ferroelectric device performances in terms of remnant polarization and the wake-up effect. The results from the electrical characterization are compared to observations by transmission electron microscopy, performed on pristine and trained samples in plan-view as well as in cross section. We observed that different temperature treatments caused effects at the interfaces of the TiN electrodes and also affected the microstructure and defect concentration of the HfO 2 itself. Devices from the hot corner showed wake-up free ferroelectricity with a remnant polarization below 10 μ C / cm 2 , whereas devices from the cold corner showed a strong wake-up effect with remnant polarization starting from 0 to above 20 μ C / cm 2 after 10 6 cycles. After observing a small structural transformation in trained devices, we attributed this strong wake-up effect to gradual ferroelastic switching of pristine [110] oriented grains with in-plane polarization to partially out-of-plane polarization, while the predominantly ⟨ 111 ⟩ oriented grains in the hot corner can suppress the wake-up effect. [ABSTRACT FROM AUTHOR]

EphrinB2 regulates synaptic transmission and morphology however its role in memory formation is unknown. Here we show that deleting ephrinB2 from excitatory neurons in the basolateral amygdala (BLA) of male mice impairs long-term (LTM), but not short-term (STM), fear memory formation. Deleting ephrinB2 from astrocytes in the BLA impairs fear LTM but not STM. Removing ephrinB2 from astrocytes in the BLA reduces the level of the excitatory amino acid transporter 1 (EAAT1) in these cells. Inhibiting EAAT1 activity in the BLA during fear conditioning, by its specific inhibitor UCPH-101, impairs fear LTM showing that EAAT1 in the BLA is needed for fear LTM formation. The administration of ephrinB2 into the BLA during fear conditioning training enhances fear LTM. Moreover, ephrinB2 increases the ability of fear conditioning to activate cells in the BLA as detected by c-Fos labeling. EphrinB2 therefore determines the threshold for fear memory formation. In contrast to mature neurons, we show that ephrinB2 in neural stem cells (NSCs) is not needed for fear LTM. Our study shows that ephrinB2 in the BLA determines the strength of long-term memory consolidation., (© 2024. The Author(s).)

Many brain diseases lead to a reduction in the number of functional neurons and it would be of value to be able to increase the number of neurons in the affected brain areas. In this study, we examined whether we can promote neural stem cells to produce mature neurons and whether an increase in the mature neurons can affect cognitive performance. We detected that the EphB2 receptor is localized in immature basolateral amygdala (BLA) neurons. We therefore aimed to increase the level of EphB2 activity in neural stem cells (NSCs) in the BLA and examine the effects on the production of mature neurons and cognition. Toward that end, we utilized a photoactivatable EphB2 construct (optoEphB2) to increase EphB2 forward signaling in NSCs in the BLA. We revealed that the activation of optoEphB2 in NSCs in the BLA increased the level of immature and mature neurons in the BLA. We further found that activation of optoEphB2 in BLA NSCs enhanced auditory, but not contextual, long-term fear memory formation. Impairing EphB2 forward signaling did not affect the level of immature and mature neurons in the BLA. This study provides evidence that NSCs can be promoted to produce mature neurons by activating EphB2 to enhance specific brain functions., (© 2024. The Author(s).)

Training rodents in a particularly difficult olfactory-discrimination (OD) task results in the acquisition of the ability to perform the task well, termed 'rule learning'. In addition to enhanced intrinsic excitability and synaptic excitation in piriform cortex pyramidal neurons, rule learning results in increased synaptic inhibition across the whole cortical network to the point where it precisely maintains the balance between inhibition and excitation. The mechanism underlying such precise inhibitory enhancement remains to be explored. Here, we use brain slices from transgenic mice (VGAT-ChR2-EYFP), enabling optogenetic stimulation of single GABAergic neurons and recordings of unitary synaptic events in pyramidal neurons. Quantal analysis revealed that learning-induced enhanced inhibition is mediated by increased quantal size of the evoked inhibitory events. Next, we examined the plasticity of synaptic inhibition induced by long-lasting, intrinsically evoked spike firing in post-synaptic neurons. Repetitive depolarizing current pulses from depolarized (-70 mV) or hyperpolarized (-90 mV) membrane potentials induced long-term depression (LTD) and long-term potentiation (LTP) of synaptic inhibition, respectively. We found a profound bidirectional increase in the ability to induce both LTD, mediated by L-type calcium channels, and LTP, mediated by R-type calcium channels after rule learning. Blocking the GABA B receptor reversed the effect of intrinsic stimulation at -90 mV from LTP to LTD. We suggest that learning greatly enhances the ability to modify the strength of synaptic inhibition of principal neurons in both directions. Such plasticity of synaptic plasticity allows fine-tuning of inhibition on each particular neuron, thereby stabilizing the network while maintaining the memory of the rule. KEY POINTS: Olfactory discrimination rule learning results in long-lasting enhancement of synaptic inhibition on piriform cortex pyramidal neurons. Quantal analysis of unitary inhibitory synaptic events, evoked by optogenetic minimal stimulation, revealed that enhanced synaptic inhibition is mediated by increased quantal size. Surprisingly, metaplasticity of synaptic inhibition, induced by intrinsically evoked repetitive spike firing, is increased bidirectionally. The susceptibility to both long-term depression (LTD) and long-term potentiation (LTP) of inhibition is enhanced after learning. LTD of synaptic inhibition is mediated by L-type calcium channels and LTP by R-type calcium channels. LTP is also dependent on activation of GABA B receptors. We suggest that learning-induced changes in the metaplasticity of synaptic inhibition enable the fine-tuning of inhibition on each particular neuron, thereby stabilizing the network while maintaining the memory of the rule., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Oral health is an essential component of a person's general health and well-being. It is influenced by many factors. These include individual aspects such as oral health literacy and oral health behaviour. The aim of this study was to investigate the association between oral health literacy and behaviour with physical oral health., Methods: In this population-based cross-sectional study, data of 5510 subjects enrolled in the Hamburg City Health Study (HCHS) from 2016 to 2018 with a mean age of 62.1 years and 50.7% women were evaluated. Physical oral health was assessed using the 14-item Physical Oral Health Index (PhOX). A newly developed 10-item questionnaire based on the Oral Health Literacy Adult Questionnaire and the 5th German Oral Health Study were used to determine oral health literacy and behaviour., Results: The sum score of the 10 questions related to oral health literacy and behaviour significantly correlated with the PhOX sum score (r = 0.23; p < 0.001). An increase of one point in the total score of oral health literacy and behaviour was associated with an increase in the PhOX sum score of 1.45 points on average. This association decreased only marginally after integrating potential confounders such as age and education., Conclusion: Higher oral health literacy and better oral health behaviour are associated with better physical oral health. Oral health literacy and behaviour should be important targets in dental education to efficiently and sustainably improve the oral health of the general population., (© 2023. The Author(s).)

Long-term memory formation leads to enduring alterations in synaptic efficacy and neuronal responses that may be created by changes in neuronal morphology. We show that fear conditioning leads to a long-lasting increase in the volume of the primary and secondary dendritic branches, but not of distal branches, of neurons located at the basolateral amygdala (BLA). The length of the dendritic branches is not affected by fear conditioning. Fear conditioning leads to an enduring increase in the length and volume of dendritic spines, especially in the length of the spine neck and the volume of the spine head. Fear conditioning does not affect dendritic spine density. We further reveal that activation of Rac1 in BLA during fear conditioning impairs long-term auditory, but not contextual, fear conditioning memory. Activation of Rac1 during fear conditioning prevents the enduring increase in the dendritic primary branch volume and dendritic spines length and volume. Rac1 activation per se has no effect on neuronal morphology. These results show that fear conditioning induces changes known to reduce the inhibition of signal propagation along the dendrite and the increase in synaptic efficacy whereas preventing these changes, by Rac1 activation, impairs fear memory formation., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

This paper presents a measurement setup which is able to measure the distribution of small scale pressure on an area of 15.2 mm × 30.4 mm with a sample rate up to 1.2 kHz. It was used to investigate the contact pressures of vocal folds during phonation. This was performed in ex vivo experiments of 11 porcine larynges. The contact pressure at the medial surface and other phonation parameters, as the glottal resistance and the closing velocity of the vocal fold, were measured at different adduction and elongation levels and air flow rates. A statistical analysis was carried out. It could be shown that the contact pressure rises, when the vocal fold is manipulated or when the flow rate is increased., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Alterations in mRNA transcription have been associated with changes in brain functions. We wanted to examine if fear conditioning causes long-term changes in transcriptome profiles in the basolateral amygdala (BLA) and hippocampus using RNA-Seq and laser microdissection microscopy. We further aimed to uncover whether these changes are involved in memory formation by monitoring their levels in EphB2 lacZ/lacZ mice, which lack EphB2 forward signaling and can form short-term fear conditioning memory but not long-term fear conditioning memory. We found transcriptome signatures unique to each brain region that are comprise of specific cellular pathways. We also revealed that fear conditioning leads to alterations in mRNAs levels 24 h after training in hippocampal neuropil, but not in hippocampal cell layers or BLA. The two main groups of altered mRNAs encode proteins involved in neuronal transmission, neuronal morphogenesis and neuronal development and the vast majority are known to be enriched in neurons. None of these mRNAs levels were altered by fear conditioning in EphB2 lacZ/lacZ mice, which were also impaired in long-term fear memory. We show here that fear conditioning leads to an enduring alteration in mRNAs levels in hippocampal neuropil that is dependent on processes mediated by EphB2 that are needed for long-term memory formation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Visiting a dentist can be an unpleasant experience for many people. Especially clinical procedures for provision of fixed dental prostheses (FDP) can be burdensome. The aim of this study was to assess the impact of media entertainment via flat screens on the ceiling on patient experiences during dental treatment for FDP., Methods: In this randomized controlled clinical trial (RCT), a sample of 145 patients (mean age: 42.7 years, 55.2% female) undergoing treatment for FDP was recruited and randomly assigned to intervention group (n = 69) with media entertainment or control group without media (n = 76). Perceived burdens were assessed with the 25-item Burdens in Prosthetic Dentistry Questionnaire (BiPD-Q). Total and dimension scores can range from 0 to 100 with higher scores representing higher burdens. Impact of media entertainment on perceived burdens was assessed using t-test and multivariate linear regression analysis. Effect sizes (ES) were calculated., Results: Perceived burdens were in general quite low indicated by a mean BiPD-Q total score of 24.4 points, with highest scores for the domain preparation (28.9) and lowest for global treatment aspects (19.8). Media entertainment had a significant effect on overall perceived burdens with lower scores in the intervention group (20.0) than in the control group (29.2; ES: 0.54; p = 0.002). Highest impact was observed for the domains global treatment aspects (ES: 0.61; p < 0.001) and impression (ES: 0.55; p = 0.001), and lowest for anesthesia (ES: 0.27; p = 0.103)., Conclusion: Media entertainment on flat screens during dental treatments decreases perceived burdens and may provide patients a less unpleasant treatment experience., Clinical Significance: Long and invasive treatments as performed for providing fixed dental prostheses may induce substantial burdens to the patients. Media entertainment on a flat screen TV on the ceiling has a significant attenuating effect on patients and significantly reduces perceived burdens, and subsequently improves process-related quality of care in dentistry., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: The vibration of the vocal folds produces the primary sound for the human speech. The vibration depends mainly on the pressure, airflow of the lungs, and the material properties of the vocal folds. In order to change them, muscles in the larynx stretch the vocal folds. This interplay is rarely investigated, but can give insight in the complex process of speech production. Most material properties studies are damaging the tissue; therefore, a nondestructive one is desired., Methods: An ex vivo phonation experiment combined with the dynamic Pipette Aspiration Technique is used to investigate 10 porcine larynges, under manipulations of different adduction and elongation levels. For each manipulation, the near surface material properties of the vocal folds are measured as well as different phonation parameters like the subglottal pressure, glottal resistance, frequency, and stiffness. Thereby, a high-speed camera was used to record the vocal fold movement., Results: On most of the measured parameters, the manipulations do show an effect. Both manipulations lead to a higher phonation frequency and an increase of the stiffness of the tissue. Comparing both manipulations, the elongation results in higher elasticity values than the adduction. Different measurement parameters have been compared with each other and correlations could be found. Where the strongest correlation are found among the elasticity values of different frequencies. But it can also be seen that the elasticity values correlate with phonation parameters., Conclusion: It was possible to produce a data set of 560 measurements in total. To our knowledge, this is the first time Pipette Aspiration Technique was combined with ex vivo phonation measurements for combined measurements. The amount of measurement data made it possible to carry out statistic investigations. The effect of the manipulations on material properties as well as on phonation parameters could be measured and different correlations could be found. The results lead to the hypothesis that the stretch does not have a huge effect on the material properties of the lamina propria, but more on the underlying muscle., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The elastic properties of the vocal folds have great influence on the primary sound and thus on the entire subsequent phonation process. Muscle contractions in the larynx can alter the elastic properties of the vocal fold tissue. Quasi-static ultrasound elastography is a non-destructive examination method that can be applied to ex-vivo vocal folds. In this work, porcine vocal folds were passively elongated and adducted and the changes of the elastic properties due to that manipulations were measured., Methods: Manipulations were performed by applying force to sewn-in sutures. Elongation was achieved by a suture attached to the thyroid cartilage, which was pulled forward by defined weights. Adduction was effected by two sutures exerting torque on the arytenoid cartilage. A series of ten specimens was examined and evaluated using a quasi-static elastography algorithm. In addition, the surface stretch was measured optically using tattooed reference points., Results: This study showed that the expected stiffening of the tissue during the manipulations can be measured using quasi-static ultrasound elastography. The measured effect of elongation and adduction, both of which result in stretching of the tissue, is stiffening. However, the relative change of specific manipulations is not the same for the same load on different larynges, but is rather related to stretch caused and other uninvestigated factors., Conclusion: The passive elongation and adduction of vocal folds stiffen the tissue of the vocal folds and can be measured using ultrasound elastography., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Fear conditioning leads to long-term fear memory formation and is a model for studying fear-related psychopathological conditions such as phobias and post-traumatic stress disorder. Long-term fear memory formation is believed to involve alterations of synaptic efficacy mediated by changes in synaptic transmission and morphology in lateral amygdala (LA). Nck1 is a key neuronal adaptor protein involved in the regulation of the actin cytoskeleton and the neuronal processes believed to be involved in memory formation. However, the role of Nck1 in memory formation is not known. Here we explored the role of Nck1 in fear memory formation in lateral amygdala (LA). Reduction of Nck1 in excitatory neurons in LA enhanced long-term, but not short-term, auditory fear conditioning memory. Activation of Nck1, by using a photoactivatable Nck1 (PA-Nck1), during auditory fear conditioning in excitatory neurons in LA impaired long-term, but not short-term, fear memory. Activation of Nck1 immediately or a day after fear conditioning did not affect fear memory. The hippocampal-mediated contextual fear memory was not affected by the reduction or activation of Nck1 in LA. We show that Nck1 is localized to the presynapses in LA. Nck1 activation in LA excitatory neurons decreased the frequency of AMPA receptors-mediated miniature excitatory synaptic currents (mEPSCs). Nck1 activation did not affect GABA receptor-mediated inhibitory synaptic currents (mIPSCs). These results show that Nck1 activity in excitatory neurons in LA regulates glutamate release and sets the threshold for fear memory formation. Moreover, our research shows that Nck1 may serve as a target for pharmacological treatment of fear and anxiety disorders., (© 2022. The Author(s).)

Fear memory may undergo a process after memory reactivation called reconsolidation. To examine the roles of ephrinA4 in fear memory reconsolidation an inhibitory ephrinA4 mimetic peptide (pep-ephrinA4), that targets the EphA binding site and inhibits EphA activation, was used. Pep-ephrinA4 was microinjected into the lateral amygdala (LA) of fear-conditioned rats 24 h after training and 30 min before tone CS memory retrieval. Memory retrieval was unaffected by pep-ephrinA4. However, the animals were impaired in fear memory tested 1 h or 24 h afterward when compared to controls. Fear-conditioned animals injected with pep-ephrinA4 into LA immediately after long-term memory retrieval were unaffected when tested 24 h afterward. Microinjection into LA of a peptide originated from an ephrinA4 site that does not interact with EphA did not affect fear memory reconsolidation. Rats that were administrated with pep-ephrinA4 systemically 24 h after fear conditioning and 30 min before CS memory retrieval were impaired in long-term fear conditioning memory tested 24 h afterward when compared to the control peptide. These results show that ephrinA4 binding sites are needed for long-term fear memory reconsolidation in LA and may serve as a target for the treatment of fear-related disorders by blocking reconsolidation., (© 2022. The Author(s).)

Aim: Aim of this study was to investigate the association between periodontitis and arterial hypertension, both of which show correlations with classical cardiovascular risk factors and inflammatory activity., Materials and Methods: A cross-sectional analysis of data from a large population-based health survey (the Hamburg City Health Study, HCHS) including 5934 participants with complete periodontal examination and blood pressure data, of whom 5735 had medical records regarding anti-hypertensive medication, was performed. Probing depths, gingival recessions, bleeding on probing (BOP), dental plaque, and decayed-missing-filled teeth (DMFT) indices were recorded as measures of oral health. Clinical attachment loss (CAL) per tooth was calculated and periodontitis was staged into three groups (no/mild, moderate, severe). Arterial hypertension was diagnosed based on the participants' medication history and systolic and diastolic blood pressure values. Logistic regression models were constructed accounting for a set of potential confounders (age, sex, smoking, body mass index (BMI), diabetes, educational level, alcohol intake) and high sensitivity-C-reactive protein (hsCRP)., Results: The odds of arterial hypertension increased significantly along with periodontitis severity (OR for severe periodontitis: 2.19; 95% CI 1.85-2.59; p < 0.001; OR for moderate periodontitis: 1.65; 95% CI 1.45-1.87; p < 0.001). Participants with moderate or severe periodontitis also had significantly higher age- and sex-adjusted odds of arterial hypertension, which was slightly weakened when additionally adjusted for BMI, diabetes, smoking, educational level, and alcohol intake (OR for severe PD: 1.28, 95% CI 1.04-1.59, p = 0.02; OR for moderate PD: 1.30, 95% CI 1.11-1.52, p = 0.001). The fraction of participants with undertreated hypertension (untreated and poorly controlled hypertension) was considerably larger in participants with severe periodontitis than in those with no/mild periodontitis (50.1% vs. 37.4% for no/mild periodontitis)., Conclusions: The study shows an association between periodontitis and arterial hypertension that is independent of age, sex, diabetes, BMI, smoking, educational level, and alcohol intake. In addition, undertreatment of hypertension was more common in people with severe periodontitis compared with periodontally more healthy people., (© 2022. The Author(s).)