A rabbit model for outer retinal atrophy caused by surgical RPE removal.

PURPOSE: We aimed to establish a rabbit model with retinal atrophy induced by an iatrogenic retinal pigment epithelium (RPE) removal, for future testing of the efficacy and safety of cell therapy strategies. METHODS: A localized detachment of the retina from the RPE/choroid layer was created in 18 pigmented rabbits. The RPE was removed by scraping with a custom-made extendable loop instrument. The resulting RPE wound was observed over a time course of 12 weeks with optical coherence tomography and angiography. After 4 days (group 1) and 12 weeks (group 2), histology was done and staining with hematoxylin and eosin, as well as immunofluorescence performed to further investigate the effects of debridement on the RPE and the overlying retina. RESULTS: Already after 4 days, we observed a closure of the RPE wound by proliferating RPE and microglia/macrophage cells forming a multilayered clump. This pattern continued over the observation time course of 12 weeks, whereby the inner and outer nuclear layer of the retina became atrophic. No neovascularization was observed in the angiograms or histology. The observed changes were limited to the site of the former RPE wound. CONCLUSIONS: Localized surgical RPE removal induced an adjacent progressive retinal atrophy. Altering the natural course of this model may serve as a basis to test RPE cell therapeutics.

Disorganized attachment in adolescence: Emotional and physiological dysregulation during the Friends and Family Interview and a conflict interaction.

The current study examined the effects of attachment on autonomy, relatedness, and emotion regulation during an attachment interview (Friends and Family Interview; FFI) and a Parent×Child Conflict interaction (Family Interaction Task; FIT) in 49 adolescents (11 to 17 years old). Disorganized adolescents displayed behaviors promoting autonomy and relatedness less frequently and at a lower extent than organized ones in the FIT with mothers but not with fathers. Disorganized adolescents also showed a steeper decrease in heart rate variability (HRV) than organized ones, during both the FFI and the FITs. Moreover, disorganized adolescents responded with a more marked increase in skin conductance level to the FIT with mothers than organized individuals. Dismissing adolescents showed behaviors promoting autonomy and relatedness less frequently and to a lesser extent than secure ones, while displaying more often behaviors undermining autonomy and relatedness in the FITs. Dismissing adolescents also showed a more pronounced decrease in HRV during the FFI than secure and preoccupied individuals; no differences were found between these groups in HRV during the FITs. The results suggest that disorganized adolescents had more difficulties in regulating their emotions during both the FFI and the FITs, whereas dismissing individuals seemed effectively challenged only during the interview.

Noradrenergic activation induced by yohimbine decreases interoceptive accuracy in healthy individuals with childhood adversity.

Acute stress affects interoception, but it remains unclear if this is due to activation of the sympatho-adreno-medullary (SAM) or hypothalamic-pituitary-adrenocortical axis. This study aimed to investigate the effect of SAM axis activation on interoceptive accuracy (IAcc). Central alpha2-adrenergic receptors represent a negative feedback mechanism of the SAM axis. Major depressive disorder and adverse childhood experiences (ACE) are associated with alterations in the biological stress systems, including central alpha2-adrenergic receptors. Here, healthy individuals with and without ACE as well as depressive patients with and without ACE (n = 114; all without antidepressant medication) were tested after yohimbine (alpha2-adrenergic antagonist) and placebo. We assessed IAcc and sensibility in a heartbeat counting task. Increases in systolic and diastolic blood pressure after yohimbine confirmed successful SAM axis activation. IAcc decreased after yohimbine only in the healthy group with ACE, but remained unchanged in all other groups (Group × Drug interaction). This effect may be due to selective upregulation of alpha2-adrenergic receptors after childhood trauma, which reduces capacity for attention focus on heartbeats. The sympathetic neural pathway including alpha2-adrenergic circuitries may be essential for mediating interoceptive signal transmission. Suppressed processing of physical sensations in stressful situations may represent an adaptive response in healthy individuals who experienced ACE.

Comparison of clinical outcomes after precut DMEK with or without dextran-containing medium compared to standard DMEK: a prospective pilot study.

PURPOSE: To investigate the clinical outcome and complication rate of precut Descemet membrane endothelial keratoplasty (DMEK) in two different culture conditions, dextran-containing and dextran-free medium, and compare the results with the current standard DMEK procedure. METHODS: A prospective study of 32 eyes suffering from Fuchs endothelial dystrophy were scheduled for DMEK with a follow-up of one year. The eyes were divided into four subgroups. Group + D (n = 7) received a precut DMEK stored in dextran-containing transport medium, and Group - D (n = 9) received a precut DMEK without dextran-containing medium. The respective fellow eyes received a standard DMEK (S) (preparation directly prior to surgery) stored in dextran-containing medium (S-D + ; n = 7) or without (S-D-; n = 9). RESULTS: Clinical outcome (visual acuity, endothelial cell count, central corneal thickness) and rebubbling rate were comparable for all four groups. None of the patients had a graft failure. CONCLUSION: The preliminary data of the pilot study show that precut liquid-bubble DMEK leads to comparable clinical results regardless of dextran-containing or dextran-free organ culture medium and is further comparable to the standard DMEK procedure.

Novel vitreous substitutes: the next frontier in vitreoretinal surgery.

PURPOSE OF REVIEW: After removing the native vitreous during vitreoretinal surgery, an adequate substitute is required to ensure homeostasis of the eye. Current clinically used endotamponades (silicone oil, gases, semifluorinated alkanes) are effective in promoting retinal reattachment, but lead to complications such as emulsification, prolonged inflammation, blurred vision, raised intraocular pressure, cataract formation or the need for revision surgery. The aim of this review is to provide an update on novel vitreous substitutes with a focus on polymer-based systems. RECENT FINDINGS: Polymeric hydrogels provide favourable properties such as high water content, optical transparency, suitable refractive indices and densities, adjustable rheological properties, injectability, biocompatibility and their ability to tamponade the retina via viscosity and swelling pressure, comparable to the native human vitreous body. Here, vitreous replacement strategies can be divided into chemically or physically crosslinked hydrogel systems that are applied as preformed or in-situ gelling matrices. SUMMARY: Several hydrogel-based vitreous substitutes have already been positively evaluated in preclinical tests and have the potential to enter the clinical phase soon.

Gastric interoception and gastric myoelectrical activity in bulimia nervosa and binge-eating disorder.

OBJECTIVE: Identifying factors that control food intake is crucial to the understanding and treatment of eating disorders characterized by binge eating. In healthy individuals, stomach distension plays an important role in the development of satiation, but gastric sensations might be overridden in binge eating. The present study investigated the perception of gastric signals (i.e., gastric interoception) and gastric motility in patients experiencing binge-eating episodes, that is, bulimia nervosa (BN) and binge-eating disorder (BED). METHOD: Twenty-nine patients with BN or BED (ED group) and 32 age-, sex-, and BMI-matched healthy controls (HC group) participated in the study. The onset of satiation and stomach fullness were assessed using a novel 2-step water load test (WLT-II). Gastric myoelectrical activity (GMA) was measured by electrogastrography (EGG) before and after ingestion of noncaloric water. RESULTS: Individuals in the ED group drank significantly more water until reporting satiation during the WLT-II. The percentage of normal gastric myoelectrical power was significantly smaller in the ED group compared to HC, and negatively related to the number of objective binge-eating episodes per week in patients with BN or BED. Power in the bradygastria range was greater in ED than in HC participants. DISCUSSION: Patients with EDs have a delayed response to satiation compared to HC participants, together with abnormal GMA. Repeated binge-eating episodes may induce disturbances to gastric motor function.

Droplet-based vitrification of adherent human induced pluripotent stem cells on alginate microcarrier influenced by adhesion time and matrix elasticity.

The gold standard in cryopreservation is still conventional slow freezing of single cells or small aggregates in suspension, although major cell loss and limitation to non-specialised cell types in stem cell technology are known drawbacks. The requirement for rapidly available therapeutic and diagnostic cell types is increasing constantly. In the case of human induced pluripotent stem cells (hiPSCs) or their derivates, more sophisticated cryopreservation protocols are needed to address this demand. These should allow a preservation in their physiological, adherent state, an efficient re-cultivation and upscaling upon thawing towards high-throughput applications in cell therapies or disease modelling in drug discovery. Here, we present a novel vitrification-based method for adherent hiPSCs, designed for automated handling by microfluidic approaches and with ready-to-use potential e.g. in suspension-based bioreactors after thawing. Modifiable alginate microcarriers serve as a growth surface for adherent hiPSCs that were cultured in a suspension-based bioreactor and subsequently cryopreserved via droplet-based vitrification in comparison to conventional slow freezing. Soft (0.35%) versus stiff (0.65%) alginate microcarriers in concert with adhesion time variation have been examined. Findings revealed specific optimal conditions leading to an adhesion time and growth surface (matrix) elasticity dependent hypothesis on cryo-induced damaging regimes for adherent cell types. Deviations from the found optimum parameters give rise to membrane ruptures assessed via SEM and major cell loss after adherent vitrification. Applying the optimal conditions, droplet-based vitrification was superior to conventional slow freezing. A decreased microcarrier stiffness was found to outperform stiffer material regarding cell recovery, whereas the stemness characteristics of rewarmed hiPSCs were preserved.

Poly(amidoamine)-alginate hydrogels: directing the behavior of mesenchymal stem cells with charged hydrogel surfaces.

The surface charge of a biomaterial represents a promising tool to direct cellular behavior, which is crucial for therapeutic approaches in regenerative medicine. To expand the understanding of how the material surface charge affects protein adsorption and mesenchymal stem cell behavior, differently charged surfaces with zeta potentials spanning from -25 mV to +15 mV were fabricated by the conjugation of poly(amidoamine) to alginate-based hydrogels. We showed that the increase of the biomaterials surface charge resulted in enhanced quantities of biologically available, surface-attached proteins. Since different surface charges were equalized after protein adsorption, mesenchymal stem cells interacted rather with diverse protein compositions instead of different surface features. Besides an enhanced cell attachment to increasingly positively charged surfaces, the cell spreading area and the expression of adhesion-related genes integrin α5 and tensin 1 were found to be increased after adhesion. Moreover, first results indicate a potential impact of the surface charge on mesenchymal stem cell differentiation towards bone and fat cells. The improved understanding of surface charge-related cell behavior has significant impact on the design of biomedical devices and artificial organs.

Altered patterns of heartbeat-evoked potentials in depersonalization/derealization disorder: neurophysiological evidence for impaired cortical representation of bodily signals.

OBJECTIVE: Core features of depersonalization/derealization disorder (DPD) are emotional numbing and feelings of disembodiment. Although there are several neurophysiological findings supporting subjective emotional numbing, the psychobiology of disembodiment remains unclear. METHODS: Heartbeat-evoked potentials (HEPs), which are considered psychophysiological indicators for the cortical representation of afferent signals originating from the cardiovascular system, were assessed in 23 patients with DPD and 24 healthy control individuals during rest and while performing a heartbeat perception task. RESULTS: Absolute HEP amplitudes did not differ between groups. Nevertheless, healthy individuals showed higher HEPs during the heartbeat perception task than during rest, whereas no such effect was found in patients with DPD (p = .031). Patients with DPD had higher total levels of salivary α-amylase than did healthy individuals (9626.6 [8200.0] versus 5344.3 [3745.8] kU min/l; p = .029), but there were no group differences in cardiovascular measures (heart rate = 76.2 [10.1] versus 74.3 [7.5] beats/min, p = .60; normalized low-frequency heart rate variability = 0.63 [0.15] versus 0.56 [0.15] normalized units, p = .099; low frequency/high frequency ratio = 249.3 [242.7] versus 164.8 [108.8], p = .10), salivary cortisol (57.5 [46.7] versus 55.1 [43.6] nmol min/l, p = .86), or cortisone levels (593.2 [260.3] versus 543.8 [257.1] nmol min/l, p = .52). CONCLUSIONS: These results suggest altered cortical representation of afferent signals originating from the cardiovascular system in patients with DPD, which may be associated with higher sympathetic tone. These findings may reflect difficulties of patients with DPD to attend to their actual bodily experiences.

Heart rate response to post-learning stress predicts memory consolidation.

Stressful experiences are often well remembered, an effect that has been explained by beta-adrenergic influences on memory consolidation. Here, we studied the impact of stress induced heart rate (HR) responses on memory consolidation in a post-learning stress paradigm. 206 male and female participants saw 52 happy and angry faces immediately before being exposed to the Cold Pressor Test or a non-stressful control procedure. Memory for the faces and their respective expression was tested twice, after 30 min and on the next day. High HR responders (in comparison to low HR responders as well as to the non-stressful control group) showed enhanced recognition memory one day after learning. Our results show that beta-adrenergic activation elicited shortly after learning enhances memory consolidation and that the stress induced HR response is a predictor for this effect.

Games, hormones, and "dark" personalities: Dark tetrad and the effects of violent gaming on aggression, cortisol, and testosterone.

We investigated how playing a violent versus non-violent video game affects cortisol and testosterone levels, whether these hormonal changes increase implicit aggressive cognition, and whether so-called Dark Tetrad personality traits (i.e., Machiavellianism, psychopathy, narcissism, everyday sadism) moderate these effects. Fifty-four men played either a violent or a non-violent video game for 25 min. Participants provided salivary samples at the beginning of the experiment (T1), after 25 min of gameplay (T2), and 20 min after gameplay ended (T3). In the violent condition, participants showed a significant decrease in cortisol levels (T1 to T2) and a significant negative trend in cortisol levels from T1 to T3. Moreover, higher Machiavellianism scores were related to a significantly stronger decrease in cortisol (T1 to T2) in this condition. In the non-violent condition, however, participants with higher scores in Machiavellianism had a higher increase in cortisol (T1 to T2). In contrast to changes in hormonal levels, there were no significant effects on implicit aggressive cognition. The present findings illustrate the complex interplay between personality, hormones, and game content, thus further specifying current notions on the effects of violent video games. Playing a violent video game can have a stress-reducing calming effect depending on personality traits such as Machiavellianism and the psychological need satisfaction associated with it. Also, the fact that VVG exposure was not automatically accompanied by an aggression-increasing effect proves that simple cause-effect models are not sufficiently specified without taking the underlying mechanisms into account.

Development and initial validation of a self-report measure to assess eating disorder-specific interoceptive perception.

Interoceptive deficits-particularly with respect to the perception of emotions, hunger, and satiety-constitute important targets for intervention in eating disorders (EDs). Suitable self-report measures to identify these deficits, however, are lacking. We, therefore, developed and validated a multidimensional questionnaire to assess eating disorder-specific interoceptive perception (EDIP) in terms of the ability to perceive and discriminate between emotions, hunger, and satiety. In two independent samples with a total of 2058 individuals (22.74% with self-reported EDs), exploratory and confirmatory factor analyses revealed a four-factor solution of the EDIP Questionnaire (EDIP-Q) with the subscales Emotions, Hunger, Satiety, and Discrimination. The EDIP-Q has sound psychometric properties and was related to convergent questionnaires but unrelated to divergent self-report measures, supporting its construct validity. Participants with self-reported EDs had significantly lower EDIP-Q scores compared to participants without self-reported ED diagnosis. While individuals with self-reported anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) report similar difficulties in perceiving emotions, participants with BN and BED report greater difficulties in perceiving satiety and differentiating between hunger and emotional states compared to participants with AN. In contrast, individuals with AN report higher sensibility to satiety but lower sensibility to hunger compared to individuals with BN and BED. The EDIP-Q is a valuable clinical tool to establish profiles of deficits in EDIP that provide the basis for developing more targeted treatment approaches for EDs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Photovoltaic, wireless wide-field epiretinal prosthesis to treat retinitis pigmentosa.

PURPOSE: To develop and evaluate a photovoltaic, wireless wide-field epiretinal prosthesis for the treatment of retinitis pigmentosa. METHODS: A mosaic array of thinned silicon-based photodiodes with integrated thin-film stimulation electrodes was fabricated with a flexible polyimide substrate film to form a film-based miniaturized electronic system with wireless optical power and signal transmission and integrated electrostimulation. Manufactured implants were characterized with respect to their optoelectronic performance and biocompatibility following DIN EN ISO 10993. RESULTS: A 14 mm diameter prosthesis containing 1276 pixels with a maximum sensitivity at a near infrared wavelength of 905 nm and maximized stimulation current density 30-50 µm below the electrodes was developed for direct activation of retinal ganglion cells during epiretinal stimulation. Fabricated prostheses demonstrated mucosal tolerance and the preservation of both metabolic activity, proliferation and membrane integrity of human fibroblasts as well as the retinal functions of bovine retinas. Illumination of the prosthesis, which was placed epiretinally on an isolated perfused bovine retina, with infrared light resulted in electrophysiological recordings reminiscent of an a-wave (hyperpolarization) and b-wave (depolarization). CONCLUSIONS: A photovoltaic, wireless wide-field epiretinal prosthesis for the treatment of retinitis pigmentosa using near infrared light for signal transmission was designed, manufactured and its biocompatibility and functionality demonstrated in vitro and ex vivo.

Frontal alpha asymmetry is associated with chronic stress and depression, but not with somatoform disorders.

Cardinal characteristics of somatoform disorders (SFDs) are worry of illness, and impaired affective processing. We used relative frontal alpha asymmetry (FAA), a method to measure functional lateralization of affective processing, to investigate psychobiological correlates of SFDs. With alpha activity being inversely related to cortical network activity, relative FAA refers to alpha activity on the right frontal lobe minus alpha activity on the left frontal lobe. Less relative left frontal activity, reflected by negative FAA scores, is associated with lower positive and greater negative affectivity, such as observed in depression. Due to its negative affective component (illness anxiety), we expected to find less relative left frontal activity pattern in SFDs, and positive associations with self-reported chronic stress and depression symptoms. We recorded resting-state EEG activity with 64 electrodes, placed in a 10-10 system in 26 patients with a primary SFD, 23 patients with a major depressive disorder and 25 healthy control participants. The groups did not differ in FAA. Nevertheless, across all participants, less relative left frontal activity was associated with chronic stress and depression symptoms. We concluded that FAA may not serve as an indicator of SFDs. As the relationship of FAA and depressive symptoms was fully mediated by chronic stress, future studies have to clarify whether the association between FAA and chronic stress may represent a shared underlying factor for the manifestation of mental health complaints, such as depression.

Mothers' and fathers' reflective functioning and its association with parenting behaviors and cortisol reactivity during a conflict interaction with their adolescent children.

We assessed parental reflective functioning (PRF) with the Parent Development Interview-Revised and investigated its association with parenting behaviors, that is, autonomy support and psychological control (operationalized in terms of behaviors promoting and undermining autonomy relatedness), and stress responses (cortisol reactivity) during a parent-child conflict interaction task (Family Interaction Task). Participants were 40 mothers and 28 fathers, who took part in the study together with their adolescent children (N = 49). Mothers had significantly lower PRF and displayed more psychologically controlling behaviors in the interaction with their children than fathers. Rather than sex per se, high levels of PRF were the best predictors of autonomy support, whereas lower levels of PRF predicted more psychological control. Higher levels of PRF were also the best predictor for lower levels of parenting stress. Stress in the context of parenting was neither related to autonomy support nor to psychological control, which were best predicted by divorced family status and, for psychological control only, by parental sex. The findings point to the potential utility of interventions aimed at improving PRF, especially in divorced families, given its protective effect on parenting behaviors and stress in the context of parenting. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Color-Encoded Links Improve Homophily Perception in Node-Link Diagrams.

Node-link diagrams enable visual assessment of homophily when viewers can identify and evaluate the relative number of intra-cluster and inter-cluster links. Our online experiment shows that a new design with link type encoded edge color leads to more accurate perception of homophily than a design with same-color edges.

Reduced concentration performance and heartbeat-evoked potential in individuals with a history of a SARS-CoV-2 infection.

The goal of characterizing long-term psychological and neural consequences of a SARS-CoV-2 infection has recently gained importance. Here, we examined the effect of a prior SARS-CoV-2 infection on neural markers of exteroceptive (P300) and interoceptive (heartbeat-evoked potential; HEP) signal processing, as well as on neuropsychological tests of attention, inhibition and episodic memory, in 23 adults with a self-reported history of SARS-CoV-2 infection versus 23 healthy controls. We found that the group with a prior infection showed decreased HEP (but not P300) amplitudes, as well as reduced attention/concentration performance. These results suggest that SARS-CoV-2 may damage neural structures of cardiac interoception, thereby potentially contributing to cognitive and psychological long-term deficits. Modulations of interoceptive processing after a SARS-CoV-2 infection are thus a promising target for future research.

The relationship between self-reported chronic stress, physiological stress axis dysregulation and medically-unexplained symptoms.

The positive feedback model of medically-unexplained symptoms posits that chronic stress affects the activity of the physiological stress axes, which in turn generates medically-unexplained symptoms. As a first step to empirically test its model assumptions, we investigated potential associations between chronic stress, physiological stress axis activity and medically-unexplained in a cross-sectional study. One hundred-ninety-nine healthy individuals provided self-reports on chronic stress and medically-unexplained symptoms, resting heart rate/variability (HR/HRV; e.g., root mean square of successive differences/RMSSD, low frequency/LF power), cortisol awakening response (CAR) and diurnal cortisol. Significant positive contributors to medically-unexplained symptoms were the chronic stress scales 'lack of social appreciation' and 'chronic worries', as well as CAR and LF HRV; diurnal cortisol was a negative contributor. Mediation analyses showed that the impact of neural indicators associated with physiological stress axis activity (HR/HRV) related to medically-unexplained symptoms, which was mediated by chronic stress, whereas the mediation effect as suggested by the positive feedback model was not significant. These cross-sectional findings do not support the positive feedback model. Longitudinal studies are required to conclude about potential mechanistic and causal relationships in the model. Nevertheless, our mediation analyses give first indication that the constitution of physiological stress axes may play a major role in how stressors are perceived and which kind of health-consequences (e.g., medically-unexplained symptoms) this may have.

Safety and performance assessment of hyaluronic acid-based vitreous substitutes in patients with phthisis bulbi.

PURPOSE: To assess the safety and performance of hyaluronic acid-based vitreous substitutes in phthitic eyes. METHODS: In this retrospective interventional study a total of 21 eyes from 21 patients with phthisis bulbi were treated at the Eye Clinic Sulzbach between August 2011 and June 2021. Patients who underwent a 23G pars plana vitrectomy received a vitreous substitute composed of (I) a non-crosslinked hyaluronic acid (Healon GV), (II) a crosslinked hyaluronic acid-based hydrogel (UVHA), or (III) silicone oil (SO-5000). Main outcome measures were the intraocular pressure (IOP), the visual acuity and the structural integrity of the retina and choroid assessed by optical coherence tomography. RESULTS: An increase in IOP ≥ 5 mmHg was achieved with SO-5000 in 5/8 eyes (6/10 interventions, 60.0%) for 36.4 ± 39.5 days, with Healon GV in 4/8 eyes (7/11 interventions, 63.6%) for 82.6 ± 92.5 days and with UVHA in 4/5 eyes (5/6 interventions, 83.3%) for 93.6 ± 92.5 days. Visual acuity increased in 5/21 eyes (23.8%), remained constant in 12/21 eyes (57.1%) and decreased in 4/21 eyes (19.0%). No enucleations were required during the mean follow-up time of 192 ± 182 days. The OCT images indicated the preservation of retinal structures, while choroidal folds were only diminished in UVHA eyes. CONCLUSIONS: Hyaluronic acid-based hydrogels are biocompatible vitreous substitutes in humans and can increase and stabilize IOP in patients with phthisis bulbi for about 3 months.