Pacing therapy for atrioventricular dromotropathy: A combined computational-experimental-clinical study

AIMS: Investigate haemodynamic effects, and their mechanisms, of restoring atrioventricular (AV)-coupling using pacemaker therapy in normal and failing hearts in a combined computational-experimental-clinical study. METHODS AND RESULTS: Computer simulations were performed in the CircAdapt model of the normal and failing human heart and circulation. Experiments were performed in a porcine model of AV dromotropathy. In a proof-of-principle clinical study, left ventricular (LV) pressure and volume were measured in 22 heart failure (HF) patients (LV ejection fraction \u3c35%) with prolonged PR interval (\u3e230 ms) and narrow or non-left bundle branch block QRS complex. Computer simulations and animal studies in normal hearts showed that restoring of AV-coupling with unchanged ventricular activation sequence significantly increased LV filling, mean arterial pressure, and cardiac output by 10-15%. In computer simulations of failing hearts and in HF patients, reducing PR interval by biventricular (BiV) pacing (patients: from 300 ± 61 to 137 ± 30 ms) resulted in significant increases in LV stroke volume and stroke work (patients: 34 ± 40% and 26 ± 31%, respectively). However, worsening of ventricular dyssynchrony by using right ventricular (RV) pacing abrogated the benefit of restoring AV-coupling. In model simulations, animals and patients, the increase of LV filling and associated improvement of LV pump function coincided with both larger mitral inflow (E- and A-wave area) and reduction of diastolic mitral regurgitation. CONCLUSION: Restoration of AV-coupling by BiV pacing in normal and failing hearts with prolonged AV conduction leads to considerable haemodynamic improvement. These results indicate that BiV or physiological pacing, but not RV pacing, may improve cardiac function in patients with HF and prolonged PR interval

Personal characteristics of World War Two survivor offspring related to the presence of indirect intrusions

Background: A substantial proportion of clinical World War Two survivor offspring reports intrusions about war events they did not experience themselves. Objective: To help identify factors that contribute to the development of such indirect intrusions (i.e. intrusions about non-self-experienced traumatic events), we examined the personal characteristics of survivor offspring that were related to the presence of indirect intrusions. To explore the specificity of these relationships, we compared characteristics related to the presence of indirect and direct intrusions (i.e. intrusions about self-experienced traumatic events). Methods: Participants (N = 98) were post-war offspring of World War Two survivors in treatment in one of two clinics specialized in mental health services for war victims. We assessed the presence of indirect and direct intrusions as well as the following personal characteristics: gender, education level, trait dissociation, affect intensity, attentional control, mental imagery, fantasy proneness, and current psychopathology. Results: Reports of indirect intrusions were more frequent in individuals high in fantasy proneness, trait dissociation, and current psychopathology. Reports of direct intrusions were more frequent in women, individuals scoring high on trait dissociation, affect intensity, and current psychopathology. Fantasy proneness was a unique correlate of indirect intrusions. Conclusions: These findings are consistent with the idea that intrusions are the result of (re)constructive processes affected by several factors including personal characteristics. HIGHLIGHTS Offspring of World War Two survivors often experience indirect intrusions. We examined personal characteristics related to indirect and direct intrusions. Fantasy proneness was the best predictor of indirect intrusions. Gender was the best predictor of direct intrusions

The link between dissociative tendencies and hyperassociativity

Background and objectives: Anecdotal and research evidence suggests that individuals with dissociative symptoms exhibit hyperassociativity, which might explain several key features of their condition. The aim of our study was to investigate the link between dissociative tendencies and hyperassociativity among college students. Methods: The study (n = 118) entailed various measures of hyperassociativity, measures of dissociative tendencies, depressive experiences, unusual sleep experiences, cognitive failures, and alexithymia. Results: We found a positive association between dissociative experiences (i.e., depersonalization) and hyperassociativity specific for associative fluency and associative flexibility tasks (including neutral and valenced material), but not for a remote association task. We also found tentative evidence for cognitive failures and alexithymia explaining the link between hyperassociativity and daytime dissociation and nighttime unusual sleep experiences. Limitations: Limitations include the use of hyperassociation tasks limited to verbal associations vs. imagistic associations, the lack of a measure of trauma history, and a sample limited to college students. Conclusion: Our study reports a link between depersonalization and hyperassociativity on tasks that allow for free associations across different semantic domains, potentially explained by alexithymia and cognitive failures. This finding may, with replication, open the pathway to applied intervention studies

Summary data of potency and parameter information from semi-mechanistic PKPD modeling of prolactin release following administration of the dopamine D2 receptor antagonists risperidone, paliperidone and remoxipride in rats

We provide the reader with relevant data related to our recently published paper, comparing two mathematical models to describe prolactin turnover in rats following one or two doses of the dopamine D2 receptor antagonists risperidone, paliperidone and remoxipride, “A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D2 receptor antagonists in rats” (Taneja et al., 2016) [1]. All information is tabulated. Summary level data on the in vitro potencies and the physicochemical properties is presented in Table 1. Model parameters required to explore the precursor pool model are presented in Table 2. In Table 3, estimated parameter comparisons for both models are presented, when separate potencies are estimated for risperidone and paliperidone, as compared to a common potency for both drugs. In Table 4, parameter estimates are compared when the drug effect is parameterized in terms of drug concentration or receptor occupancy

Cross-Comparison of Climate Change adaptation Strategies Across Large River Basins in Europe, Africa and Asia

A cross-comparison of climate change adaptation strategies across regions was performed, considering six large river basins as case study areas. Three of the basins, namely the Elbe, Guadiana, and Rhine, are located in Europe, the Nile Equatorial Lakes region and the Orange basin are in Africa, and the Amudarya basin is in Central Asia. The evaluation was based mainly on the opinions of policy makers and water management experts in the river basins. The adaptation strategies were evaluated considering the following issues: expected climate change, expected climate change impacts, drivers for development of adaptation strategy, barriers for adaptation, state of the implementation of a range of water management measures, and status of adaptation strategy implementation. The analysis of responses and cross-comparison were performed with rating the responses where possible. According to the expert opinions, there is an understanding in all six regions that climate change is happening. Different climate change impacts are expected in the basins, whereas decreasing annual water availability, and increasing frequency and intensity of droughts (and to a lesser extent floods) are expected in all of them. According to the responses, the two most important drivers for development of adaptation strategy are: climate-related disasters, and national and international policies. The following most important barriers for adaptation to climate change were identified by responders: spatial and temporal uncertainties in climate projections, lack of adequate financial resources, and lack of horizontal cooperation. The evaluated water resources management measures are on a relatively high level in the Elbe and Rhine basins, followed by the Orange and Guadiana. It is lower in the Amudarya basin, and the lowest in the NEL region, where many measures are only at the planning stage. Regarding the level of adaptation strategy implementation, it can be concluded that the adaptation to climate change has started in all basins, but progresses rather slowl

Time spent outdoors as an intervention for myopia prevention and control in children: an overview of systematic reviews

Purpose: Outdoor light exposure is considered a safe and effective strategy to reduce myopia development and aligns with existing public health initiatives to promote healthier lifestyles in children. However, it is unclear whether this strategy reduces myopia progression in eyes that are already myopic. This study aims to conduct an overview of systematic reviews (SRs) reporting time spent outdoors as a strategy to prevent myopia or slow its progression in children. Methods: We searched the Cochrane Library, EMBASE, MEDLINE and CINAHL from inception to 1 November 2020 to identify SRs that evaluated the association between outdoor light exposure and myopia development or progression in children. Outcomes included incident myopia, prevalent myopia and change in spherical equivalent refractive error (SER) and axial length (AL) to evaluate annual rates of myopia progression. The methodological quality and risk of bias of included SRs were assessed using the AMSTAR-2 and ROBIS tools, respectively. Results: Seven SRs were identified, which included data from 47 primary studies with 63,920 participants. Pooled estimates (risk or odds ratios) consistently demonstrated that time outdoors was associated with a reduction in prevalence and incidence of myopia. In terms of slowing progression in eyes that were already myopic, the reported annual reductions in SER and AL from baseline were small (0.13–0.17 D) and regarded as clinically insignificant. Methodological quality assessment using AMSTAR-2 found that all reviews had one or more critical flaws and the ROBIS tool identified a low risk of bias in only two of the included SRs. Conclusion: This overview found that increased exposure to outdoor light reduces myopia development. However, based on annual change in SER and AL, there is insufficient evidence for a clinically significant effect on myopia progression. The poor methodological quality and inconsistent reporting of the included systematic reviews reduce confidence in the estimates of effect

Personal characteristics of World War Two survivor offspring related to the presence of indirect intrusions

Background: A substantial proportion of clinical World War Two survivor offspring reports intrusions about war events they did not experience themselves. Objective: To help identify factors that contribute to the development of such indirect intrusions (i.e. intrusions about non-self-experienced traumatic events), we examined the personal characteristics of survivor offspring that were related to the presence of indirect intrusions. To explore the specificity of these relationships, we compared characteristics related to the presence of indirect and direct intrusions (i.e. intrusions about self-experienced traumatic events). Methods: Participants (N = 98) were post-war offspring of World War Two survivors in treatment in one of two clinics specialized in mental health services for war victims. We assessed the presence of indirect and direct intrusions as well as the following personal characteristics: gender, education level, trait dissociation, affect intensity, attentional control, mental imagery, fantasy proneness, and current psychopathology. Results: Reports of indirect intrusions were more frequent in individuals high in fantasy proneness, trait dissociation, and current psychopathology. Reports of direct intrusions were more frequent in women, individuals scoring high on trait dissociation, affect intensity, and current psychopathology. Fantasy proneness was a unique correlate of indirect intrusions. Conclusions: These findings are consistent with the idea that intrusions are the result of (re)constructive processes affected by several factors including personal characteristics. HIGHLIGHTS: Offspring of World War Two survivors often experience indirect intrusions. We examined personal characteristics related to indirect and direct intrusions. Fantasy proneness was the best predictor of indirect intrusions. Gender was the best predictor of direct intrusions

Capture the fracture: a best practice framework and global campaign to break the fragility fracture cycle

Summary The International Osteoporosis Foundation (IOF) Capture the Fracture Campaign aims to support implementation of Fracture Liaison Services (FLS) throughout the world. Introduction FLS have been shown to close the ubiquitous secondary fracture prevention care gap, ensuring that fragility fracture sufferers receive appropriate assessment and intervention to reduce future fracture risk. Methods Capture the Fracture has developed internationally endorsed standards for best practice, will facilitate change at the national level to drive adoption of FLS and increase awareness of the challenges and opportunities presented by secondary fracture prevention to key stakeholders. The Best Practice Framework (BPF) sets an international benchmark for FLS, which defines essential and aspirational elements of service delivery. Results The BPF has been reviewed by leading experts from many countries and subject to beta-testing to ensure that it is internationally relevant and fit-for-purpose. The BPF will also serve as a measurement tool for IOF to award ‘Capture the Fracture Best Practice Recognition’ to celebrate successful FLS worldwide and drive service development in areas of unmet need. The Capture the Fracture website will provide a suite of resources related to FLS and secondary fracture prevention, which will be updated as new materials become available. A mentoring programme will enable those in the early stages of development of FLS to learn from colleagues elsewhere that have achieved Best Practice Recognition. A grant programme is in development to aid clinical systems which require financial assistance to establish FLS in their localities. Conclusion Nearly half a billion people will reach retirement age during the next 20 years. IOF has developed Capture the Fracture because this is the single most important thing that can be done to directly improve patient care, of both women and men, and reduce the spiralling fracture-related care costs worldwide.</p

Fact or Factitious? A Psychobiological Study of Authentic and Simulated Dissociative Identity States

BACKGROUND: Dissociative identity disorder (DID) is a disputed psychiatric disorder. Research findings and clinical observations suggest that DID involves an authentic mental disorder related to factors such as traumatization and disrupted attachment. A competing view indicates that DID is due to fantasy proneness, suggestibility, suggestion, and role-playing. Here we examine whether dissociative identity state-dependent psychobiological features in DID can be induced in high or low fantasy prone individuals by instructed and motivated role-playing, and suggestion. METHODOLOGY/PRINCIPAL FINDINGS: DID patients, high fantasy prone and low fantasy prone controls were studied in two different types of identity states (neutral and trauma-related) in an autobiographical memory script-driven (neutral or trauma-related) imagery paradigm. The controls were instructed to enact the two DID identity states. Twenty-nine subjects participated in the study: 11 patients with DID, 10 high fantasy prone DID simulating controls, and 8 low fantasy prone DID simulating controls. Autonomic and subjective reactions were obtained. Differences in psychophysiological and neural activation patterns were found between the DID patients and both high and low fantasy prone controls. That is, the identity states in DID were not convincingly enacted by DID simulating controls. Thus, important differences regarding regional cerebral bloodflow and psychophysiological responses for different types of identity states in patients with DID were upheld after controlling for DID simulation. CONCLUSIONS/SIGNIFICANCE: The findings are at odds with the idea that differences among different types of dissociative identity states in DID can be explained by high fantasy proneness, motivated role-enactment, and suggestion. They indicate that DID does not have a sociocultural (e.g., iatrogenic) origin