A novel pulsatile blood pump design for cardiothoracic surgery: Proof-of-concept in a mock circulation.

BACKGROUND: Pulsatile perfusion during extracorporeal circulation is a promising concept to improve perfusion of critical organs. Clinical benefits are limited by the amount of pulsatile energy provided by standard pumps. The present study investigated the properties of a novel positive displacement blood pump in a mock circulation. METHODS: The pump was attached to an aortic model with a human-like geometry and compliance as a pseudo patient. Hemodynamic data were recorded while the pump settings were adjusted systematically. RESULTS: Using a regular oxygenator, maximum flow was 2.6 L/min at a pressure of 27 mm Hg and a frequency (F) of 90 bpm. Pulse pressure (PP; 28.9 mm Hg) and surplus hemodynamic energy (SHE; 26.1% of mean arterial pressure) were highest at F = 40 bpm. Flow and pressure profiles appeared sinusoid. Using a low-resistance membrane ventilator to assess the impact of back pressure, maximum flow was 4.0 L/min at a pressure of 58.6 mm Hg and F = 40 bpm. At F = 40 bpm, PP was 58.7 mm Hg with an SHE of 33.4%. SHE decreased with increasing flow, heart rate, and systolic percentage but surpassed 10% with reasonable settings. CONCLUSIONS: The present prototype achieved sufficient flow and pressure ranges only in the presence of a low-resistance membrane ventilator. It delivered supraphysiologic levels of pulse pressure and SHE. Further modifications are planned to establish this concept for adult pulsatile perfusion.

Improving adult pulsatile minimal invasive extracorporeal circulation in a mock circulation.

BACKGROUND: Pulsatile extracorporeal circulation (ECC) may improve perfusion of critical organs during cardiac surgery. This study analyzed the influence of the components of a minimal invasive ECC (MiECC) on the transfer of pulsatile energy into the pseudo-patient of a mock circulation. METHODS: An aortic model with human-like geometry and compliance was perfused by a diagonal pump. Surplus hemodynamic energy (SHE) was determined from flow and pressure data. Five adult-size oxygenator models and three sizes of cannulas were compared. Pulsatile pump settings were optimized, and parallel dual-pump configurations were evaluated. RESULTS: Oxygenator models showed up to twofold differences in pressure gradients and influenced SHE at flow rates up to 2.0 L min-1 . Adjustments of frequency, systole duration, and rotational speed gain significantly improved SHE compared with empirical settings, with SHE above 21% of mean arterial pressure at flow rates of 1.0 L min-1 to 1.5 L min-1 and SHE above 5% at 3.5 L min-1 . Small diameter cannula (15 Fr) limited SHE compared with larger cannula (21 Fr and 23 Fr). Two diagonal pumps did not provide higher SHE than a single pump, but permitted additional control over pulse pressure and SHE by varying the total fraction of pulsatile flow and the fraction of flow bypassing the oxygenator. CONCLUSIONS: Proper selection of components and optimizations of pump settings significantly improved pulse pressure and SHE of pulsatile MiECC. Surplus hemodynamic energy depended on flow rate with a maximum at 1.0 L min-1 -1.5 L min-1 . Pulsatile MiECC may specifically assist organ perfusion during phases of low flow.

An Unprecedented Tolerance to Deletion of the Periplasmic Chaperones SurA, Skp, and DegP in the Nosocomial Pathogen Acinetobacter baumannii.

The outer membrane (OM) of Gram-negative bacteria efficiently protects from harmful environmental stresses such as antibiotics, disinfectants, or dryness. The main constituents of the OM are integral OM ß-barrel proteins (OMPs). In Gram-negative bacteria such as Escherichia coli, Yersinia enterocolitica, and Pseudomonas aeruginosa, the insertion of OMPs depends on a sophisticated biogenesis pathway. This comprises the SecYEG translocon, which enables inner membrane (IM) passage; the chaperones SurA, Skp, and DegP, which facilitate the passage of ß-barrel OMPs through the periplasm; and the ß-barrel assembly machinery (BAM), which facilitates insertion into the OM. In E. coli, Y. enterocolitica, and P. aeruginosa, the deletion of SurA is particularly detrimental and leads to a loss of OM integrity, sensitization to antibiotic treatment, and reduced virulence. In search of targets that could be exploited to develop compounds that interfere with OM integrity in Acinetobacter baumannii, we employed the multidrug-resistant strain AB5075 to generate single gene knockout strains lacking individual periplasmic chaperones. In contrast to E. coli, Y. enterocolitica, and P. aeruginosa, AB5075 tolerates the lack of SurA, Skp, or DegP with only weak mutant phenotypes. While the double knockout strains ΔsurAΔskp and ΔsurAΔdegP are conditionally lethal in E. coli, all double deletions were well tolerated by AB5075. Strikingly, even a triple-knockout strain of AB5075, lacking surA, skp, and degP, was viable. IMPORTANCE Acinetobacter baumannii is a major threat to human health due to its ability to persist in the hospital environment, resistance to antibiotic treatment, and ability to deploy multiple and redundant virulence factors. In a rising number of cases, infections with multidrug-resistant A. baumannii end up fatally, because all antibiotic treatment options fail. Thus, novel targets have to be identified and alternative therapeutics have to be developed. The knockout of periplasmic chaperones has previously proven to significantly reduce virulence and even break antibiotic resistance in other Gram-negative pathogens. Our study in A. baumannii demonstrates how variable the importance of the periplasmic chaperones SurA, Skp, and DegP can be and suggests the existence of mechanisms allowing A. baumannii to cope with the lack of the three periplasmic chaperones.

Corrigendum: A Disease Pathway Framework for Pain Point Identification and Elaboration of Product Requirements Across Patient Care Plan Using Innovation Think Tank Global Infrastructure.

[This corrects the article DOI: 10.3389/fpubh.2022.862384.].

[Physical therapy knowledge, skills, and competencies in the care of people with chronic pain]. / Physiotherapeutische Kenntnisse, Fertigkeiten und Kompetenzen in der Versorgung von Menschen mit chronischen Schmerzen.

BACKGROUND: Between 8 and 16 million people in Germany are affected by chronic pain, causing costs of up to 28.7 billion euros annually. Chronic pain is complex and has biopsychosocial aspects. Physiotherapeutic care requires special knowledge, skills and competencies. A publicly accessible description of these requirements does not currently exist in Germany. AIM: The aim of the work was to establish a consensus among experts working in Germany regarding the necessary knowledge, skills and competencies of physiotherapists in the care of people with chronic pain. METHODS: Two-stage Delphi procedure with 15 experts. In the first round of questions, knowledge, skills and competencies that had previously been identified in a systematic literature review were assessed and supplemented. In the second round of questions, the experts evaluated the additions made in the first round of questions with regard to their relevance. RESULTS: Of 219 evaluated statements, 124 were classified as absolutely relevant. In addition to anatomical and physiological pain knowledge, mainly educational and communication skills were rated as important. CONCLUSION: This overview may provide a basis for the development of a competency profile that can be used to develop contents for the modular design and standardisation of curricula in courses of study or training.

A Disease Pathway Framework for Pain Point Identification and Elaboration of Product Requirements Across Patient Care Plan Using Innovation Think Tank Global Infrastructure.

Healthcare providers as well as medical technologists lay a strong focus on clinical conditions for patient centric care delivery. Currently, the challenges are to (1) obtain a consolidated view of various stakeholders and pain points for the entire disease lifecycle, (2) identify interdependencies between different stages of the disease, and (3) prioritize solutions based on customer needs. A structured approach is required to address clinical needs across disease care plans tailored to different geographies and ethnicities. Innovation Think Tank (ITT) teams across multiple locations formed focus groups to elaborate the pathways of 22 global diseases, selected based on ranking of associated economic burden and threat to life. Ideation sessions were held to identify pain points and find innovative solutions. Additionally, inputs were taken from co-creation sessions at universities worldwide. The optimization and design of infographics and care plan was done based on the key information gathered-facts and figures, stakeholders, pain points and solutions. Finally, validation was obtained from clinical and technology experts globally. A disease pathway framework was created to develop pathways for 22 global diseases. Over 1,500 pain points were collected and about 1,900 ideas were proposed. The approach was applied to optimize its application to 30 product and portfolio definition projects over 2 years at Siemens Healthineers, as well as co-creation programs with universities and hospitals. The disease pathway framework provides a unique foundation for extensive collaboration among multiple stakeholders, through information sharing and delivering high-quality solutions based on the identified problems and customer needs.

Insights into visual working memory precision at the feature- and object-level from a hemispheric encoding manipulation.

Mnemonic precision is an important aspect of visual working memory (WM). Here, we probed mechanisms that affect precision for spatial (size) and non-spatial (colour) features of an object, and whether these features are encoded and/or stored separately in WM. We probed precision at the feature-level-that is, whether different features of a single object are represented separately or together in WM-and the object-level-that is, whether different features across a set of sequentially presented objects are represented in the same or different WM stores. By manipulating whether stimuli were encoded by the left and/or right hemisphere, we gained further insights into how objects are represented in WM. At the feature-level, we tested whether recall fidelity for the two features of an object fluctuated in tandem from trial to trial. We observed no significant coupling under either central or lateralized encoding, supporting the claim of parallel feature channels at encoding. At the level of WM storage of a set of objects, we found asymmetric feature interference under central encoding, whereby an increase in colour load led to a decrease in size precision. When objects were encoded by a single hemisphere, however, we found largely independent feature stores. Precision for size was more resistant to interference from the size of another object under right-hemisphere encoding; by contrast, precision for colour did not differ across hemispheres, suggesting a more distributed WM store. These findings suggest that distinct features of a single object are represented separately but are then partially integrated during maintenance of a set of sequentially presented objects.

Neurocognitive Development of the Resolution of Selective Visuo-Spatial Attention: Functional MRI Evidence From Object Tracking.

Our ability to select relevant information from the environment is limited by the resolution of attention - i.e., the minimum size of the region that can be selected. Neural mechanisms that underlie this limit and its development are not yet understood. Functional magnetic resonance imaging (fMRI) was performed during an object tracking task in 7- and 11-year-old children, and in young adults. Object tracking activated canonical fronto-parietal attention systems and motion-sensitive area MT in children as young as 7 years. Object tracking performance improved with age, together with stronger recruitment of parietal attention areas and a shift from low-level to higher-level visual areas. Increasing the required resolution of spatial attention - which was implemented by varying the distance between target and distractors in the object tracking task - led to activation increases in fronto-insular cortex, medial frontal cortex including anterior cingulate cortex (ACC) and supplementary motor area, superior colliculi, and thalamus. This core circuitry for attentional precision was recruited by all age groups, but ACC showed an age-related activation reduction. Our results suggest that age-related improvements in selective visual attention and in the resolution of attention are characterized by an increased use of more functionally specialized brain regions during the course of development.

Variability in the Precision of Children's Spatial Working Memory.

Cognitive modeling studies in adults have established that visual working memory (WM) capacity depends on the representational precision, as well as its variability from moment to moment. By contrast, visuospatial WM performance in children has been typically indexed by response accuracy-a binary measure that provides less information about precision with which items are stored. Here, we aimed at identifying whether and how children's WM performance depends on the spatial precision and its variability over time in real-world contexts. Using smartphones, 110 Grade 3 and Grade 4 students performed a spatial WM updating task three times a day in school and at home for four weeks. Measures of spatial precision (i.e., Euclidean distance between presented and reported location) were used for hierarchical modeling to estimate variability of spatial precision across different time scales. Results demonstrated considerable within-person variability in spatial precision across items within trials, from trial to trial and from occasion to occasion within days and from day to day. In particular, item-to-item variability was systematically increased with memory load and lowered with higher grade. Further, children with higher precision variability across items scored lower in measures of fluid intelligence. These findings emphasize the important role of transient changes in spatial precision for the development of WM.

Distributed patterns of occipito-parietal functional connectivity predict the precision of visual working memory.

Limitations in visual working memory (WM) quality (i.e., WM precision) may depend on perceptual and attentional limitations during stimulus encoding, thereby affecting WM capacity. WM encoding relies on the interaction between sensory processing systems and fronto-parietal 'control' regions, and differences in the quality of this interaction are a plausible source of individual differences in WM capacity. Accordingly, we hypothesized that the coupling between perceptual and attentional systems affects the quality of WM encoding. We combined fMRI connectivity analysis with behavioral modeling by fitting a variable precision and fixed capacity model to the performance data obtained while participants performed a visual delayed continuous response WM task. We quantified functional connectivity during WM encoding between occipital and parietal brain regions activated during both perception and WM encoding, as determined using a conjunction of two independent experiments. The multivariate pattern of voxel-wise inter-areal functional connectivity significantly predicted WM performance, most specifically the mean of WM precision but not the individual number of items that could be stored in memory. In particular, higher occipito-parietal connectivity was associated with higher behavioral mean precision. These results are consistent with a network perspective of WM capacity, suggesting that the efficiency of information flow between perceptual and attentional neural systems is a critical determinant of limitations in WM quality.

Superior Intraparietal Sulcus Controls the Variability of Visual Working Memory Precision.

UNLABELLED: Limitations of working memory (WM) capacity depend strongly on the cognitive resources that are available for maintaining WM contents in an activated state. Increasing the number of items to be maintained in WM was shown to reduce the precision of WM and to increase the variability of WM precision over time. Although WM precision was recently associated with neural codes particularly in early sensory cortex, we have so far no understanding of the neural bases underlying the variability of WM precision, and how WM precision is preserved under high load. To fill this gap, we combined human fMRI with computational modeling of behavioral performance in a delayed color-estimation WM task. Behavioral results replicate a reduction of WM precision and an increase of precision variability under high loads (5 > 3 > 1 colors). Load-dependent BOLD signals in primary visual cortex (V1) and superior intraparietal sulcus (IPS), measured during the WM task at 2-4 s after sample onset, were modulated by individual differences in load-related changes in the variability of WM precision. Although stronger load-related BOLD increase in superior IPS was related to lower increases in precision variability, thus stabilizing WM performance, the reverse was observed for V1. Finally, the detrimental effect of load on behavioral precision and precision variability was accompanied by a load-related decline in the accuracy of decoding the memory stimuli (colors) from left superior IPS. We suggest that the superior IPS may contribute to stabilizing visual WM performance by reducing the variability of memory precision in the face of higher load. SIGNIFICANCE STATEMENT: This study investigates the neural bases of capacity limitations in visual working memory by combining fMRI with cognitive modeling of behavioral performance, in human participants. It provides evidence that the superior intraparietal sulcus (IPS) is a critical brain region that influences the variability of visual working memory precision between and within individuals (Fougnie et al., 2012; van den Berg et al., 2012) under increased memory load, possibly in cooperation with perceptual systems of the occipital cortex. These findings substantially extend our understanding of the nature of capacity limitations in visual working memory and their neural bases. Our work underlines the importance of integrating cognitive modeling with univariate and multivariate methods in fMRI research, thus improving our knowledge of brain-behavior relationships.

Loss of LDOC1 expression by promoter methylation in cervical cancer cells.

Cervical cancer lacks reliable prognostic factors for both progression and chemotherapeutic responsiveness. The expression of the LDOC1 tumor suppressor candidate was therefore investigated. In four of six cervical cancer cell lines tested, expression of LDOC1 was silenced. Downregulation of LDOC1 could also be shown in biopsies of cervical cancer specimens. PCR-based promoter methylation analysis revealed a significant association between promoter methylation and the loss of LDOC1 expression, which could be reverted by DNA methyltransferase inhibitors. This indicates that silencing of LDOC1 is a frequent event in cervical cancer and may be of interest as a molecular marker in cervical cancer.

Analysis of the relationship between the inner structure and the magnitude of atherosclerotic plaques.

The aim of this study was ultrasound evaluation of atherosclerotic plaque morphology in relation to the degree of coronary artery lumen narrowing in patients with ischaemic heart disease. Intravascular ultrasound was performed on 38 patients (30 men and 8 women) aged 35 to 77 (average age 60 +/- 11 years old) with symptoms of ischaemic heart disease. The structure of atherosclerotic plaques with a degree of lumen narrowing of < 50% (1st group) was distinctly different from the structure of plaques with a degree of lumen narrowing of 50-75% (2nd group, p = 0.0045) and the structure of plaques with a degree of lumen narrowing of >/= 75% (3rd group, p < 0.001). The incidence of soft plaques decreased, whereas the percentage of mixed and hard plaques increased gradually with the increase in the degree of artery lumen narrowing. Significant differences in the incidence of plaque calcification were observed between the groups evaluated with crosssections of different degrees of lumen narrowing (p = 0.0032). The smallest number of calcifications was discovered in the 1st group as compared to the 2nd (p = 0.0027) and the 3rd group (p = 0.0026). With a higher degree of lumen narrowing, a lower percentage of eccentric plaques and a higher percentage of concentric plaques were observed. There were more eccentric plaques and fewer concentric plaques in cross-sections of the 1 st group as compared to the 2nd group (p = 0.0056) and the 3rd group (p = 0.0018). A comparison between the 2nd and 3rd groups showed no significant difference in the incidence of eccentric or concentric plaques (p = 0.5). In conclusion, intravascular ultrasound evaluation revealed significant relationships between the structure, presence of calcifications and location of atherosclerotic plaques and the degree of artery lumen narrowing. The incidence of mixed, hard, calcified and concentric plaques increased, whereas the percentage of soft, non-calcified and eccentric plaques decreased gradually with the increase in the degree of artery lumen narrowing.