Marine Sponge-Derived Secondary Metabolites Modulate SARS-CoV-2 Entry Mechanisms.

The emergence of SARS-CoV 2 caused the COVID-19 pandemic, resulting in numerous global infections and deaths. In particular, people with metabolic diseases display an increased risk of severe COVID 19 and a fatal outcome. Treatment options for severe cases are limited, and the appearance of new virus variants complicates the development of novel therapies. To better manage viral infections like COVID 19, new therapeutic approaches are needed. Marine sponges offer a natural and renewable source of unique bioactive agents. These sponges produce secondary metabolites with various effects, including anti-viral, anti-inflammatory, and anti-tumorigenic properties. In the current study, we investigated the effect of five different marine sponge-derived secondary metabolites (four bromotyrosines and one sesquiterpenoid hydroquinone). Two of these, Avarol and Acetyl-dibromoverongiaquinol reduced the expression of ACE2, the main receptor for SARS-CoV 2, and the alternative receptor NRP1. Moreover, these substances derived from sponges demonstrated the ability to diminish the virus titer in SARS-CoV 2-infected cells, especially concerning the Omicron lineage. However, the reduction was not substantial enough to expect a significant impact on infected humans. Consequently, the investigated sponge-derived secondary metabolites are not likely to be effective to treat COVID 19 as a stand-alone therapy.

[Experiences of uncertainty about the future, poverty risks, and precarious living situations in nursing homes]. / Erleben von Zukunftsunsicherheit, Armutsrisiken und prekären Lebenslagen im Pflegeheim.

The living situation of people in nursing homes, with a specific vulnerability to care-related impoverishment, is underresearched. This article deals with experiences of uncertainty, poverty and a precarious life situation of care home residents in later life. The data basis is supplied by an ethnographic study of ageing and living with chronic health conditions. A range of precarious living situations are outlined on the basis of real cases. Insights gleaned include: people with diverse sociobiographical backgrounds can be affected by insecurity, poverty and precarious life situations as a result of becoming dependent on help and the transition to care homes. Not knowing whether available funds will suffice to cover rising costs until the end of life is a common form of uncertainty about the future. The threat of poverty or becoming dependent on state benefits can exacerbate experiences of loss associated with institutional care, losing autonomy, opportunities for participation, and options for shaping one's life and can further destabilize the overall condition. This anguish remains largely invisible; structural problems are individualized.

Efficient production of inhibitor-free foamy virus glycoprotein-containing retroviral vectors by proteoglycan-deficient packaging cells.

Foamy viruses (FVs) or heterologous retroviruses pseudotyped with FV glycoprotein enable transduction of a great variety of target tissues of disparate species. Specific cellular entry receptors responsible for this exceptionally broad tropism await their identification. Though, ubiquitously expressed heparan sulfate proteoglycan (HS-PG) is known to serve as an attachment factor of FV envelope (Env)-containing virus particles, greatly enhancing target cell permissiveness. Production of high-titer, FV Env-containing retroviral vectors is strongly dependent on the use of cationic polymer-based transfection reagents like polyethyleneimine (PEI). We identified packaging cell-surface HS-PG expression to be responsible for this requirement. Efficient release of FV Env-containing virus particles necessitates neutralization of HS-PG binding sites by PEI. Remarkably, remnants of PEI in FV Env-containing vector supernatants, which are not easily removable, negatively impact target cell transduction, in particular those of myeloid and lymphoid origin. To overcome this limitation for production of FV Env-containing retrovirus supernatants, we generated 293T-based packaging cell lines devoid of HS-PG by genome engineering. This enabled, for the first, time production of inhibitor-free, high-titer FV Env-containing virus supernatants by non-cationic polymer-mediated transfection. Depending on the type of virus, produced titers were 2- to 10-fold higher compared with those obtained by PEI transfection.

Positive Psychological Coaching Tools and Techniques: A Systematic Review and Classification.

Positive psychological coaching (PPC) has emerged as a popular "paradigm" for practitioners interested in the professional development of people. A recent review consolidated the literature on PPC and produced a 5-phase positive psychological coaching model aimed at facilitating professional growth. However, little is known about practically operationalizing each phase of the coaching process (i.e., how to facilitate each phase and which underlying tools and techniques could be employed to do so). As such, the purpose of this systematic review was to address this limitation by (a) determining which coaching tools and techniques are proposed within the coaching literature and (b) classifying the identified tools and techniques into the respective phases of PPC model. The investigation used a two-step approach by conducting a systematic literature review (to identify various PPC tools/techniques) followed by an iterative heuristic classification process (to assign these PPC tools/techniques to a known PPC model). The systematic literature review resulted in 24 peer-reviewed publications on positive psychological coaching, providing 117 different coaching tools that could be condensed into 18 overarching coaching techniques. The iterative classification process showed that most techniques and tools are useful in at least two phases. Interestingly, experts still vary in opinion on the timing and application of these specific techniques and tools within the positive psychological coaching process. This study provides researchers and practitioners with practical guidelines to facilitate a positive psychological coaching process.

Viral infiltration of pancreatic islets in patients with COVID-19.

Metabolic diseases are associated with an increased risk of severe COVID-19 and conversely, new-onset hyperglycemia and complications of preexisting diabetes have been observed in COVID-19 patients. Here, we performed a comprehensive analysis of pancreatic autopsy tissue from COVID-19 patients using immunofluorescence, immunohistochemistry, RNA scope and electron microscopy and detected SARS-CoV-2 viral infiltration of beta-cells in all patients. Using SARS-CoV-2 pseudoviruses, we confirmed that isolated human islet cells are permissive to infection. In eleven COVID-19 patients, we examined the expression of ACE2, TMPRSS and other receptors and factors, such as DPP4, HMBG1 and NRP1, that might facilitate virus entry. Whereas 70% of the COVID-19 patients expressed ACE2 in the vasculature, only 30% displayed ACE2-expression in beta-cells. Even in the absence of manifest new-onset diabetes, necroptotic cell death, immune cell infiltration and SARS-CoV-2 viral infection of pancreatic beta-cells may contribute to varying degrees of metabolic dysregulation in patients with COVID-19.

Identification of an Intermediate Step in Foamy Virus Fusion.

Viral glycoprotein-mediated membrane fusion is an essential step for productive infection of host cells by enveloped viruses; however, due to its rarity and challenges in detection, little is known about the details of fusion events at the single particle level. Here, we have developed dual-color foamy viruses (FVs) composed of eGFP-tagged prototype FV (PFV) Gag and mCherry-tagged Env of either PFV or macaque simian FV (SFVmac) origin that have been optimized for detection of the fusion process. Using our recently developed tracking imaging correlation (TrIC) analysis, we were able to detect the fusion process for both PFV and SFVmac Env containing virions. PFV Env-mediated fusion was observed both at the plasma membrane as well as from endosomes, whereas SFVmac Env-mediated fusion was only observed from endosomes. PFV Env-mediated fusion was observed to happen more often and more rapidly than as for SFVmac Env. Strikingly, using the TrIC method, we detected a novel intermediate state where the envelope and capsids are still tethered but separated by up to 400 nm before final separation of Env and Gag occurred.

Positive Psychological Coaching Definitions and Models: A Systematic Literature Review.

Despite the popularity of the term Positive Psychological Coaching within the literature, there is no consensus as to how it should be defined (framed) or what the components of a positive coaching "model" should include. The aim of this systematic review was to define positive psychological coaching and to construct a clear demarcated positive psychological coaching model based on the literature. A systematic literature review led to the extraction of 2,252 records. All records were screened using specific inclusion/exclusion criteria, which resulted in the exclusion of records based on duplicates (n = 1,232), titles (n = 895), abstracts (n = 78), and criteria violations (n = 23). Twenty-four academic, peer-reviewed publications on positive psychological coaching were included. Data relating to conceptual definitions and coaching models/phases/frameworks were extracted and processed through thematic content analysis. Our results indicate that positive psychological coaching can be defined as a short to medium term professional, collaborative relationship between a client and coach, aimed at the identification, utilization, optimization, and development of personal strengths and resources in order to enhance positive states, traits and behaviors. Utilizing Socratic goal setting and positive psychological evidence-based approaches to facilitate personal growth, optimal functioning, enhanced wellbeing, and the actualization of people's potential. Further, eight critical components of a positive psychological coaching model were identified and discussed. The definition and coaching process identified in this study will provide coaches with a fundamental positive psychological framework for optimizing people's potential.

Comparison of the therapeutic efficacy of salicylic acid paste with a polyurethane wound dressing for the treatment of digital dermatitis lesions in dairy cows.

There is little evidence of the efficacy of artificial polymers for controlling bovine digital dermatitis (BDD) as a major problem of intensive dairy productions worldwide. We therefore aimed to compare salicylic acid (SA)-based paste with a polyurethane (PU) wound dressing on a German Holstein dairy farm over a maximum 56-d period. On d 0, 109 ft with active BDD lesions from 109 cows were randomly assigned to two treatment groups: (1) SA group received a topical SA-containing paste and (2) PU group was treated with a PU wound dressing. Dressing changes were performed according to manufacturer's instructions until clinical cure (transition from active M1 or M2 to non-active M4 or healed M0 stages), whereby a clinical scoring of lesions was additionally conducted. Data from 100 ft could be analyzed (nSA = 54; nPU = 46). There was a significant reduction of the lesion score over time within each group (SA: d 0-d 14; PU: d 0-d 28, p < .05). Score differences between first (d 0) and second (SA: d 7; PU: d 14) as well as between first and third (SA: d 14; PU: d 28) evaluation did not differ significantly (p > .05). The proportion of clinically cured cows was higher in SA than in PU on d 14 (96.3 vs. 32.6%) as well as on d 28 (100 vs. 54.3%) after initial treatment (p < .05). Analysis of survival to cure in a Cox regression model showed that hazard ratio (HR) was higher for SA with PU as baseline (HR: 6.324, 95% CI: 3.625-11.033, p < .05). However, while BDD scores at enrollment did not differ between treatments (p > .05), PU had a significantly lower final BDD score (p < .05). In conclusion, evidence on the efficacy of PU bandages to treat BDD lesions is provided and further studies on bacteriological cure as well as recurrence rates are needed.

[The Development of Social Innovations in Health Care and the Role of Science and Research]. / Die Entwicklung Sozialer Innovationen in der Gesundheitsversorgung und die Rolle von Wissenschaft und Forschung.

In the course of demographic, epidemiological and social changes, various challenges arise concerning the organization of health care and health promotion for the population. Innovative approaches are needed to face these challenges. The focus in the theoretical work is on the analysis of the development of social innovations and on the role of science and research to solve social problems. First of all, the notion of innovation based on technologies will be expanded by social innovations. 2 approaches to promote social innovations are discussed: the systematic discovery and development of solutions in practice as well as the co-productive development in the terms of transdisciplinary research. It will be demonstrated that a cooperative and co-productive research and development process brings new requirements regarding scientific practice so that a discussion about the organisation and general conditions of transdisciplinary research and development in the health (service) research has to be strengthened.

Yoga Training in Junior Primary School-Aged Children Has an Impact on Physical Self-Perceptions and Problem-Related Behavior.

The present pilot study investigated the effects of yoga training, as compared to physical skill training, on motor and executive function, physical self-concept, and anxiety-related behavior in junior primary school-aged children. Twenty-four participants with a mean age of 8.4 (±1.4) years completed either yoga or physical skill training twice a week for 6 weeks outside of regular school class time. Both forms of training were delivered in an individualized and child-oriented manner. The type of training did not result in any significant differences in movement and executive function outcomes. In terms of physical self-concept, significant group differences were revealed only for perceived movement speed such that yoga training resulted in perceptions of being slower while physical skill training resulted in perceptions of moving faster. Analysis of anxiety related outcomes revealed significant group effects only for avoidance behavior and coping strategies. Avoidance behavior increased following yoga training, but decreased following physical skill training. In addition, following yoga training, children showed an increased use of divergent coping strategies when facing problematic situations while after physical skill training children demonstrated a decrease in use of divergent coping strategies. Changes in overall physical self-concept scores were not significantly correlated with changes in avoidance behavior following yoga training. In contrast, following physical skill training increased physical self-concept was significantly correlated with decreases in avoidance behavior. In sum, exposure to yoga or physical skill training appears to result in distinct effects for specific domains of physical self-concept and anxiety-related behavior. Further studies with larger samples and more rigorous methodologies are required to further investigate the effects reported here. With respect to future studies, we address potential research questions and specific features associated with the investigation of the effects of yoga in a sample of school-aged children.

Integrated Care for People with Dementia-Results of a Social-Scientific Evaluation of an Established Dementia Care Model.

Currently, approximately 46.8 million people worldwide and 1.47 million German people are affected by dementia. The rising numbers of cases of people with dementia, the need for complex care and the insufficient care available call for innovative and sustainable solutions both in Germany and many other countries. This article presents results of the social-scientific evaluation of an established care model for people with dementia developed by the professionals as a result of acute problems in care in north-east Germany. In addition to the central elements of the model, the conditions of intersectoral and interprofessional cooperation as well as the qualification profile requirements of the professional groups involved are presented in detail. The results can give suggestions for the organization of integrated care for people with dementia in other countries. Further, the author would hereby like to highlight the gain from the scientific examination of solutions to problems in the field.

Plasmodium berghei MAPK1 displays differential and dynamic subcellular localizations during liver stage development.

Mitogen-activated protein kinases (MAPKs) regulate key signaling events in eukaryotic cells. In the genomes of protozoan Plasmodium parasites, the causative agents of malaria, two genes encoding kinases with significant homology to other eukaryotic MAPKs have been identified (mapk1, mapk2). In this work, we show that both genes are transcribed during Plasmodium berghei liver stage development, and analyze expression and subcellular localization of the PbMAPK1 protein in liver stage parasites. Live cell imaging of transgenic parasites expressing GFP-tagged PbMAPK1 revealed a nuclear localization of PbMAPK1 in the early schizont stage mediated by nuclear localization signals in the C-terminal domain. In contrast, a distinct localization of PbMAPK1 in comma/ring-shaped structures in proximity to the parasite's nuclei and the invaginating parasite membrane was observed during the cytomere stage of parasite development as well as in immature blood stage schizonts. The PbMAPK1 localization was found to be independent of integrity of a motif putatively involved in ATP binding, integrity of the putative activation motif and the presence of a predicted coiled-coil domain in the C-terminal domain. Although PbMAPK1 knock out parasites showed normal liver stage development, the kinase may still fulfill a dual function in both schizogony and merogony of liver stage parasites regulated by its dynamic and stage-dependent subcellular localization.

Periodontitis is related to lung volumes and airflow limitation: a cross-sectional study.

This study aimed to assess the potential association of periodontal diseases with lung volumes and airflow limitation in a general adult population. Based on a representative population sample of the Study of Health in Pomerania (SHIP), 1463 subjects aged 25-86 years were included. Periodontal status was assessed by clinical attachment loss (CAL), probing depth and number of missing teeth. Lung function was measured using spirometry, body plethysmography and diffusing capacity of the lung for carbon monoxide. Linear regression models using fractional polynomials were used to assess associations between periodontal disease and lung function. Fibrinogen and high-sensitivity C-reactive protein (hs-CRP) were evaluated as potential intermediate factors. After full adjustment for potential confounders mean CAL was significantly associated with variables of mobile dynamic and static lung volumes, airflow limitation and hyperinflation (p<0.05). Including fibrinogen and hs-CRP did not change coefficients of mean CAL; associations remained statistically significant. Mean CAL was not associated with total lung capacity and diffusing capacity of the lung for carbon monoxide. Associations were confirmed for mean probing depth, extent measures of CAL/probing depth and number of missing teeth. Periodontal disease was significantly associated with reduced lung volumes and airflow limitation in this general adult population sample. Systemic inflammation did not provide a mechanism linking both diseases.

Deregulated ephrin-B2 signaling in mammary epithelial cells alters the stem cell compartment and interferes with the epithelial differentiation pathway.

Cancer most probably originates from stem/progenitor cells and exhibits a similar cell hierarchy as normal tissues. Moreover, there is growing evidence that only the stem cells are capable of metastasis formation. We have previously shown that overexpression of a dominant negative ephrin-B2 mutant interferes with mammary gland differentiation and confers a metastatic phenotype to NeuT-induced mammary tumors with an increase in cells with stem/progenitor characteristics. To investigate the role of ephrin-B2 in the control of the mammary stem cell niche, we analyzed the mammary stem and progenitor cell populations in transgenic mice overexpressing the mutant ephrin-B2. Quantification by FACS analysis revealed a significant increase of cells in the basal/alveolar cell-, the bi-potent progenitor- and the stem cell-enriched fractions. Moreover, the supposed precursors of estrogen receptor-positive cells were elevated in the stem cell-enriched fraction. In contrast, the epithelium from transgenic mice overexpressing the native ephrin-B2 gene showed an augmentation of the luminal cell- and the bi-potent progenitor-enriched fractions. Repopulation assays revealed that the epithelial cells of truncated ephrin-B2 transgenic epithelial cells have a higher regeneration capacity than those of controls and of native ephrin-B2 transgenic mice, confirming the augmentation of stem cells. Morphologically, these outgrowths exhibited impaired basal/luminal compartmentalization and epithelial polarization. These results demonstrate that deregulated ephrin-B2 expression interferes with the regulation of the stem cell niche and leads to a shift of the differentiation pathway and may thereby contribute to the acquisition of the metastatic phenotype long before carcinogenic growth becomes apparent.

Movement orientation is related to mental rotation in childhood.

The present study asked whether the ability to mentally rotate animal pictures was associated with orientation errors of aiming movements in 7- to 10-year-old children and adults. Mental rotation involves a mental change of the encoded picture's orientation, and one has to determine movement vector orientation in motor programming. In the children, slower rotations were related to higher absolute orientation errors, and less correct responses with movements rightward of the target. No significant correlations were found in adults. This result suggests that in children, motor control and mental rotation may be related through orientation specification processes.

Cerebellar lesion studies of cognitive function in children and adolescents - limitations and negative findings.

An increasing number of human lesion and functional brain imaging studies appear to support the hypothesis that the cerebellum contributes to a wide range of non-motor functions, including attention, language and visuospatial functions. Various abnormalities have been reported in standard neuropsychological tests in children and adolescents who have been treated for cerebellar tumors. This review focuses on limitations of lesion studies and negative findings in children and adolescents with focal cerebellar lesions. Frequently cited early findings have not been replicated in later studies or have been explained by motor components of the tasks. Such discrepancies may relate to a number of methodological problems. In addition to impaired motor function, it is unclear to what extent deficits in neuropsychological tests are caused by unspecific effects such as increased intracranial pressure and depression. Effects of extracerebellar lesions are frequently not considered. Although a role of the cerebellum in specific aspects of non-motor functions seems obvious it is still an open question which cognitive functions are involved, why and to what extent. It is a matter of ongoing discussion whether or not cognitive dysfunction belongs to the symptoms of cerebellar disease. Overall, disorders appear to be mild and far less frequent than disorders observed following lesions of cerebral areas. The aim of the review is to demonstrate that many findings frequently cited to support cerebellar involvement in cognition are insufficient to prove the hypothesis. There is ongoing need of well-controlled lesion studies, which show that disorders are due to cerebellar lesions independent of motor dysfunction and other confounding factors.

Patients with chronic focal cerebellar lesions show no cognitive abnormalities in a bedside test.

The aim of the present study was to show whether cognitive deficits are present in chronic cerebellar patients using a self-developed, validated bedside screening test. Twenty-one adults with a history of infarction within the territory of the posterior-inferior (PICA) or the superior cerebellar artery (SCA), and 25 age-, sex-, and education-matched healthy controls participated. Lesion localization was based on individual 3D MRI scans. The test took 10-12 min including subtests of naming, executive functions, attention, figural and verbal memory, reading, long-term memory, mental arithmetic, higher order motor control, and spatial functions. Though individual patients tended to make more errors than controls, neither total error score nor subscores revealed significant group differences. No obvious cognitive deficits appeared to be present in chronic cerebellar patients as assessed by a bedside screening test.

Cognitive functions in patients with MR-defined chronic focal cerebellar lesions.

The aim of the present study was to examine cognitive functions in a group of chronic patients with focal cerebellar lesions. Both effects of localization (anterior vs. posterior lobe) and side (left vs. right cerebellar hemisphere) were of interest. Fourteen patients with infarctions within the territory of the posterior inferior cerebellar artery (PICA) and seven patients with infarctions within the territory of the superior cerebellar artery (SCA) participated. The affected lobules and nuclei were assessed based on 3D MR imaging. The right cerebellar hemisphere was affected in eight PICA and two SCA patients, the left hemisphere in six PICA and four SCA patients. One SCA patient revealed a bilateral lesion. In order to study possible lateralization of functions, subjects performed a language task as well as standard neglect and extinction tests. Moreover, two tests of executive functions were applied. There were no significant group differences apart from a verbal fluency task, in which all cerebellar patients - but especially those with right-sided lesions - were impaired. Voxel-based lesion-symptom mapping (VLSM) revealed that a lesion of the right hemispheric lobule Crus II was associated with impaired performance in the verbal fluency task. In sum, the results showed preserved cognitive abilities in chronic cerebellar patients apart from impairments of verbal fluency in patients with right-cerebellar lesions. The latter findings are in line with the assumption that the right posterolateral cerebellar hemisphere supports functions associated with verbal fluency.

Degree of cerebellar ataxia correlates with three-dimensional mri-based cerebellar volume in pure cerebellar degeneration.

The aim of the present study was to compare the severity of cerebellar ataxia as measured by the International Cooperative Ataxia Rating Scale (ICARS) by Trouillas et al. [ J Neurol Sci 1997;145:205-211] with the cerebellar volume in chronic cerebellar disease. Fifteen patients with pure cerebellar degeneration were investigated. Seven patients suffered from spinocerebellar ataxia type 6, 5 from idiopathic late-onset cerebellar ataxia, 2 from autosomal dominant cerebellar ataxia type III and 1 from episodic ataxia type 2. Volumetric analysis was based on individual three-dimensional MR images. Total ICARS score significantly inversely correlated with the cerebellar volume (r = -0.805, p < 0.0001), correlations between ICARS subscores and cerebellar volume were significant for upper and lower limb ataxia, ataxia of posture and gait, and dysarthria, but not for the oculomotor subscore. The results suggest that the degree of cerebellar atrophy in pure cerebellar degenerative disorders is accompanied by comparable functional impairment (i.e. degree of cerebellar ataxia).

Adaptation to separate kinematic and dynamic transformations in children and adults.

The question addressed in the present study is whether children and adults are able to combine and decompose separate kinematic (visual-feedback-shift) and dynamic (velocity-dependent force) transformations in goal-directed arm movements. A total of 64 participants (32 adults and 32 children) performed horizontal forearm movements using a single-joint arm manipulandum. When participants first learned kinematic and dynamic transformations separately, target error decreased in a subsequent combined transformation task. This effect was based on previous learning of the kinematic transformation. When they first learned the combined transformation, target error was smaller in the following kinematic-but not in the dynamic-transformation. No difference was found in adaptation performance between children and adults. The results suggest that there are two separate models for the kinematic and dynamic transformation and that a possible differentiation of kinematic and dynamic features of the motor task might already be present at age 11.