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Background: Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis, and mainly transmitted via faecal-oral contamination or consumption of contaminated food products. However, limited data on the surface stability and HEV sensitivity to chemical disinfectants are available., Aim: To establish an HEV-based carrier assay to evaluate its surface stability and the virucidal activity of nine surface disinfectants., Methods: A recently developed robust HEV-3 cell culture system for an HEV-based carrier assay., Findings: Alcohol-based disinfectants were insufficient to eliminate HEV infectivity, whereas disinfectants based on aldehyde, peracetic acid, oxygen, and/or quaternary ammonium inactivated HEV., Conclusion: These findings have strong implications for the recommendation of evidence-based hygiene guidelines to reduce HEV transmission., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate the pacemaker current which plays an important role in the timing of various biological processes like the heart beat. We used umbrella sampling to explore the potential of mean force for the conduction of potassium and sodium through the open HCN4 pore. Our data explain distinct functional features like low unitary conductance and weak selectivity as a result of high energetic barriers inside the selectivity filter of this channel. They exceed the 3-5 kJ/mol threshold which is presumed as maximal barrier for diffusion-limited conductance. Furthermore, simulations provide a thermodynamic explanation for the weak cation selectivity of HCN channels that contain only two ion binding sites in the selectivity filter (SF). We find that sodium ions bind more strongly to the SF than potassium and are easier released by binding of potassium than of another sodium. Hence ion transport and selectivity in HCN channels is not determined by the same mechanism as in potassium-selective channels; it rather relies on sodium as a weak blocker that can only be released by potassium., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Physiological Society.)

Introduction: The aim of the present study was to probe electrophysiological effects of non-symbolic numerical processing in 20 children with mathematical learning disabilities (mean age = 99.2 months) compared to a group of 20 typically developing matched controls (mean age = 98.4 months)., Methods: EEG data were obtained while children were tested with a standard non-symbolic numerical comparison paradigm that allowed us to investigate the effects of numerical distance manipulations for different set sizes, i.e., the classical subitizing, counting and estimation ranges. Effects of numerical distance manipulations on event-related potential (ERP) amplitudes as well as activation patterns of underlying current sources were analyzed., Results: In typically developing children, the amplitudes of a late parietal positive-going ERP component showed systematic numerical distance effects that did not depend on set size. For the group of children with mathematical learning disabilities, ERP distance effects were found only for stimuli within the subitizing range. Current source density analysis of distance-related group effects suggested that areas in right inferior parietal regions are involved in the generation of the parietal ERP amplitude differences., Conclusion: Our results suggest that right inferior parietal regions are recruited differentially by controls compared to children with mathematical learning disabilities in response to non-symbolic numerical magnitude processing tasks, but only for stimuli with set sizes that exceed the subitizing range., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Whether and in what way enumeration processes differ for small and large sets of objects is still a matter of debate. In order to shed light on this issue, EEG data were obtained from 60 normally developing elementary school children. Adopting a standard non-symbolic numerical comparison paradigm allowed us to manipulate numerical distance between stimulus arrays for different quantity ranges, i.e. the subitizing, counting and estimation ranges. In line with the existing literature, the amplitudes of parietal positive going ERP components showed systematic effects of numerical distance, which did not depend on set size. In contrast to the similarities in surface distribution of electrophysiological activity across all number ranges, applying source localization we found distance related current density effects in inferior parietal processing systems to be similar for all numerical ranges, there was, however, considerable variation in the involvement of medial parietal and lateral occipital regions. The precuneus, which is known to be involved in visual imagery, showed distance effects exclusively for numerical comparisons on large set sizes. In contrast, the processing of small quantities and stimulus arrays arranged into canonical patterns relied on lateral occipital areas that are linked to higher-level shape recognition. These findings suggest, on the one hand, that for explicit numerical decisions an involvement of domain-specific resources does not depend on quantity features of the visual input. On the other hand, it seems that the recruitment of mediating perceptual systems differs between the apprehension of small quantities and the enumeration of large sets of objects., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Theoretical support is evaluated for nursing students' use of an innovative educational intervention, the Psychopharmacology R.A.C.E. (Wissman and Tankel, Kansas City, MO) game, as an empowerment tool with mental health clients. Based on mutual trust and respect, the interpersonal process occurs between an individual or group (e.g., client, student) with a desire for competency growth (e.g., knowledge, proactive health behaviors, negotiation), and development of a sense of control and self-determination and another individual or group (e.g., nurse) who serves as an enabler, supporter, and resource mobilizer. A review of empowerment literature identifies: (1) support of education as an empowerment tool; (2) identification of specific teaching methods and behaviors that promote empowerment; (3) empowerment as an outcome of involvement; and (4) support of the empowerment value of group participation. Preliminary clinical observations reveal strong support for nursing students' use of the Psychopharmacology R.A.C.E. game as a method to empower mental health clients.

This account reports on the development and function of novel substrate mimetics as artificial substrates for Glu-specific endopeptidases. Firstly, in an empirical way, various aliphatic and aromatic analogs of the already established carboxymethyl thioester-substrate mimetics were designed from simple structure-function relationship studies. The specificity of the newly developed substrates for Staphylococcus aureus V8 protease-catalyzed reactions have been examined by steady-state hydrolysis kinetic studies. Additionally, these studies were expanded to the use of the equally Glu-specific endopeptidase from Bacillus licheniformis (BL-GSE) which can easily be purified from alcalase in high yields. Finally, the novel substrate mimetics were used as acyl donor components in BL-GSE- and V8 protease-catalyzed model acyl transfer reactions. The results clarify the newly developed substrate mimetics as efficient acyl donors as well as BL-GSE as an attractive alternative to V8 protease for enzymatic peptide synthesis.

1 In this era of rapidly changing mental health services and new psychotropic drugs, health professionals are challenged to develop and maintain psychopharmacology competencies. 2 The Psychopharmacology RACE provides an interactive and learner-oriented method of developing and assessing theoretical and clinical competencies for psychopharmacology. 3 The Psychopharmacology RACE is also well suited for modification and application toward the professional development of nurses and the education of clients.

The reverse action of a trypsin-free elastase isolated from porcine pancreas was studied in frozen aqueous systems. Under frozen state conditions, porcine pancreatic elastase was able to catalyse peptide bond formation more effectively than in solution at room temperature. The acceptance of free amino acids as nucleophilic amino components indicates a changed specificity of the endoprotease in frozen reaction mixtures. In elastase-catalysed formation of Ser-, Ile- and Val-X-bonds in frozen aqueous reaction mixtures, peptide yields obtained depended on the P1 amino acid and the acyl donor chain length.

Annexins were isolated from Paramecium cell homogenates by standard ethylene glycol tetraacetic acid (EGTA) extraction and 100 000-g centrifugation. Two different antibodies (Abs) against synthetic peptides were used, Call-15 and B15, which in mammalian cells recognize a sequence of annexin II or a common sequence occurring in several annexins (except for annexin II), respectively. With anti-Call-15 Abs, western blots from EGTA extracts showed strongly reactive bands of 44.5 and 46 kDa and of higher values. Some of these bands bound to the 100 000-g pellet fraction when Ca(2+) was added. Immuno- and affinity labelling revealed selective, Ca(2+)-dependent labelling of the cell cortex, with enrichment around trichocyst docking sites (facing subplasmalemmal Ca(2+) stores). Cortical fluorescence labelling decreased in wild-type (7S) cells when trichocyst ghosts were detached after synchronous exocytosis. Similarly, cortical labelling was reduced when intact trichocysts were detached from the cell surface of non-discharge mutant cells (nd9-28 degrees C, showing identical bands on blots), which then contained numerous heavily labelled phagolysosomes. This strongly suggests annexin downregulation. All together, the dynamic labelling of cortical structures we observed strongly supports involvement of calpactin-like annexins in trichocyst docking. Anti-B15 Abs recognized a band of 51 kDa and some of higher values. These Abs selectively labelled the outlines of the cytoproct, the site of spent phagolysosome exocytosis. In conclusion, our data indicate involvement of specific sets of annexins in site-specific positioning and attachment of widely different secretory organelles at the cell surface in Paramecium cells.

Caffeine inhibits 45Ca2+ sequestration by subplasmalemmal calcium stores ('alveolar sacs') of low thapsigargicin sensitivity which we have isolated from the ciliated protozoan, Paramecium tetraurelia. Inhibition depends on caffeine concentration, with an IC50 of 31.8 mM. According to kinetic evaluation this is compatible with non-competitive inhibition of Ca2+ uptake, rather than with superimposed 45Ca2+ release during sequestration. It remains to be analysed whether this mechanism might be of possible relevance also for Ca2+-mediated activation in vivo in this or in any other secretory system. Such an effect could also operate indirectly, e.g., by Ca2+-release induction via sequestration inhibition. This is the first description of caffeine-mediated inhibition of Ca2+ uptake by calcium stores from a secretory system. Our data are compatible with some observations with sarcoplasmic reticulum from striated muscle fibers.

The author presents six strategies that have been used successfully to teach and assess critical-thinking skills in a pharmacology course. Within the context of pharmacology content, the strategies were designed to develop student abilities in making critical distinctions, critical decision making, analysis of assessment findings, and the anticipation of intervention results and possible side effects/consequences.

Senior citizens commonly take multiple medications and lack knowledge about proper use and side effects. They often have no access to health professionals to clarify any misconceptions about their medications. Nursing students often learn pharmacology in the classroom with no opportunity to apply the knowledge as it is learned. Within one community, a creative strategy was developed to meet the learning needs of both groups. At a local senior center, clients with drug-knowledge deficits or compliance difficulties were identified. Pharmacology nursing students were then assigned to collect drug histories from these clients. Following analysis of gathered data, students were required to develop individualized drug teaching tools for their assigned client. Through these activities, the learning needs of both groups were met.

The author describes a teaching-learning strategy that helped students gain an enhanced appreciation for nursing theories and their application to nursing practice. Students selected, campaigned for, and elected a nursing theorist to serve as Vice President for a Nursing Theory Club. Through the campaign and election process, they were able to select and investigate a nursing theorist and apply the theorists' work to nursing practice. Campaign materials, campaign headquarter displays, and campaign speeches allowed for assessment of many program outcomes including effective written and verbal communication, critical thinking, professionalism, empiric knowledge, and aesthetics.

The following data were obtained from 36 male chronic schizophrenics (ICD 295.6) of 47 +/- 11 years of age, treated with neuroleptics for the last 16 +/- 6 years: Age, age at first manifestation of disease, duration and dosage scheme of neuroleptic therapy and number of electroconvulsive shock treatments. Blood samples were drawn both under neuroleptic treatment and after a 12-day withdrawal of neuroleptics, for determining cortisol, prolactin, beta-endorphin and noradrenaline. Psychopathology was assessed by standard criteria via BPRS. In 27 patients CT determination was carried out to determine the breadth of the third ventricle and the ventricular brain ratio. Withdrawal of neuroleptics resulted in a marked improvement, whereas 11 patients showed pronounced deterioration of their psychotic symptoms. In respect of the entire group there was a significant improvement of anergy, while disturbances of thinking were significantly enhanced. Serum levels of beta-endorphin and cortisol increased after neuroleptic withdrawal, whereas the levels of prolactin and of noradrenaline dropped. A considerable proportion of the patients showed a distinct extension of the ventricular system, but the CT variables correlated only slight with psychopathological parameters or their changes after neuroleptic withdrawal. The other variables, too, were without clinically relevant prognostic importance compared with the psychopathological changes after neuroleptic withdrawal. These variables were e.g. demography, psychopathology, therapy and neuroendocrinology.

The psychopathology of 36 chronic, schizophrenic patients who had been on maintenance neuroleptics was rated during neuroleptic therapy and after 12 days of neuroleptic withdrawal. At both times, hormonal serum levels were also determined. Moreover, in 27 of these patients, ventricle-brain ratio, maximal width of the third ventricle, and sulcal widening were measured on computed tomography (CT). Neuroleptic withdrawal resulted in individually different psychopathological changes: 7 patients improved, 11 worsened. Within the whole group, thought disorder deteriorated, and anergia improved. Levels of cortisol and beta-endorphin increased; those of prolactin and norepinephrine decreased. The majority of patients showed ventricular enlargement, which was marginally related to reduced thought disorder. CT and endocrine variables were slightly related to psychopathology or psychopathological effects of neuroleptic withdrawal.