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Photoautotrophically growing cultures of the fresh water cyanobacterium Anacystis nidulans adapted to the presence of 0.4-0.5 M NaCl (about sea water level) with a lag phase of two days after which time the growth rate reassumed 80-90% of the control. Plasma and thylakoid membranes were separated from cell-free extracts of French pressure cell treated Anacystis nidulans by discontinuous sucrose density gradient centrifugation and purified by repeated recentrifugation on fresh gradients. Identity of the plasma and thylakoid membrane fractions was confirmed by labeling of intact cells with impermeant protein markers prior to breakage and membrane isolation. Electron microscopy revealed that each type of membrane was obtained in the form of closed and perfectly spherical vesicles. Major changes in structure and function of the plasma membranes (and, to a much lesser extent, of the thylakoid membranes) were found to accompany the adaptation process. On the average, diameters of plasma membrane vesicles from salt adapted cells were only one-third of the diameters of corresponding vesicles from control cells. By contrast, the diameters of thylakoid membrane vesicles were the same in both cases. Freeze-etching the cells and counting the number of membrane-intercalating particles on both protoplasmic and exoplasmic fracture faces of plasma and thylakoid membranes indicated a roughly 50% increase of the particle density in plasma membranes during the adaptation process while that in thylakoid membranes was unaffected. Comparison between particle densities on isolated membranes and those on corresponding whole cell membranes permitted an estimate as to the percentage of inside-out and right-side-out vesicles. Stereometric measurement of particle sizes suggested that two distinct sub-populations of the particles in the plasma membranes increased during the adaptation process, tentatively correlated to the cytochrome oxidase and sodium-proton antiporter, respectively. The effects of salt adaptation described in this paper were fully reversed upon withdrawal of the additional NaCl from the growth medium ('deadaptation'). Moreover, they were not observed when the NaCl was replaced by KCl. [ABSTRACT FROM AUTHOR]

Background: Delirium is a neuropathological syndrome that is characterised by fluctuating impairments in attention, cognitive performance, and consciousness. Since delirium represents a medical emergency, it can be associated with adverse clinical and economic outcomes. Although nursing home residents face a high risk of developing delirium, health care professionals in this field appear to have limited knowledge of delirium despite the critical role they play in the prevention, diagnosis, and treatment of delirium in nursing homes., Objective: The purpose of this realist review is to develop an initial programme theory with the goal of understanding how, why, and under what circumstances educational interventions can improve the delirium-specific knowledge of health care professionals in nursing homes., Methods: This realist review was conducted in accordance with the RAMESES (Realist And Meta-narrative Evidence Synthesis: and Evolving Standards) guidelines and includes the following steps: (1) search strategy and literature review; (2) study selection and assessment; (3) data extraction; (4) data synthesis; and (5) development of an initial programme theory. It also included stakeholder discussions with health care professionals recruited from nursing home care, which focused on their experiences with delirium., Results: From a set of 1703 initially identified publications, ten publications were included in this realist review. Based on these publications, context-mechanism-outcome configurations were developed; these configurations pertained to (1) management support, (2) cognitive impairments among residents, (3) familiarity with residents, (4) participatory intervention development, (5) practical application, (6) case scenarios, (7) support from experts and (8) relevance of communication., Conclusions: Educational interventions aimed at improving the delirium-specific knowledge of health care professionals should feature methodological diversity if they are to enhance health care professionals' interest in delirium and highlight the fundamental contributions they make to the prevention, diagnosis, and treatment of delirium. Educational interventions should also take into account the multidimensional contextual factors that can have massive impacts on the relevant mode of action as well as the responses of health care professionals in nursing homes. The identification of delirium in residents is a fundamental responsibility for nursing home staff., Trial Registration: This review has been registered at Open Science Framework https://doi.org/10.17605/OSF.IO/6ZKM3., (© 2024. The Author(s).)

Background: Patients suffering from complex regional pain syndrome (CRPS) are increasingly shown to be affected by cognitive difficulties. While these cognitive symptoms were initially described as limited to the perception, representation and use of the body, that is, the somatic space, they were recently shown to also extend to the perception of extra-somatic space. CRPS patients seem indeed to pay less attention to visual stimuli occurring in the same side of space as their affected limb and especially those occurring close to that limb. The aim of the present study was to more precisely characterize these visuospatial biases, by investigating whether they may be dependent on the visually perceived proximity between the visual stimuli and the affected limb., Methods: Upper-limb CRPS patients and matched control participants performed temporal order judgements on visual stimuli, one presented in either side of space, while they could either see their hands near the visual stimuli or not., Results: Visuospatial biases were not modulated by the availability of visual feedback about the hands. However, secondary analyses revealed that these biases depended on the type of rehabilitation program that the patients followed: whereas patients who did not follow any specific program presented significant biases to the detriment of visual stimuli in the affected side of space, patients who did follow a CRPS-specialized program did not., Conclusions: Patients' cognitive strategies will be important to consider when studying inter-individual differences in the cognitive symptomatology and associated cognitive-based rehabilitation procedures in CRPS., Significance: The existence of biases in visuospatial perception in Complex Regional Pain Syndrome has been reported but not always systematically replicated. We show that these biases might depend on the type of general rehabilitation program that the patients follow. Patients' individual cognitive strategies will be important to consider when studying the cognitive symptomatology of CRPS., (© 2023 European Pain Federation - EFIC ®.)

Background: Delirium is a neuropathological condition that impairs cognitive performance, attention and consciousness and can be potentially life-threatening. Nursing home residents are particularly vulnerable to developing delirium, but research thus far tends to focus on the acute hospital setting. Healthcare professionals (HCPs) working in nursing homes seem to be little aware of delirium. To improve healthcare for affected or at-risk individuals, increasing knowledge among HCPs is highly relevant. Using the realist review method helps to understand how and why an educational intervention for HCPs on delirium in nursing homes works., Methods and Analysis: In accordance with the Realist And Meta-narrative Evidence Syntheses: Evolving Standards publication standards for realist syntheses, the review process will include the following five steps: (1) search strategy and literature review; (2) study selection and assessment; (3) data extraction; (4) data synthesis and (5) development of an initial programme theory. The literature search will be conducted in the databases Medline (PubMed), CINAHL (Ebsco), Scopus, Web of Science, GeroLit and Carelit. Additional focuses are on snowballing techniques, hand research and grey literature. Studies of any design will be included to develop the initial programme theory. The literature will be selected by two researchers independently. In addition, the experiences of HCPs from nursing homes will be reflected in group discussions. To this end, Context-Mechanism-Outcome configurations (CMOcs) will be established to develop an initial programme theory., Ethics and Dissemination: The results will be disseminated within the scientific community. For this purpose, presentations at scientific conferences as well as publications in peer-reviewed journals are scheduled. In the next step, the CMOcs could serve for the development of a complex educational intervention to increase the knowledge of HCPs on delirium in nursing homes., Registration Details: This protocol has been registered at Open Science Framework (https://doi.org/10.17605/OSF.IO/HTFU4)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To protect our body against physical threats, it is important to integrate the somatic and extra-somatic inputs generated by these stimuli. Temporal synchrony is an important parameter determining multisensory interaction, and the time taken by a given sensory input to reach the brain depends on the length and conduction velocity of the specific pathways through which it is transmitted. Nociceptive inputs are transmitted through very slow conducting unmyelinated C and thinly myelinated Aδ nociceptive fibers. It was previously shown that to perceive a visual stimulus and a thermo-nociceptive stimulus applied on the hand as coinciding in time, the nociceptive stimulus must precede the visual one by 76 ms for nociceptive inputs conveyed by Aδ fibers and 577 ms for inputs conveyed by C fibers. Since spatial proximity is also hypothesized to contribute to multisensory interaction, the present study investigated the effect of spatial congruence between visual and nociceptive stimuli. Participants judged the temporal order of visual and nociceptive stimuli, with the visual stimuli flashed either next to the stimulated hand or next to the opposite unstimulated hand, and with nociceptive stimuli evoking responses mediated by either Aδ or C fibers. The amount of time by which the nociceptive stimulus had to precede the visual stimulus for them to be perceived as appearing concomitantly was smaller when the visual stimulus occurred near the hand receiving the nociceptive stimulus as compared to when it occurred near the contralateral hand. This illustrates the challenge for the brain to process the synchrony between nociceptive and non-nociceptive stimuli to enable their efficient interaction to optimize defensive reaction against physical dangers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Epidermal growth factor receptor inhibitors (EGFRI) are used as targeted cancer therapy. On average 70% of patients treated with EGFRIs suffer from skin toxicity. Studies showed a correlation between overall survival and the appearance of a skin rash, which is used as a biomarker for therapy efficacy. Micro RNAs (miRNA) as tumor or resistance biomarkers for cancer therapy are also highly investigated. In our study, we searched for associations of miRNA expression profiles in serum, with the severity of skin rash, in order to identify tentative therapy predictive biomarkers., Materials and Methods: Five candidate miRNAs were selected, based on an earlier in vitro next-generation-sequencing-experiment and after literature search. MiR-21, miR-31, miR-17, miR-106b and miR-520e were investigated in serum samples from patients ( n = 254) treated with EGFRI. The quantitative expression of miRNA was tested for association with the occurrence/severity of the rash., Results: In our cohort of patients treated with EGFR inhibiting monoclonal antibodies, miR-21 and miR-520e serum concentrations were negatively correlated with severity of skin rash ( p -value 0.000582 and 1.53e-07 linear-trend-test) whereas for miR-31, a positive correlation was observed ( p -value 9.01e-06 linear-trend-test)., Conclusions: This suggests that miR-21, miR-31 and miR-520e expression might be a treatment dependent marker for EGFRI induced skin rash., Competing Interests: CONFLICTS OF INTEREST Authors have no conflicts of interest to declare., (Copyright: © 2021 Kemski et al.)

Canine atopic dermatitis (CAD) is an allergic skin disease associated with IgE and IgG antibodies (Ab) to environmental allergens. The aim of this study was to determine which other factors influence serum Ab levels in CAD-affected and non-affected dogs as this has only been poorly investigated in dogs so far. Total and allergen-specific IgE levels and Dermatophagoides farinae (DF)-specific IgG1 and IgG4 were measured by ELISA in sera of 145 CAD-affected and 271 non-affected Labrador- and Golden retrievers. A multivariable logistic regression analysis including the factors age, breed, gender, castration, clinical CAD status and allergen-specific immunotherapy (ASIT) was performed. Golden retrievers had more frequently total (OR=1.87, 95% CI=1.26-2.87, p<0.01) and specific IgE levels above the threshold value than Labrador retrievers, suggesting that genetic factors influence IgE levels in dogs. Castration was generally associated with low Ab levels (OR=0.43-0.65, p<0.05). Surprisingly, dogs with CAD did not have increased odds for high IgE against any of the allergens tested. ASIT with DF was associated with high DF-specific IgG1 (OR=4.32, 95% CI 1.46-12.8, p<0.01) but was not associated with DF-specific IgG4 or decreased IgE levels. Further studies are needed to understand the role of allergen-specific IgE in CAD and of IgG1 in ASIT., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Crosslinking of immunoglobulin E antibodies (IgE) bound at the surface of mast cells and subsequent mediator release is considered the most important trigger for allergic reactions. Therefore, the genetic control of IgE levels is studied in the context of allergic diseases, such as asthma, atopic rhinitis, or atopic dermatitis (AD). We performed genome-wide association studies in 161 Labrador Retrievers with regard to total and allergen-specific immunoglobulin E (IgE) levels. We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro. We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5. A. siro and T. putrescentiae both belong to the family Acaridae and represent so-called storage or forage mites. These forage mites are discussed as major allergen sources in canine AD. No obvious candidate gene for the regulation of IgE levels is located under the two association signals. Therefore our studies offer a chance of identifying a novel mechanism controlling the host's IgE response.

Photoautotrophically growing cultures of the freshwater cyanobacterium Anacystis nidulans (Synechococcus sp.) became adapted to the presence of 0.4-0.5 M NaCl in the growth medium (about seawater level) with a lag phase of 2 days after which time the growth rate resumed at 80-90% of the control. Major changes in structure and function of the plasma membranes (and, to a much lesser extent, of the thylakoid membranes) were found to accompany the adaptation process. Plasma and thylakoid membranes were separated from crude cell-free extracts of French pressure cell-treated Anacystis by discontinuous sucrose density gradient centrifugation and purified by repeated recentrifugation on fresh gradients. Concentrations of copper, iron, calcium, and magnesium ions were determined by inductively coupled plasma atomic emission spectrometry with EDTA-washed and dialyzed membrane preparations; salt adaptation was found to increase (decrease) the concentration of membrane-bound calcium in plasma (thylakoid) membranes, qualitatively reciprocal results being obtained for magnesium. Levels of plasma membrane-bound copper and iron roughly tripled during the adaptation process; by contrast, corresponding effects on thylakoid membranes were negligible. The size of the membrane vesicles was measured by quasi-elastic laser light-scattering and the electric surface charge of the membranes was measured by laser Doppler velocimetry. Salt adaptation decreased the mean diameter of plasma membrane vesicles to a much higher extent than that of thylakoid membrane vesicles. Overall surface charge densities of resting vesicles were only slightly affected by the salt treatment as was also seen from titration of the electrophoretic mobility of the vesicles with electrolytes. Yet, induction of (photosynthetic or respiratory) electron transport provoked a charge separation across the membrane which was easily measurable in terms of electrophoretic mobility. The results will be discussed with particular emphasis on the stimulated cytochrome c oxidase activity of plasma (but not thylakoid) membranes from salt-adapted cells compared to control cells and also with respect to the decreased ion permeability of the plasma membrane of salt grown cells.

Functionally intact plasma membranes were isolated from the cyanobacterium (blue-green alga) Anacystis nidulans through French pressure cell extrusion of lysozyme/EDTA-treated cells, separated from thylakoid membranes by discontinuous sucrose density gradient centrifugation, and purified by repeated recentrifugation. Origin and identity of the chlorophyll-free plasma membrane fraction were confirmed by labeling of intact cells with impermeant protein markers, [35S]diazobenzenesulfonate and fluorescamine, prior to membrane isolation. Rates of oxidation of reduced horse heart cytochrome c by purified plasma and thylakoid membranes were 90 and 2 nmol min-1 (mg of protein)-1, respectively. The cytochrome oxidase in isolated plasma membranes was identified as a copper-containing aa3-type enzyme from the properties of its redox-active and EDTA-resistant Cu2+ ESR signal, the characteristic inhibition profile, reduced minus oxidized difference spectra, carbon monoxide difference spectra, photoaction and photodissociation spectra of the CO-inhibited enzyme, and immunological cross-reaction of two subunits of the enzyme with antibodies against subunits I and II, and the holoenzyme, of Paracoccus denitrificans aa3-type cytochrome oxidase. The data presented are the first comprehensive evidence for the occurrence of aa3-type cytochrome oxidase in the plasma membrane of a cyanobacterium similar to the corresponding mitochondrial enzyme (EC 1.9.3.1).