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Two L-lysine-derived salicylidene ligands have been synthesized under ultrasound irradiations and characterized by several spectroscopic techniques. Both ligands exhibited a blue fluorescence emission in ethanolic solutions. (S, E)-3-Amino-7-((2-hydroxybenzylidene) amino) heptanoic acid (A) and (S, E)-3-amino-7-((4-chloro-2-hydroxybenzylidene) amino) heptanoic acid (B) showed a turn-off sensing of Cu2+ and Co2+ cations, respectively, over several tested transition metal cations such as Fe2+, Zn2+, Cr3+, Co2+, Ni2+ and Cu2+ in aqueous media. The ability of both tested L-lysine-derived ligands (A) and (B) to distinguish Cu2+ and CO2+, respectively, has been verified by optical studies, showing new absorption bands around 304 and 391 nm for (A)-Cu2+ and a new band around 455 nm for (B)-Co2+ along with the disappearance of the original bands supporting thereby the noticed Turn–Off results. [ABSTRACT FROM AUTHOR]

The Score Committee of the European Foot and Ankle Society (EFAS) developed, validated, and published the EFAS Score in 13 languages. Currently, the Danish version completed data acquisition and underwent further validation. The data were collected pre-operatively and post-operatively at a minimum follow-up of 3 months and mean follow-up of 6 months. Item reduction, scale exploration, confirmatory analyses and responsiveness were executed using classical test theory and item response theory. The internal consistency was confirmed in the Danish version (Cronbach's Alpha 0.88). The Standard Error of Measurement (SEM) was 0.31 and is similar to other language versions. Between baseline and follow-up, 77.2% of patients showed an improvement on their EFAS score, with adequate responsiveness (effect size 1.05). The Danish EFAS Score version was successfully validated in patients with a wide variety of foot and ankle pathologies. All score versions are freely available at www.efas.net. [ABSTRACT FROM AUTHOR]

Emotional prospective mental imagery, in which we simulate possible future events within our minds, have a pronounced impact on behavior. For example, repeated engagement in positive prospective imagery can lead to behavioral activation, while negative prospective imagery can lead to catastrophizing and avoidance. Physiological arousal boosts memory consolidation, creating emotional memories. Thus, if emotional prospective imagery produces an arousal response, the memory consolidation of these simulations of the future may be boosted, offering a possible underlying mechanism for the impact of emotional prospective imagery on behavior. In order to examine the feasibility of arousal as a possible mechanism behind the impact of emotional prospective imagery on behavior, sixty participants produced autobiographical prospective imagery of 30 scenes (10 positive, 10 neutral, and 10 negative), during which arousal responses (skin conductance) were measured, and ratings for subjective arousal, valence, and imagery vividness were collected. Moreover, because vividness of prospective imagery has been related to anxiety and depression, the study examined this relation also for event-related autobiographical prospective imagery. The results showed that emotional prospective imagery were associated with higher subjective arousal ratings as compared to neutral imagery. Physiological arousal responses showed a similar pattern, but further data is needed for a firm conclusion. Nevertheless, arousal-boosted consolidation remains a possible contributing mechanism for the impact of emotional prospective imagery on behavior. Moreover, results suggest both anxiety and depression may entail a reduced ability to invent prospective life situations. However, only anxiety was associated with less vivid imaginations, unless the imaginations were of negative content. Hence, anxious individuals may experience negative prospective imagery more vividly than imagery with neutral and positive content. [ABSTRACT FROM AUTHOR]

Imaginal exposure is a standard procedure of cognitive behavioral therapy for the treatment of anxiety and panic disorders. It is often used when in vivo exposure is not possible, too stressful for patients, or would be too expensive. Peter Lang's Bio‐Informational Theory implies that imaginal exposure is effective because of the perceptual proximity of mental imagery to real events, whereas empirical findings suggest that propositional thought of fear stimuli (i.e., thinking about the stimuli without seeing them in the mind's eye) could be sufficient in therapeutical contexts. Exposure to propositional thought, instead of vivid mental imagery, would be more tolerable for patients since vivid imagery is associated with high emotional distress. To investigate whether mental imagery or propositional thought is crucial for the success of imaginal exposure, participants with the rare state of aphantasia (= absence of sensory mental imagery but with intact propositional thought) and two control groups were subjected to a fear conditioning paradigm followed by imaginal exposure and a reinstatement procedure. During imaginal exposure, control group 1 (N = 30) stared at a bright screen to disrupt visual imagery by incoming luminance (= simulated aphantasia), whereas control group 2 (N = 30) and participants with actual aphantasia (N = 30) kept their eyes closed. The results show [...]. Our research investigates the mechanisms underlying Imaginal Exposure Therapy contrasting the fear response of people with aphantasia (= absence of visual imagery), simulated aphantasia, and controls after imaginal extinction to test whether the success of imaginal exposure depends on mental imagery or whether propositional thought is sufficient. The results have far‐reaching consequences for the implementation of Imaginal Exposure Therapy, for example, in enabling the reduction of emotional distress and therapy dropout. [ABSTRACT FROM AUTHOR]

The Score Committee of the European Foot and Ankle Society (EFAS) developed, validated, and published the EFAS Score in 11 languages (Dutch, English, German, Finnish, French, Italian, Polish, Portuguese, Persian, Swedish, Turkish). From other languages under validation, the Spanish and Estonian versions completed data acquisition and underwent further validation. The EFAS Score was developed and validated in three stages: 1) item (question) identification (completed during the initial validation study), 2) item reduction and scale exploration (completed during the initial validation study), 3) confirmatory analyses and responsiveness of the Spanish and Estonian versions (completed during the initial validation study in seven other languages). The data were collected pre-operatively and post-operatively at a minimum follow-up of 3 months and mean follow-up of 6 months. Item reduction, scale exploration, confirmatory analyses and responsiveness were executed using classical test theory and item response theory. The internal consistency of the scale was confirmed in the Spanish and Estonian versions (Cronbach's Alpha>0.8). Responsiveness was good, with moderate to large effect sizes in both languages, and evidence of a statistically significant positive association between the EFAS Score and patient-reported improvement. The Spanish and Estonian EFAS Score versions were successfully validated in orthopaedic ankle and foot surgery patients, with a wide variety of foot and ankle pathologies. All score versions are freely available at www.efas.net. [ABSTRACT FROM AUTHOR]

In order to increase the ability to build complex, software-intensive systems, as well as to decrease time-to-market for new functionality, automotive companies aim to scale agile methods beyond individual teams. This is challenging, given the specifics of automotive systems that are often safety-critical and consist of software, hardware, and mechanical components. In this article, we investigate the concrete reasons for scaling agility beyond teams, the strategies that support such scaling, and the foreseeable implications that such a drastic organizational change will entail. The investigation is based on a qualitative case study, with data from 20 semistructured interviews with managers and technical experts at two automotive companies. At the core of our findings are observations about establishing an agile vehicle-level feedback loop beyond individual teams. First, we find that automotive original equipment manufacturers aim to decrease the lead time of development. Second, we also identify seven strategies that aim to enable scaled-agile beyond teams. Finally, we extract six foreseeable implications and side effects of scaling agile beyond teams in automotive. By charting the landscape of expected benefits, strategies, and implications of scaling agile beyond teams in automotive, we enable further research and process improvements. [ABSTRACT FROM AUTHOR]

Background: The Score Committee of the European Foot and Ankle Society (EFAS) developed, validated, and published the EFAS Score in ten languages (English, German, French, Italian, Polish, Dutch, Swedish, Finnish, Turkish, Portuguese). From other languages under validation, the Portuguese version completed data acquisition and underwent further validation.Methods: The Portuguese version of the EFAS Score was developed and validated in three stages: 1) item (question) identification (completed during initial validation study), 2) item reduction and scale exploration (completed during initial validation study), 3) confirmatory analyses and responsiveness of Portuguese version (completed during initial validation study in nine other languages). The data were collected pre-operatively and post-operatively at a minimum follow-up of 3 months and mean follow-up of 6 months. Item reduction, scale exploration, confirmatory analyses and responsiveness were executed using classical test theory and item response theory.Results: The internal consistency was confirmed in the Portuguese version (Cronbach's Alpha 0.84). The Standard Error of Measurement (SEM) was 0.27 and is similar to other language versions. Between baseline and follow-up, 69.4% of patients showed an improvement on their EFAS score, with adequate responsiveness (effect size 0.64).Conclusions: The Portuguese EFAS Score version was successfully validated in patients with a wide variety of foot and ankle pathologies. All score versions are freely available at www.efas.net. [ABSTRACT FROM AUTHOR]

• A new magnetic nanoparticles of magnetite functionalized Schiff base modified nanocellulose [(pH-PDA-DANC)@Fe 3 O 4 NPs] was synthesized by an ecofriendly and a simple protocol. • The synthesized product was characterized using FTIR, XRD, SEM-EDX, and TGA analysis. • The magnetic nano-catalyst [(pH-PDA-DANC)@Fe 3 O 4 NPs] was used subsequently as a catalyst in the green and efficient procedure for one-pot multicomponent syntheses of imidazole derivatives. In the present work, a nanocellulose based magnetic nanocomposite [(pH-PDA-DANC)@Fe 3 O 4 NPs] was synthesized by an ecofriendly and a simple protocol and characterized by means of different techniques such as Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Thermal Gravimetric Analysis (TGA), Scanning Electron Microscopy (SEM) equipped with an Energy Dispersive X-ray (EDX) probe and the Value Stream Mapping (VSM). The theoretical study of [(pH-PDA-DANC)@Fe 3 O 4 NPs] was investigated using Density Functional Theory (DFT) at the DFT-D3/ B3LYP/LanL2DZ level of theory to explore the nature of the interactions between the (pH-PDA-DANC) ligand and magnetite nanoparticles. The results indicate that the Fe 3 O 4 nanoparticles form covalent bonds with the N-ring of the ligand. Then, it was used as a catalyst in the green and efficient procedure for one-pot multicomponent syntheses of imidazole derivatives by the condensation of benzil or 9.10-phenanthrenequinone, benzaldehyde derivatives and ammonium acetate. The catalytic reaction provided the synthesis of above imidazole derivatives with high reaction efficiency (80 %-98.1 %) in a short reaction time (3 h) and in presence of a minimum amount of ethanol. The identification and structure of imidazole derivatives was determined analyzing the 1H NMR (Nuclear Magnetic Resonance) and FTIR spectra. This procedure has several advantages compared to the conventional method such as the high yields, short reaction times, easy separation of the nanocatayst from the reaction mixture by using a magnet, and the reusability of the catalyst. [Display omitted] [ABSTRACT FROM AUTHOR]

• A new magnetic nanoparticles of magnetite functionalized Schiff base modified nanocellulose [(pH-PDA-DANC)@Fe 3 O 4 NPs] was synthesized by an ecofriendly and a simple protocol. • The synthesized product was characterized using FTIR, XRD, SEM-EDX, and TGA analysis. • The magnetic nano-catalyst [(pH-PDA-DANC)@Fe 3 O 4 NPs] was used subsequently as a catalyst in the green and efficient procedure for one-pot multicomponent syntheses of imidazole derivatives. In the present work, a nanocellulose based magnetic nanocomposite [(pH-PDA-DANC)@Fe 3 O 4 NPs] was synthesized by an ecofriendly and a simple protocol and characterized by means of different techniques such as Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Thermal Gravimetric Analysis (TGA), Scanning Electron Microscopy (SEM) equipped with an Energy Dispersive X-ray (EDX) probe and the Value Stream Mapping (VSM). The theoretical study of [(pH-PDA-DANC)@Fe 3 O 4 NPs] was investigated using Density Functional Theory (DFT) at the DFT-D3/ B3LYP/LanL2DZ level of theory to explore the nature of the interactions between the (pH-PDA-DANC) ligand and magnetite nanoparticles. The results indicate that the Fe 3 O 4 nanoparticles form covalent bonds with the N-ring of the ligand. Then, it was used as a catalyst in the green and efficient procedure for one-pot multicomponent syntheses of imidazole derivatives by the condensation of benzil or 9.10-phenanthrenequinone, benzaldehyde derivatives and ammonium acetate. The catalytic reaction provided the synthesis of above imidazole derivatives with high reaction efficiency (80 %-98.1 %) in a short reaction time (3 h) and in presence of a minimum amount of ethanol. The identification and structure of imidazole derivatives was determined analyzing the 1H NMR (Nuclear Magnetic Resonance) and FTIR spectra. This procedure has several advantages compared to the conventional method such as the high yields, short reaction times, easy separation of the nanocatayst from the reaction mixture by using a magnet, and the reusability of the catalyst. [Display omitted] [ABSTRACT FROM AUTHOR]

Magnetic [FA‐c‐(C‐DTX)@Fe3O4] nanocomposites have been prepared with a four‐step technique involving three mechanical stirring conventional steps to obtain [(FA‐c‐(DTX‐g‐DAC)] and an ultrasound‐assisted Fe3O4 coating approach to fabricate [FA‐c‐(C‐DTX)@Fe3O4]. Magnetic nanoparticles (NPs) (Fe3O4 NPs) synthesis and integration has been easily and rapidly approached under novel environmentally friendly optimized reaction conditions: an ethanol–water solution, one iron precursor use, short reaction time, low temperature, and an ultrasonic irradiation process. This new condition's unique combination is attributed to our new synthesis procedure. Sonochemically synthetisized [FA‐c‐(C‐DTX)@Fe3O4] were easily separated from the reaction mixture simply via external magnetic field application, and therefore, neither filtration nor centrifigation was required. The synthetisized samples have been investigated by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, X‐ray photoelectron spectroscopy (XPS), X‐ray diffraction (XRD), thermogravimetry analysis (TGA), scanning electron microscopy (SEM), and vibrating‐sample magnetometry (VSM). Obtained outcomes including successful magnetite coating process, good crystallinity, homogenous morphology, enhanced thermal stability, and obvious magnetic properties suggested the potential of sonochemical procedure to fabricate and integrate magnetic NPs. This sonochemically synthesized catalyst was evaluated toward the reduction of the organic pollutant 4‐nitrophenol and showed excellent catalytic activity. This ultrasound‐assisted nanocomposites preparation is simply scalable to meet industrial application. [ABSTRACT FROM AUTHOR]

Background: The Score Committee of the European Foot and Ankle Society (EFAS) developed, validated, and published the EFAS Score in nine European languages (English, German, French, Italian, Polish, Dutch, Swedish, Finnish, Turkish). From other languages under validation, the Persian version finished data acquisition and underwent further validation.Methods: The Persian version of the EFAS Score was developed and validated in three stages: 1) item (question) identification (completed during initial validation study), 2) item reduction and scale exploration (completed during initial validation study), 3) confirmatory analyses and responsiveness of Persian version (completed during initial validation study in nine other languages). The data were collected pre-operatively and post-operatively at a minimum follow-up of 3 months and mean follow-up of 6 months. Item reduction, scale exploration, confirmatory analyses and responsiveness were executed using classical test theory and item response theory.Results: The internal consistency was confirmed in the Persian version (Cronbach's Alpha 0.82). The Standard Error of Measurement (SEM) was 0.38 and is similar to other language versions. Between baseline and follow-up, 97% of patients showed an improvement on their EFAS score, with excellent responsiveness (effect size 1.93).Conclusions: The Persian EFAS Score version was successfully validated in patients with a wide variety of foot and ankle pathologies. All score versions are freely available at www.efas.co. [ABSTRACT FROM AUTHOR]

In this study, we report the design and the synthesis of a Schiff base; Anil and its corresponding Boron Difluoride complexe; Boranil. The synthesis procedure was carried out adopting new, optimized reaction conditions. The Boranil dye presents the advantage to be emissive in solution. 1H and 19F NMR along with FTIR confirmed both compound's structure. To gain a better understanding of the solvatochromic behavior of Anil and Boranil, the dependence of the absorption spectra on the solvent's polarity was studied in depth. Thus, UV–Vis spectroscopy was performed in five selected solvents. In addition to the solvent's polarity effect, the influence of BF2 moiety introduction on the molecule's photophysical properties was also evaluated. When examining different absorption spectra, we found that the title fluorescent dye exhibited weak solvatochromic (11 nm in THF) as well as a slight redshift broader and relatively more structured absorption spectra after complexation. Besides, we investigate the obtained key structure–property relationships through DFT and TD‐DFT calculations using a 6–311++ G (d, p) basis set. Quantum chemical calculations allowed confirming proposed structures and understanding their electronic structure in larger details. Theoretical results also showed good agreement with the experimental findings. Finally, the frontier molecular orbitals were investigated to illustrate the pi‐conjugation and charge transfer effect. [ABSTRACT FROM AUTHOR]

Background: The Score Committee of the European Foot and Ankle Society (EFAS) developed, validated, and published the EFAS Score in seven European languages (English, German, French, Italian, Polish, Dutch, Swedish). From other languages under validation, the Finnish and Turkish versions finished data acquisition and underwent further validation.Methods: The EFAS Score was developed and validated in three stages: 1) item (question) identification (completed during initial validation study), 2) item reduction and scale exploration (completed during initial validation study), 3) confirmatory analyses and responsiveness of Finnish and Turkish version (completed during initial validation study in seven other languages). The data were collected pre-operatively and post-operatively at a minimum follow-up of 3 months and mean follow-up of 6 months. Item reduction, scale exploration, confirmatory analyses and responsiveness were executed using classical test theory and item response theory.Results: The internal consistency of the scale was confirmed in the Finnish and Turkish versions (Cronbach's Alpha >0.8). Responsiveness was good, with moderate to large effect sizes in both languages, and evidence of a statistically significant positive association between the EFAS Score and patient-reported improvement.Conclusions: The Finnish and Turkish EFAS Score versions were successfully validated in the orthopaedic ankle and foot surgery patients, including a wide variety of foot and ankle pathologies. All score versions are freely available at www.efas.co. [ABSTRACT FROM AUTHOR]

Background: Understanding the work habits, attitudes, and experiences of women physicians is critical for optimal patient care. In a gendered work environment, obstacles faced hinder women physicians from contributing to their full ability. This study investigated how women physicians' work habits are viewed, in the context of women's attitudes and experiences. Methods: An analysis of the medical literature (1990–2017) was undertaken. Published studies were located using search engines, article references, consultation with experts, and relevant Mesh terms. Of 1185 listings, 354 studies were evaluated and 44 articles, selected by three reviewers, were analyzed in detail. Results: Four themes emerged—practice styles, productivity, prevailing attitudes, and the workplace environment. Comparing women physicians to male colleagues as a standard for evaluating performance, for example, undervalues distinctive characteristics women bring to medical practice. Productivity models that focus on work hours, procedures, and publications do not encompass the full scope of patient care. Conclusions: Solutions offered mainly have been designed to help women physicians fit into existing workplace environments, but traditionally available "adapt or exit" options in response to challenges faced appear insufficient. A gender equity perspective helps to explain findings and suggests ways to reshape the health care workplace to better understand, utilize, and retain women physicians. [ABSTRACT FROM AUTHOR]

In the Swedish news-press, loneliness among older people is presented as a severe problem that needs to be solved. The issue of who is responsible for reducing loneliness and how this responsibility is designated is, however, rarely discussed. In this study, we have analysed how responsibility is designated and constructed in articles from the Swedish news-press. Focus has been on identifying responsibility in discourses proceeding from the concept of subject positions. This concept has enabled analysis on how responsibility is negotiated and who is positioned as a responsible actor with the ability to perform actions that reduce loneliness. Three dominating discourses were found. In the discourse of responsibility within politics and the welfare state , the responsibility is both self-taken and designated to other institutions held responsible for not initiating sufficient measures to reduce loneliness. In the discourse of responsibility within societal and evolutionary perspectives on loneliness , developments beyond the individual's control are considered to contribute to loneliness. At the same time 'we' in 'society' are considered capable of reducing loneliness, thereby constructing individuals as responsible actors. Within the discourses of responsibility within senior organisations , both senior organisations and people who participate in activities are constructed as responsible actors. In conclusion, the responsibility for reducing loneliness is, apart from the discourse on senior organisations, designated to those working with older people. [ABSTRACT FROM AUTHOR]

Mental imagery is used by most people in their day-to-day cognition, for example, in planning, daydreaming, or remembering. Importantly, mental imagery has a powerful influence on emotion and is critically involved in many mental disorders. Thus, understanding the link between mental imagery and emotion is of clinical interest. For example, exposure therapy can be successfully conducted using mental imagery of fear-provoking stimuli, i.e., imaginal exposure. In this vein, accumulating evidence shows that mental imagery of a fearful stimulus produces a similar physiological and neural response as actual perception of the stimulus. Alas, knowledge of the neural processes underlying the link between mental imagery and emotion is limited. Functional magnetic resonance imaging data from a previous study on imaginal exposure (N = 30) was used to examine the functional connectivity during the production of phobic and neutral mental imagery. Regions of interest were selected from meta-analyses on brain regions consistently recruited during mental imagery production and phobic fear, respectively. Results showed that these regions were positively correlated during both phobic and neutral mental imagery production. Very few differences in functional connectivity between phobic and neutral imagery were found. Specifically, weaker functional connectivity between the supplemental motor area and a region including parts of the left insula and inferior frontal gyrus was observed during phobic (vs neutral) imagery. In conclusion, our findings suggest that brain regions previously implicated in mental imagery production and phobic fear are highly interconnected during the production of both phobic and neutral imagery. • Mental imagery and fear-related brain areas show extensive functional connectivity. • Functional connectivity is similar during phobic and neutral mental imagery. • Amygdala connectivity did not differ between phobic and neutral mental imagery. [ABSTRACT FROM AUTHOR]

Investigates the Cotton-Mouton effect of liquid water where the liquid is represented by semi-continuum model. Details on semi-continuum model; Role of atomic orbitals in obtaining gauge-origin independent calculations; Analysis on the short-range interactions between water molecules.

Background: A scientifically sound validated foot and ankle specific score validated ab initio for different languages is missing. The aim of a project of the European Foot and Ankle Society (EFAS) was to develop, validate, and publish a new score(the EFAS-Score) for different European languages.Methods: The EFAS Score was developed and validated in three stages: (1) item (question) identification, (2) item reduction and scale exploration, (3) confirmatory analyses and responsiveness. The following score specifications were chosen: scale/subscale (Likert 0-4), questionnaire based, outcome measure, patient related outcome measurement. For stage 3, data were collected pre-operatively and at a minimum follow-up of 3 months and mean follow-up of 6 months. Item reduction, scale exploration, confirmatory analyses and responsiveness were executed using analyses from classical test theory and item response theory.Results: Stage 1 resulted in 31 general and 7 sports related questions. In stage 2, a 6-item general EFAS Score was constructed using English, German, French and Swedish language data. In stage 3, internal consistency of the scale was confirmed in seven languages: the original four languages, plus Dutch, Italian and Polish (Cronbach's Alpha >0.86 in all language versions). Responsiveness was good, with moderate to large effect sizes in all languages, and significant positive association between the EFAS Score and patient-reported improvement. No sound EFAS Sports Score could be constructed.Conclusions: The multi-language EFAS Score was successfully validated in the orthopaedic ankle and foot surgery patient population, including a wide variety of foot and ankle pathologies. All score versions are freely available at www.efas.co. [ABSTRACT FROM AUTHOR]

• A magnetically modified nanocellulose have been introduced as a nano-catalyst. • The photophysical properties of syntesized Imidazoles have been studied. • The multi-substituted Imidazoles have been used as chemosensors for cation metals. In this contribution, we report the design of magnetic functionalized nanocellulose by an in-Situ approach. The fabricated polymer matrix was utilized as an efficient heterogeneous catalyst for one-pot multi-component synthesis of fluorescent multi-substituted imidazoles under green optimized conditions. The eco-friendly protocol afforded, short reaction times, excellent yields and catalyst easy recycling through magnetic recovery. The geometric optimization, MEP and FMOs have also been carried out at B3LYP‐D3/6–311++ G (d, p) level of Density Functional Theory simulations in ethanol to elucidate the substituent's effect on molecule's planarity, surface studies, their electronic structure as well as their intermolecular charge transfer. Furthermore, the synthesized multi-substituted Imidazole derivatives exhibited remarkable fluorescent properties explored in cation metal's chromogenic and fluorogenic detection. [Display omitted] [ABSTRACT FROM AUTHOR]

Memories can be modified when recalled. Experimental fear conditioning studies support that amygdala-localized fear memories are attenuated when reconsolidation is disrupted through extinction training immediately following memory activation. Recently, using functional brain imaging in individuals with lifelong spider fears, we demonstrated that fear memory activation followed by repeated exposure to feared cues after 10 min, thereby disrupting reconsolidation, attenuated activity in the amygdala during later re-exposure, and also facilitated approach behavior to feared cues. In contrast, repeated exposure 6 h after fear memory activation, allowing for reconsolidation, did not attenuate amygdala activity and resulted in less approach behavior as compared to the group that received disrupted reconsolidation. We here evaluated if these effects are stable after 6 months and found that amygdala activity was further reduced in both groups, with a tendency towards greater reductions in the 10 min than the 6 h group. Hence, disrupted reconsolidation results in long lasting attenuation of amygdala activity. The behavioral effect, with more approach towards previously feared cues, in the 10 min than the 6 h group also persisted. Thus, the brain effect of disrupted reconsolidation is stable over 6 months and the behavioral effect also remained. We therefore conclude that disrupted reconsolidation result in a long-lasting diminished fear memory representation in the amygdala which may have clinical importance. [ABSTRACT FROM AUTHOR]

Loneliness among older people is an issue that engages the general public and various professions and organizations in contemporary Swedish society. One public arena where this engagement is particularly evident is within the Swedish news-press, where articles on loneliness among older people are frequently published. Loneliness is commonly perceived as significantly related to ageing and older people. In addition, the mass media is considered to have a crucial influence in shaping general perceptions of older people. The aim of this study is to examine how loneliness among older people is constructed in the Swedish news-press and whether there is a prevailing “loneliness discourse” within this context. The empirical material consists of 94 articles from the Swedish news-press from the years 2013–2014. Two dominating discourses was found. Loneliness — within the discourse of eldercare, politics and the welfare society , is primarily written about in news articles and debate articles by a variety of authors, such as politicians and representatives from organizations. Within this discourse, loneliness is utilized as a concept to motivate the need for political change and the allocations of resources and to amplify deficiencies within eldercare, politics and the welfare society . The second discourse, Loneliness — within the discourse of volunteer work , is addressed in reportage articles written by journalists. In this discourse focus was on depicting volunteers and enhancing the importance of volunteer work . Here, loneliness serves as a motive for performing volunteer work. In addition, the discourse of Research reports on older people's health was found, although less significant compared to the two major discourses. Within this discourse ageing is presented as a risk, where loneliness is one of these risk factors. Despite some minor differences, loneliness, within all three discourses, is given the meaning of being a problem that needs to be solved. A central finding in this study is that focus in the articles, from Swedish news-press, is not mainly on loneliness but rather on eldercare, politics and the welfare state, volunteer work and health among older people. Loneliness is, consequently, used as a concept to motivate the need for political change and the allocation of resources for older people, to enhance the values of volunteer work and to emphasize the risks associated with ageing. [ABSTRACT FROM AUTHOR]

Memories are not set forever, but can be altered following reactivation, which renders memories malleable, before they are again stabilized through reconsolidation. Fear memories can be attenuated by using extinction during the malleable period. The present study adopts a novel form of extinction, using verbal instructions, in order to examine whether fear memory reconsolidation can be affected by an imaginal exposure. The extinction using verbal instructions, called imaginal extinction, consists of a recorded voice encouraging participants to imagine the scene in which fear was acquired, and to envision the stimuli before their inner eye. The voice signals stimuli appearance, and identical to standard (in vivo) extinction, participants discover that the conditioned stimulus no longer is followed by unconditioned stimulus (UCS). In this way, imaginal extinction translates clinically used imaginal exposure into the standard experimental fear conditioning paradigm. Fear was acquired by pairing pictorial stimuli with an electric shock UCS. Then, both standard and imaginal extinction were given following fear memory reactivation, either after 10 min, within the reconsolidation interval, or after 6 h, outside of the reconsolidation interval. In vivo and imaginal extinction produced comparable reductions in conditioned responses during extinction and importantly, both disrupted reconsolidation of conditioned fear and abolished stimulus discrimination between reinforced and non-reinforced cues. Thus, disrupted reconsolidation of fear conditioning can be achieved without in vivo stimulus presentation, through purely cognitive means, suggesting possible therapeutic applications. [ABSTRACT FROM AUTHOR]

Summary Memories become labile and malleable to modification when recalled [ 1 ]. Fear-conditioning experiments in both rodents and humans indicate that amygdala-localized short-term fear memories can be attenuated by disruption of their reconsolidation with extinction training soon after memory activation [ 2–7 ]. However, this may not be true for natural long-term fears. Studies in rodents indicate that although it is possible to disrupt the reconsolidation of older memories [ 8–11 ], they appear to be more resistant [ 1, 3, 9, 12, 13 ]. In humans, 1-week-old conditioned fear memories have been attenuated by behaviorally induced disruption of reconsolidation [ 14 ], but it remains to be seen whether this is possible for naturally occurring long-term fears and whether the underlying neural mechanisms are similar to those found in experimental fear-conditioning paradigms. Using functional brain imaging in individuals with a lifelong fear of spiders, we show that fear memory activation followed by repeated exposure to feared cues after 10 min, which disrupts reconsolidation, attenuates activity in the basolateral amygdala at re-exposure 24 hr later. In contrast, repeated exposure 6 hr after fear memory activation, which allows for reconsolidation, did not attenuate amygdala activity. Disrupted, but not undisrupted, reconsolidation facilitated approach behavior to feared cues, and approach behavior was inversely related to amygdala activity during re-exposure. We conclude that memory activation immediately preceding exposure attenuates the neural and behavioral expression of decades-old fear memories and that, similar to experimentally induced fear memories, the basolateral amygdala is crucially involved in this process. [ABSTRACT FROM AUTHOR]

To characterize infections and their management in oncology patients at the end of life, we conducted a review of the literature. Eight studies assessing infection in 957 patients with various malignancies were identified. Forty-two percent of terminally ill patients developed infections in the final phase of care. The greatest frequency of treatment with antibiotics occurred in acute care hospitals. Enterobacteriaceae and S. aureus were the most frequently isolated bacteria, and urinary and respiratory tracts the most frequently involved sites of infection. A total of 19-39% of individuals with suspected infection and advanced cancer died. The decision whether to treat or not in the palliative care setting may be complex and requires an individualized approach. Further research in this area will help develop a consensus for management that will facilitate education of students and residents regarding complex decisions of care of infections at the end of life. [ABSTRACT FROM AUTHOR]

In this work, we investigated in detail the upconversion properties of several types of nanoparticles, including NaYF4:5%Yb3+/30%Mn2+, NaYF4:40%Mn2+/x%Yb3+ (x% = 1, 5, 10, 20, 30, and 40), NaYF4:2%Er3+/x%Mn2+ (x% = 20, 30, 40, 50, 60, and 70), NaYF4:40%Mn2+/x%Er3+ (x% = 1, 2, 5, and 10), and NaYF4:40%Mn2+/1%Yb3+/x%Er3+ (x% = 0, 2, 5, and 10). We studied their upconversion emission under 980 nm excitation in both pulsed and continuous wave modes at different synthesis temperatures. The nanoparticles were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), and photoluminescence (PL) spectroscopy. The doping of Yb3+ and Mn2+ ions resulted in the nanoparticles assuming cubic and hexagonal crystal structures. The emission intensity increased (106.4 (a.u.*103) to 334.4(a.u.*103)) with increasing synthesis temperature from 120 to 140 °C, while a sharp decrease was observed when the synthesis temperature was increased to 200 °C. The gradual decrease in peak intensity with increasing Mn2+ concentration from 20 to 70% was attributed to energy transfer from Mn2+ to Yb3+. In NaYF4:Mn2+/Yb3+/Er3+ UCNPs, increasing the Er3+ concentration from 0 to 10% led to the disappearance of the blue, orange, and green emission bands. The intense upconversion luminescence pattern with high spatial resolution indicates excellent potential for applications in displays, biological sensors, photodetectors, and solar energy converters. [ABSTRACT FROM AUTHOR]

Fear memories can be attenuated by reactivation followed by disrupted reconsolidation. Using functional magnetic resonance imaging we recently showed that reactivation and reconsolidation of a conditioned fear memory trace in the basolateral amygdala predicts subsequent fear expression over two days, while reactivation followed by disrupted reconsolidation abolishes the memory trace and suppresses fear. In this follow-up study we demonstrate that the behavioral effect persists over 18 months reflected in superior reacquisition after undisrupted, as compared to disrupted reconsolidation, and that neural activity in the basolateral amygdala representing the initial fear memory predicts return of fear. We conclude that disrupting reconsolidation have long lasting behavioral effects and may permanently erase the fear component of an amygdala-dependent memory. [ABSTRACT FROM AUTHOR]

Highlights: [•] The literature on human reconsolidation is reviewed and discussed. [•] Methods of memory reactivation to induce reconsolidation are discussed. [•] The rationale behind the clinical interest of reconsolidation studies is discussed. [Copyright &y& Elsevier]

Genome-scale metabolic models ( GEMs) have proven useful as scaffolds for the integration of omics data for understanding the genotype-phenotype relationship in a mechanistic manner. Here, we evaluated the presence/absence of proteins encoded by 15,841 genes in 27 hepatocellular carcinoma (HCC) patients using immunohistochemistry. We used this information to reconstruct personalized GEMs for six HCC patients based on the proteomics data, HMR 2.0, and a task-driven model reconstruction algorithm ( tINIT). The personalized GEMs were employed to identify anticancer drugs using the concept of antimetabolites; i.e., drugs that are structural analogs to metabolites. The toxicity of each antimetabolite was predicted by assessing the in silico functionality of 83 healthy cell type-specific GEMs, which were also reconstructed with the tINIT algorithm. We predicted 101 antimetabolites that could be effective in preventing tumor growth in all HCC patients, and 46 antimetabolites which were specific to individual patients. Twenty-two of the 101 predicted antimetabolites have already been used in different cancer treatment strategies, while the remaining antimetabolites represent new potential drugs. Finally, one of the identified targets was validated experimentally, and it was confirmed to attenuate growth of the HepG2 cell line. [ABSTRACT FROM AUTHOR]

Background: We conducted a prospective, randomized, controlled multicenter trial to compare operative with nonoperative treatment of displaced intra-articular calcaneal fractures.Methods: Eighty-two patients who presented to five trauma centers from 1994 to 1998 with an intra-articular calcaneal fracture with ≥2 mm of displacement (as verified by computed tomography) were randomized to operative or nonoperative treatment. Independent observers followed the two groups radiographically and clinically at one year and eight to twelve years. The primary outcome measures were a visual analog scale (VAS) for pain and function and the self-administrated Short Form (SF)-36 general health outcome questionnaire. The secondary outcome measures were residual pain evaluated with a VAS, the American Orthopaedic Foot & Ankle Society (AOFAS) scale, and the Olerud-Molander (OM) scale.Results: Forty-two patients in the operative treatment group and forty in the nonoperative group were included. The two groups were comparable with respect to age, sex, and fracture types. Seventy-six patients were available for follow-up at one year and fifty-eight at eight to twelve years. The primary and secondary outcome measures did not differ significantly between the two treatment groups at one year of follow-up. At eight to twelve years of follow-up, there was a trend toward better scores on the patient-reported primary VAS score for pain and function (p = 0.07) and the physical component of the SF-36 (p = 0.06) in the operative group. The prevalence of radiographically evident posttraumatic subtalar arthritis was lower in the operative group (risk reduction, 41%).Conclusions: Operative treatment was not superior in managing displaced intra-articular calcaneal fractures at one year of follow-up but appeared to have some benefits at eight to twelve years. Operative treatment was associated with a higher risk of complications but a reduced prevalence of posttraumatic arthritis evident on follow-up radiographs.Level Of Evidence: Therapeutic level II. See instructions for authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

In this work, we describe the application of a genome-scale metabolic model and flux balance analysis for the prediction of succinic acid overproduction strategies in Saccharomyces cerevisiae. The top three single gene deletion strategies, Δ mdh1, Δ oac1, and Δ dic1, were tested using knock-out strains cultivated anaerobically on glucose, coupled with physiological and DNA microarray characterization. While Δ mdh1 and Δ oac1 strains failed to produce succinate, Δ dic1 produced 0.02 C-mol/C-mol glucose, in close agreement with model predictions (0.03 C-mol/C-mol glucose). Transcriptional profiling suggests that succinate formation is coupled to mitochondrial redox balancing, and more specifically, reductive TCA cycle activity. While far from industrial titers, this proof-of-concept suggests that in silico predictions coupled with experimental validation can be used to identify novel and non-intuitive metabolic engineering strategies. [ABSTRACT FROM AUTHOR]

We present the RAVEN (Reconstruction, Analysis and Visualization of Metabolic Networks) Toolbox: a software suite that allows for semi-automated reconstruction of genome-scale models. It makes use of published models and/or the KEGG database, coupled with extensive gap-filling and quality control features. The software suite also contains methods for visualizing simulation results and omics data, as well as a range of methods for performing simulations and analyzing the results. The software is a useful tool for system-wide data analysis in a metabolic context and for streamlined reconstruction of metabolic networks based on protein homology. The RAVEN Toolbox workflow was applied in order to reconstruct a genome-scale metabolic model for the important microbial cell factory Penicillium chrysogenum Wisconsin54-1255. The model was validated in a bibliomic study of in total 440 references, and it comprises 1471 unique biochemical reactions and 1006 ORFs. It was then used to study the roles of ATP and NADPH in the biosynthesis of penicillin, and to identify potential metabolic engineering targets for maximization of penicillin production. [ABSTRACT FROM AUTHOR]

We evaluated the presence/absence of proteins encoded by 14 077 genes in adipocytes obtained from different tissue samples using immunohistochemistry. By combining this with previously published adipocyte-specific proteome data, we identified proteins associated with 7340 genes in human adipocytes. This information was used to reconstruct a comprehensive and functional genome-scale metabolic model of adipocyte metabolism. The resulting metabolic model, iAdipocytes1809, enables mechanistic insights into adipocyte metabolism on a genome-wide level, and can serve as a scaffold for integration of omics data to understand the genotype–phenotype relationship in obese subjects. By integrating human transcriptome and fluxome data, we found an increase in the metabolic activity around androsterone, ganglioside GM2 and degradation products of heparan sulfate and keratan sulfate, and a decrease in mitochondrial metabolic activities in obese subjects compared with lean subjects. Our study hereby shows a path to identify new therapeutic targets for treating obesity through combination of high throughput patient data and metabolic modeling. [ABSTRACT FROM AUTHOR]

Development of high throughput analytical methods has given physicians the potential access to extensive and patientspecific data sets, such as gene sequences, gene expression profiles or metabolite footprints. This opens for a new approach in health care, which is both personalized and based on system-level analysis. Genome-scale metabolic networks provide a mechanistic description of the relationships between different genes, which is valuable for the analysis and interpretation of large experimental data-sets. Here we describe the generation of genome-scale active metabolic networks for 69 different cell types and 16 cancer types using the INIT (Integrative Network Inference for Tissues) algorithm. The INIT algorithm uses cell type specific information about protein abundances contained in the Human Proteome Atlas as the main source of evidence. The generated models constitute the first step towards establishing a Human Metabolic Atlas, which will be a comprehensive description (accessible online) of the metabolism of different human cell types, and will allow for tissue-level and organism-level simulations in order to achieve a better understanding of complex diseases. A comparative analysis between the active metabolic networks of cancer types and healthy cell types allowed for identification of cancer-specific metabolic features that constitute generic potential drug targets for cancer treatment. [ABSTRACT FROM AUTHOR]

Genome-scale metabolic models are available for an increasing number of organisms and can be used to define the region of feasible metabolic flux distributions. In this work we use as constraints a small set of experimental metabolic fluxes, which reduces the region of feasible metabolic states. Once the region of feasible flux distributions has been defined, a set of possible flux distributions is obtained by random sampling and the averages and standard deviations for each of the metabolic fluxes in the genome-scale model are calculated. These values allow estimation of the significance of change for each reaction rate between different conditions and comparison of it with the significance of change in gene transcription for the corresponding enzymes. The comparison of flux change and gene expression allows identification of enzymes showing a significant correlation between flux change and expression change (transcriptional regulation) as well as reactions whose flux change is likely to be driven only by changes in the metabolite concentrations (metabolic regulation). The changes due to growth on four different carbon sources and as a consequence of five gene deletions were analyzed for Saccharomyces cerevisiae. The enzymes with transcriptional regulation showed enrichment in certain transcription factors. This has not been previously reported. The information provided by the presented method could guide the discovery of new metabolic engineering strategies or the identification of drug targets for treatment of metabolic diseases. [ABSTRACT FROM AUTHOR]

Abstract: The exploitation of microorganisms in industrial, medical, food and environmental biotechnology requires a comprehensive understanding of their physiology. The availability of genome sequences and accumulation of high-throughput data allows gaining understanding of microbial physiology at the systems level, and genome-scale metabolic models represent a valuable framework for integrative analysis of metabolism of microorganisms. Genome-scale metabolic models are reconstructed based on a combination of genome sequence information and detailed biochemical information, and these reconstructed models can be used for analyzing and simulating the operation of metabolism in response to different stimuli. Here we discuss the requirement for having detailed physiological insight in order to exploit microorganisms for production of fuels, chemicals and pharmaceuticals. We further describe the reconstruction process of genome-scale metabolic models and different algorithms that can be used to apply these models to gain improved insight into microbial physiology. [Copyright &y& Elsevier]

Loss of water through the immature skin can lead to hypothermia and dehydration in preterm infants. The water and glycerol channel aquaglyceroporin-3 (AQP3) is abundant in fetal epidermis and might influence epidermal water handling and transepidermal water flux around birth. To investigate the role of AQP3 in immature skin, we measured in vivo transepidermal water transport and AQP3 expression in rat pups exposed to clinically relevant fluid homeostasis perturbations. Preterm (E18) rat pups were studied after antenatal corticosteroid exposure (ANS), and neonatal (P1) rat pups after an 18 h fast. Transepidermal water loss (TEWL) and skin hydration were determined, AQP3 mRNA was quantified by RT-PCR, and in-situ hybridization and immunocytochemistry were applied to map AQP3 expression. ANS resulted in an improved skin barrier (lower TEWL and skin hydration), while AQP3 mRNA and protein increased. Fasting led to loss of barrier integrity along with an increase in skin hydration. These alterations were not paralleled by any changes in AQP3. To conclude, antenatal corticosteroids and early postnatal fluid restriction produce differential effects on skin barrier function and epidermal AQP3 expression in the rat. In perinatal rats, AQP3 does not directly determine net water transport through the skin. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the utility and content validity of the Swedish version of the Volitional Questionnaire (VQ-S). The participants in this study were thirteen occupational therapists selected because they worked with clients for whom the VQ-S is appropriate (in this case, adults with intellectual impairments) and because they had knowledge of the Model of Human Occupation. These participants completed a demographic questionnaire at the beginning of the study. Each therapist then used the VQ-S a total of six times and after each time they completed a questionnaire concerning the utility and content validity of the instrument. After having administered the instrument six times they completed a third questionnaire that assessed their perceptions of the VQ-S based on their total experience. Data from these questionnaires and the six assessment forms with the actual client ratings were analyzed using both quantitative and qualitative procedures. The findings indicate that the VQ-S has clinical relevance and potential for implementation with adults with intellectual impairments. They also support the content validity of the VQ-S. [ABSTRACT FROM AUTHOR]