[Evidence-based practice in Bachelor of Nursing programmes in Austria, Germany, and Switzerland: A survey of general conditions, teaching content and methods]. / Evidenzbasierte Praxis in Bachelor-Pflegestudiengängen in Österreich, Deutschland und der Schweiz: ein Survey zu Rahmenbedingungen, Lehrinhalten und -methoden.

BACKGROUND/AIM: Evidence-based practice (EBP) provides an important basis for improving both the quality of care and patient safety. Formulating a research question, searching the literature, and critical appraisal are crucial to developing evidence-based practice. The aim of this survey was to provide an overview of how these topics are integrated into bachelor's degree programs in nursing in Austria, Germany, and the German-speaking part of Switzerland. We also aimed to show how teachers implement these subjects and how they experience and assess the implementation. METHOD: We conducted an exploratory cross-sectional study using an online survey sent out to program directors and teaching staff of all 58 bachelor's degree programs in nursing in Austria, Germany and the German-speaking part of Switzerland. For data collection, a questionnaire was developed containing items on general teaching conditions, contents, and methods of evidence-based nursing practice, as well as on the estimated thematic interest of students. The data were analysed descriptively. RESULTS: The program directors returned 24 questionnaires (41%). Of 75 questionnaires forwarded to the faculty, 17 (23%) were received from nine programs. On average, 5.6 teaching units (SD 2.6) are used for formulating a research question, 10 teaching units (SD 4.1) for literature review, and 11.3 teaching units (SD 6.9) for critical appraisal. Half of the teaching staff indicated that linkages between education and nursing care practice have been established. The traditional teaching method of frontal teaching is used predominantly. Student interest in topics was rated as moderate by most teachers. CONCLUSIONS: Topics on evidence-based practice are an integral part of bachelor's degree programs in nursing in German-speaking countries. An increase in teaching units, active learning methods and the growing interconnection between education and practice could improve the acquisition of competencies and attitudes of students regarding EBP and further advance its implementation in practice.

Development of Potent Mcl-1 Inhibitors: Structural Investigations on Macrocycles Originating from a DNA-Encoded Chemical Library Screen.

Evasion of apoptosis is critical for the development and growth of tumors. The pro-survival protein myeloid cell leukemia 1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family, associated with tumor aggressiveness, poor survival, and drug resistance. Development of Mcl-1 inhibitors implies blocking of protein-protein interactions, generally requiring a lengthy optimization process of large, complex molecules. Herein, we describe the use of DNA-encoded chemical library synthesis and screening to directly generate complex, yet conformationally privileged macrocyclic hits that serve as Mcl-1 inhibitors. By applying a conceptual combination of conformational analysis and structure-based design in combination with a robust synthetic platform allowing rapid analoging, we optimized in vitro potency of a lead series into the low nanomolar regime. Additionally, we demonstrate fine-tuning of the physicochemical properties of the macrocyclic compounds, resulting in the identification of lead candidates 57/59 with a balanced profile, which are suitable for future development toward therapeutic use.

Development of clinical items to identify dysphagia in patients with dementia-An e-Delphi study.

AIM: To identify clinical observable items that can be used to identify dysphagia while observing a typical eating situation. DESIGN: A three-round e-Delphi survey. METHODS: An expert panel consisting of five nurses, eight speech language therapists and five physicians participated in this three-round e-Delphi survey from November 2022 to January 2023. Round 1 presented the results of a literature research conducted in September 2022 and an open question to the participants. The answers were analysed using the content analysis method. In the following rounds, the results were presented back to the participants with a request to rate them for usefulness. Means, standard deviations, ANOVA and Fisher's exact test were used to demonstrate the panel's opinion, level of agreement, demographic characteristics of the participants as well as differences between the professional groups in regard of the rating of the items. Methods and results are reported in accordance with the 'Guidance on Conducting and Reporting Delphi Studies' (CREDES). RESULTS: The content analysis initially generated 36 items suggested by the expert panel. Seven additional items were incorporated from the literature review. In rounds 2 and 3, a 4-point Likert scale was used to rate each item and to calculate the level of agreement. The predetermined level of agreement exceeded 70% for 23 items. CONCLUSION: Based on the expert opinions, it is possible for nurses to identify dysphagia in patients with dementia by using the determined 23 items while observing a typical eating situation. PATIENT OR PUBLIC CONTRIBUTIONS: The expert panel contributed to the creation of this study by participating in the Delphi rounds. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The 23 items determined in this e-Delphi study enable nurses to make dietary adjustments or consult other members of the multidisciplinary team based on available evidence, enabling complications to be avoided. IMPACT: What problem did the study address? This study provides evidence regarding the identification of dysphagia in patients with dementia by nurses. What were the main findings? Twenty-three items were determined by an expert panel that can be used by nurses to identify dysphagia in patients with dementia while observing a typical eating situation. Where and on whom will the research have an impact? This research will have an impact on patients with dementia and the nurses caring for them. REPORTING METHOD: Methods and results are reported in accordance with the 'Guidance on Conducting and Reporting Delphi Studies' (CREDES) (Jünger et al., 2017), which promotes consistency and quality in conducting Delphi studies.

Resources and resilience factors: How advanced practice nurses can promote resilience in hearing and visually impaired people - A grounded theory perspective from Switzerland.

BACKGROUND: There is an increase in hearing and visual impairments worldwide. Those affected have a reduced ability to participate in social contacts, mobility, and access to information. Until now, there have been no recommendations for Advanced Practice Nurses (APNs) in Switzerland to support this group of people in the autonomous organization of everyday life in their own homes. OBJECTIVE: The aim of the study was to understand how people integrate their dual hearing and visual impairments into everyday life to derive recommendations for APNs to support individuals to manage their daily lives. METHODS: Following the constructivist approach of grounded theory, guided interviews and a questionnaire survey with hearing and visually impaired persons (n = 46) over 70 years of age on independent daily living were conducted (concurrent embedded strategy). In addition, demographic data on age, gender, living situation, and use of assistive devices were analyzed. FINDINGS: Based on the results, a communication-based dynamic resilience model (CoRes) was developed. This article represents the third phase of the three-stage-model. Integration of altered hearing depends on resources and risk factors. CONCLUSIONS: Advanced practice nurses can use recommendations from this research to actively help individuals and their families build resilience.

Self-gravitating clusters of Fermi-Dirac gas with planar, cylindrical, or spherical symmetry: Evolution of density profiles with temperature.

We calculate density profiles for self-gravitating clusters of an ideal Fermi-Dirac gas with nonrelativistic energy-momentum relation and macroscopic mass at thermal equilibrium. Our study includes clusters with planar symmetry in dimensions D=1,2,3, clusters with cylindrical symmetry in D=2,3, and clusters with spherical symmetry in D=3. Wall confinement is imposed where needed for stability against escape. The length scale and energy scale in use render all results independent of total mass and prove adequate at all temperatures. We present exact analytic expressions for (fully degenerate) T=0 density profiles in four of the six combinations of symmetry and dimensionality. Our numerical results for T>0 describe the emergence, upon quasistatic cooling, of a core with incipient degeneracy surrounded by a more dilute halo. The equilibrium macrostates are found to depend more strongly on the cluster symmetry than on the space dimensionality. We demonstrate the mechanical and thermal stability of spherical clusters with coexisting phases.

Free-energy landscapes and insertion pathways for peptides in membrane environment.

Free-energy landscapes for short peptides-specifically for variants of the pH low insertion peptide (pHLIP)-in the heterogeneous environment of a lipid bilayer or cell membrane are constructed, taking into account a set of dominant interactions and the conformational preferences of the peptide backbone. Our methodology interprets broken internal H-bonds along the backbone of a polypeptide as statistically interacting quasiparticles, activated from the helix reference state. The favored conformation depends on the local environment (ranging from polar to nonpolar), specifically on the availability of external H-bonds (with H_{2}O molecules or lipid headgroups) to replace internal H-bonds. The dominant side-chain contribution is accounted for by residue-specific transfer free energies between polar and nonpolar environments. The free-energy landscape is sensitive to the level of pH in the aqueous environment surrounding the membrane. For high pH, we identify pathways of descending free energy that suggest a coexistence of membrane-adsorbed peptides with peptides in solution. A drop in pH raises the degree of protonation of negatively charged residues and thus increases the hydrophobicity of peptide segments near the C terminus. For low pH, we identify insertion pathways between the membrane-adsorbed state and a stable trans-membrane state with the C terminus having crossed the membrane.

Mechanical response to tension and torque of molecular chains via statistically interacting particles associated with extension, contraction, twist, and supercoiling.

A methodology for the statistical mechanical analysis of polymeric chains under tension introduced previously is extended to include torque. The response of individual bonds between monomers or of entire groups of monomers to a combination of tension and torque involves, in the framework of this method of analysis, the (thermal or mechanical) activation of a specific mix of statistically interacting particles carrying quanta of extension or contraction and quanta of twist or supercoiling. The methodology, which is elucidated in applications of increasing complexity, is capable of describing the conversion between twist chirality and plectonemic chirality in quasistatic processes. The control variables are force or extension and torque or linkage (a combination of twist and writhe). The versatility of this approach is demonstrated in two applications relevant and promising for double-stranded DNA under controlled tension and torque. One application describes conformational transformations between (native) B-DNA, (underwound) S-DNA, and (overwound) P-DNA in accord with experimental data. The other application describes how the conversion between a twisted chain and a supercoiled chain accommodates variations of linkage and excess length in a buckling transition.

[Psychological Stress and its Consequences for the Cost of Illness: a Longitudinal Study in Germany]. / Psychische Belastung und ihre Folgen für die Krankheitskosten ­ eine Längsschnittstudie in Deutschland.

OBJECTIVE: The aim of this study was to examine the effects of mental illness on the level and composition of medical costs (outpatient costs, hospital costs, rehabilitation costs, drug costs) over time. METHOD: In a longitudinal design, we examined the psychological distress of 3,287 study participants from the adult general population using the Hospital Anxiety and Depression Scale (HADS) and its effect on the level and composition of medical costs resulting from mental illness in the year of survey t0 and the two subsequent years [t1] {t2}. RESULTS: Compared to the reference group with no mental distress, the cost of illness was significantly increased by a factor of 2.0 [2.2] {1.5} in the low mental distress group, by a factor of 3.7 [4.2] {3.1} in those with moderate mental distress, and by a factor of 7.5 [9.0] {5.2} in those with severe mental distress. Over time, significant effects on illness costs appeared only at the two outer edges of psychological distress levels (no and severe distress levels). As the level of mental distress increased, hospital costs dominated total costs due to mental distress and the proportion of outpatient medical costs in total costs decreased. CONCLUSIONS: The costs of illness rise steeply with the degree of mental stress. Preventing the progression of mental illness is therefore important not only from an individual but also from a health economic perspective.

Implementation and evaluation of an individualized physical exercise promotion program in people with manifested risk factors for multimorbidity (MultiPill-Exercise): a study protocol for a pragmatic randomized controlled trial.

BACKGROUND: Multimorbidity is a major problem in Europe, increasing the need for prevention and rehabilitation programs. In Germany no guidelines have been developed that focus on patients with multiple chronic non-communicable diseases (NCDs). Benefits of physical activity (PA) and exercise in NCDs have been proven, but most interventions focus on single conditions. The evaluation of the effectiveness, efficiency and safety of PA programs in patients suffering from multiple NCDs and the feasibility of the implementation within the health care service remain open research questions. METHODS: The multi-site randomized controlled pragmatic trial includes 320 sedentary subjects with at least two of the following NCDs, either manifested or in a pre-stage with evident risk factors: Cardio-vascular disease, Diabetes mellitus type 2, knee/ hip osteoarthritis and obesity. Participants will be recruited from general practitioners and medical specialists and randomized to standard care of a statutory health insurance or MultiPill-Exercise. Standard care includes a choice of one or a maximum of two 8- to 12-week health programs, including nutrition, exercise, relaxation or special disease management programs. MultiPill-Exercise is based on the bio-psycho-social health model, considering a person-oriented perspective in light of given individual characteristics and context factors. The 24-weeks intervention focuses on aerobic and strengthening exercises in line with the WHO PA recommendations. Psychological and pedagogical elements along with behavior change techniques are implemented to ease the initiation and maintenance of exercise participation and lifestyle change, including nutrition. Primary outcome will be short- and long-term PA measured with the European Health Interview Survey-Physical Activity Questionnaire (EHIS-PAQ). Secondly, the effectiveness of the program on generic, disease specific, economic, and exercise behavioral parameters, as well as program adherence and safety will be evaluated. DISCUSSION: Results of this trial evaluate the PA intervention program in people with multiple NCDs in a real-life scenario. It will serve as a proof of concept with the opportunity of translation into routine practice. This approach, as a multi-site RCT with its rigorous methods and standardized operating procedures for the conduction of the intervention, will allow valid conclusions for the implementation of PA interventions in people with multimorbidity. TRIAL REGISTRATION: The trial was registered at www.drks.de (ID: DRKS00025033 ) on 30th September 2021.

Calreticulin Shortage Results in Disturbance of Calcium Storage, Mitochondrial Disease, and Kidney Injury.

Renal Ca2+ reabsorption plays a central role in the fine-tuning of whole-body Ca2+ homeostasis. Here, we identified calreticulin (Calr) as a missing link in Ca2+ handling in the kidney and showed that a shortage of Calr results in mitochondrial disease and kidney pathogenesis. We demonstrated that Calr+/- mice displayed a chronic physiological low level of Calr and that this was associated with progressive renal injury manifested in glomerulosclerosis and tubulointerstitial damage. We found that Calr+/- kidney cells suffer from a disturbance in functionally active calcium stores and decrease in Ca2+ storage capacity. Consequently, the kidney cells displayed an abnormal activation of Ca2+ signaling and NF-κB pathways, resulting in inflammation and wide progressive kidney injury. Interestingly, the disturbance in the Ca2+ homeostasis and signaling in Calr+/- kidney mice cells triggered severe mitochondrial disease and aberrant mitophagy, resulting in a high level of oxidative stress and energy shortage. These findings provide novel mechanistic insight into the role of Calr in kidney calcium handling, function, and pathogenesis.

Self-gravitating clusters of Bose-Einstein gas with planar, cylindrical, or spherical symmetry: Gaseous density profiles and onset of condensation.

We calculate density profiles for self-gravitating clusters of an ideal Bose-Einstein gas with nonrelativistic energy-momentum relation and macroscopic mass at thermal equilibrium. Our study includes clusters with planar symmetry in dimensions D=1,2,3, clusters with cylindrical symmetry in D=2,3, and clusters with spherical symmetry in D=3. Wall confinement is imposed where needed to prevent escape. The length scale and energy scale in use for the gaseous phase render density profiles for gaseous macrostates independent of total mass. Density profiles for mixed-phase macrostates have a condensed core surrounded by a gaseous halo. The spatial extension of the core is negligibly small on the length scale tailored for the halo. The mechanical stability conditions as evident in caloric curves permit multiple macrostates to coexist. Their status regarding thermal equilibrium is examined by a comparison of free energies. The onset of condensation takes place at a nonzero temperature in all cases. The critical singularities and the nature of the phase transition vary with the symmetry of the cluster and the dimensionality of the space.

Media use in gynecological and obstetric care and women's perceived level of education received of lifestyle-related risks: A cross-sectional study.

OBJECTIVE: The application of media on lifestyle-related risk factors (LRRFs) by healthcare providers to educate women may improve women's adherence, health literacy, and awareness of LRRFs, as well as offspring's health outcomes. This study investigated whether exposure to media-based education in gynecological and obstetric care is associated with LRRFs perceived levels of education received during pregnancy and lactation. METHODS: We conducted a cross-sectional, observational study across 14 randomly generated sample points in the 12 most populated cities in Baden-Württemberg, southwest Germany. Women were recruited from gynecological and obstetric institutions. Participants were 219 women who met our inclusion criteria and completed the quantitative questionnaire. We applied ordinal logistic regression analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of women's perceived level of education received related to healthcare providers' exposure to media-based education. RESULTS: Media-based education on LRRFs during pregnancy through gynecologists and/or midwives were significantly associated with women's perceived level of education received (gynecologists: OR = 4.26 (95% CI: 2.04, 8.90; p < .001); midwives: OR = 3.86 (95% CI: 1.66, 8.98; p = .002)). Similar results were found for media-based education through gynecologists and/or midwives on LRRFs during lactation and its association with women's self-assessed level of perceived level of education received (gynecologists: OR = 4.76 (95% CI: 2.15, 10.56; p < .001); midwives: OR = 7.61 (95% CI: 3.13, 18.53; p < .001)). CONCLUSIONS: This study suggests that the exposure to media-based education in gynecological and obstetric care increases women's perceived level of education received of LRRFs during pregnancy and lactation. Therefore, it is recommendable to apply media in gynecological and obstetric care settings.

Jammed disks of two sizes and weights in a channel: Alternating sequences.

Disks of two sizes and weights in alternating sequence are confined to a long and narrow channel. The axis of the channel is horizontal and its plane vertical. The channel is closed off by pistons that freeze jammed microstates out of loose disk configurations subject to moderate pressure, gravity, and random agitations. Disk sizes and channel width are such that under jamming no disk remains loose and all disks touch one wall. We present exact results for the characterization of jammed macrostates including volume and entropy. The rigorous analysis divides the disk sequences of jammed microstates into overlapping tiles from which we construct a small number of species of statistically interacting particles. Jammed macrostates depend on dimensionless control parameters inferred from ratios between measures of expansion work against the pistons, gravitational potential energy, and intensity of random agitations. These control parameters enter the configurational statistics via the activation energies prior to jamming of the particles. The range of disk weights naturally divides into regimes where qualitatively different features come into play. We sketch a path toward generalizations that include random sequences under a modified jamming protocol.

The social and spiritual dimensions of parental experiences on end-of-life care of their child with cancer: A narrative review.

OBJECTIVE: Having a child with cancer is a burdensome experience for parents. Nurses need to better understand beliefs, hopes, and values of parents to holistically support them, which may have an impact on grief and depression. Thus, the aim of this paper was to highlight the social and spiritual dimensions of parental experiences on end-of-life care of their child with cancer. METHOD: A narrative literature review was conducted by systematically searching databases (CINAHL Complete, Academic Search Elite, MEDLINE) for relevant literature. The contents of included studies were critically appraised regarding their methodological quality. RESULTS: Eleven studies were included. In terms of the social dimension, three categories emerged that are important for parents: Being a Parent, Being in Relationship with the Child, and Being in Relationship with Health Professionals. Parents tried to maintain normality and joy for their child, but also kept control over the situation. They wanted to protect their child from suffering but also felt the need to talk to them about dying. Parents had ambivalent experiences with helpful but also burdensome staff. The spiritual dimension comprised two main categories, Hope and Faith and a Unique Bond. Hope was found to be an important source of strength, while Faith was only mentioned by some parents. For parents the emotional connection with their child constituted a source of meaning as well as a foundation, on which they based their decisions on. SIGNIFICANCE OF RESULTS: A therapeutic relationship and a supportive environment can be established by healthcare professionals by noticing, encouraging the unique bond between parents and their children, as well as by reflecting and addressing the parents' challenging situation.

Protein Phosphatases: A Neglected Target Family for Drug Discovery.

The gene family of protein phosphatases is a rich but under-exploited source of therapeutically validated drug targets modulating signal transduction pathways. Unlike the kinase family, research and development activities have not yet yielded any approved small-molecule drugs against a phosphatase. Approximately 20 years ago, the phosphatase family was classified as undruggable and intractable. This was primarily due to the spectacular failure of the cumulated industry-wide drug discovery efforts to develop PTP1B inhibitors. Recently, allosteric inhibitors against SHP2, a member of the phosphatase family, have entered clinical trails, which has reawakened industry's interest towards this neglected enzyme family. This contribution reviews the recent R&D trends around small-molecule efforts towards phosphatase modulators over the last years, rather than providing an exhaustive review of the field of allosteric phosphatase inhibitors.

["It's like being inside a capsule": How people aged 70 and over recognize and reflect on hearing and visual impairment - partial results from the KoRes stage model]. / "Es ist, wie in einer Kapsel zu sein." Wie Personen über 70 Jahren eine Hör- und Sehbeeinträchtigung erkennen und reflektieren - Teilergebnisse aus dem Stufenmodell KoRes.

INTRODUCTION: Combined hearing and vision impairment, which can negatively affect the performance of activities of daily living, is particularly prevalent in those over 70 years of age. Existing studies show that this dual sensory impairment has implications for safety in the home environment. Insights into how individuals integrate hearing and vision changes into their daily lives are needed for planning care-related interventions. METHODS: A qualitative method was used supplemented with quantitative methods ("Concurrent Embedded Strategy"). Based on the grounded theory approach, we conducted guided interviews with hearing- and vision-impaired individuals aged 70 years and over (n=46) as well as a questionnaire survey on how they cope with their daily lives. RESULTS: As part of their processing, individuals with hearing and visual impairments go through three stages that are closely linked to "being able to communicate." A partial result of the KoRes model is presented. This article focuses on the first two stages of this model: "diagnosis" and "reflection". CONCLUSION: People with dual sensory impairment behave reactively on the first two of a total of three stages with regard to the processing of their impairments. They need a supportive environment to be able to clarify these changes in hearing and vision and come to grips with the underlying causes.

Women's Media Use and Preferences of Media-Based Interventions on Lifestyle-Related Risk Factors in Gynecological and Obstetric Care: A Cross-Sectional Multi-Center Study in Germany.

This study aimed to investigate factors affecting (1) women's media use regarding health-related behaviors during pregnancy and lactation, (2) women's preferences for media format, and (3) the content of media-based interventions on lifestyle-related risk factors during pregnancy and lactation. A cross-sectional observational multi-center study of pregnant and lactating women and women of childbearing age was carried out in 14 randomly selected obstetric and gynecologic care settings in the 12 most populated cities in Baden-Wuerttemberg, South-West Germany. Data from 219 surveyed women showed that older women, pregnant women, and lactating women have a higher probability of using media during pregnancy and lactation, respectively. The majority of women preferred a combination of analog and digital media-based interventions in gynecological (46.9%) and obstetric (47.1%) care settings and at home (73.0%). Women would like to see information brochures and flyers on health-related behaviors during pregnancy and lactation for use in gynecological and obstetric care settings, and for media use at home, they would like to have books. The probability of preferring the favored media formats in gynecological and obstetric care settings and at home were associated with pregnancy status, relationship status, socioeconomic status (SES), ethnicity, and health insurance status. About 80% of the surveyed women preferred media content regarding recommendations for a healthy lifestyle and healthy behavior during pregnancy and lactation. All of the independent variables were associated with the probability of preferring a specific media content. The SES was found to play a major role in the probability of preferring a specific media content, followed by pregnancy status, ethnicity, and health insurance status. The results from our study provide a basis for tailored preventive interventions in gynecological and obstetric care settings and for use at home. The results imply that a woman can be reached before conception, during pregnancy, or during lactation with preventive measures tailored to their requirements; however, acceptance may vary across personal attributes, such as SES, ethnicity, and others.

Effectiveness of a mindfulness- and skill-based health-promoting leadership intervention on supervisor and employee levels: A quasi-experimental multisite field study.

Acknowledging increasing demands for workforce health, new theoretical concepts of health-oriented leadership (HoL) have been introduced, emphasizing the supervisor's direct and explicit engagement in workplace health by focusing on their self- and staff-care. However, empirical evidence of the effectiveness of HoL interventions for supervisors and their staff is still scarce. We developed a mindfulness- and skill-based HoL intervention and investigated its effectiveness in a quasi-experimental multisite field study including supervisor and employee ratings from 12 German companies. A total of n = 117 supervisors and their employees (n = 744) completed assessments on mental distress and perceived HoL before and after the intervention as well as during the 3-month follow-up period. The intervention group was compared to a passive control cohort based on propensity score matching. Hierarchical linear models showed that the supervisors who had participated in the HoL intervention experienced a significantly larger decrease in mental distress and an increase in health-oriented self-care as well as staff-care than did their matched controls (g = 0.18-0.59). These results were confirmed by intent-to-treat analyses. The effect on supervisors' mental distress was mediated by an increase of their health-oriented self-care and moderated by the frequency of their mindfulness practice. No significant effects appeared between groups regarding outcomes at the employee level. Overall, these findings indicate how HoL can be effectively trained to increase supervisors' self- and staff-care and reduce their mental distress. Future research should explore additional moderator variables, linkages to established work stress models, and improvements of these interventions to increase their effectiveness for employees. (PsycInfo Database Record (c) 2022 APA, all rights reserved).