A conserved peptide-binding pocket in HyNaC/ASIC ion channels.

The only known peptide-gated ion channels-FaNaCs/WaNaCs and HyNaCs-belong to different clades of the DEG/ENaC family. FaNaCs are activated by the short neuropeptide FMRFamide, and HyNaCs by Hydra RFamides, which are not evolutionarily related to FMRFamide. The FMRFamide-binding site in FaNaCs was recently identified in a cleft atop the large extracellular domain. However, this cleft is not conserved in HyNaCs. Here, we combined molecular modeling and site-directed mutagenesis and identified a putative binding pocket for Hydra-RFamides in the extracellular domain of the heterotrimeric HyNaC2/3/5. This pocket localizes to only one of the three subunit interfaces, indicating that this trimeric ion channel binds a single peptide ligand. We engineered an unnatural amino acid at the putative binding pocket entrance, which allowed covalent tethering of Hydra RFamide to the channel, thereby trapping the channel in an open conformation. The identified pocket localizes to the same region as the acidic pocket of acid-sensing ion channels (ASICs), which binds peptide ligands. The pocket in HyNaCs is less acidic, and both electrostatic and hydrophobic interactions contribute to peptide binding. Collectively, our results reveal a conserved ligand-binding pocket in HyNaCs and ASICs and indicate independent evolution of peptide-binding cavities in the two subgroups of peptide-gated ion channels.

Mitochondrial perturbation in the intestine causes microbiota-dependent injury and gene signatures discriminative of inflammatory disease.

Mitochondrial dysfunction is associated with inflammatory bowel diseases (IBDs). To understand how microbial-metabolic circuits contribute to intestinal injury, we disrupt mitochondrial function in the epithelium by deleting the mitochondrial chaperone, heat shock protein 60 (Hsp60Δ/ΔIEC). This metabolic perturbation causes self-resolving tissue injury. Regeneration is disrupted in the absence of the aryl hydrocarbon receptor (Hsp60Δ/ΔIEC;AhR-/-) involved in intestinal homeostasis or inflammatory regulator interleukin (IL)-10 (Hsp60Δ/ΔIEC;Il10-/-), causing IBD-like pathology. Injury is absent in the distal colon of germ-free (GF) Hsp60Δ/ΔIEC mice, highlighting bacterial control of metabolic injury. Colonizing GF Hsp60Δ/ΔIEC mice with the synthetic community OMM12 reveals expansion of metabolically flexible Bacteroides, and B. caecimuris mono-colonization recapitulates the injury. Transcriptional profiling of the metabolically impaired epithelium reveals gene signatures involved in oxidative stress (Ido1, Nos2, Duox2). These signatures are observed in samples from Crohn's disease patients, distinguishing active from inactive inflammation. Thus, mitochondrial perturbation of the epithelium causes microbiota-dependent injury with discriminative inflammatory gene profiles relevant for IBD.

Children's Perceptions and Experiences of Their Involvement in Their Parents' Mental Health Care - A Qualitative Literature Review.

This systematic review aims to synthesise the research on children's perceptions and experiences of their involvement in a parent's mental health care. After an extensive search and quality appraisal, 22 articles remained and were included in the review. The results show that children-although resourceful and with good intentions-frequently felt excluded. They hungered for information and felt their questions were abandoned. They also felt caught in a tumultuous life situation and struggled for support. Finally, they expressed the need to be seen and ultimately did not feel involved in their parent's mental health care.

Life situation of older people living with severe mental illness - A scoping review.

An increasing number of older people with severe mental illness (SMI) poses additional challenges to healthcare and social services. This scoping review aimed to investigate the life situation of older people living with severe mental illness and identify the research gaps in the existing literature. The current review followed the methodological framework for conducting scoping reviews by Arksey and O'Malley, consisting of five main stages: (1) identifying the research question (2) identifying relevant studies, (3) selecting the studies, (4) charting the data, and (5) collating, summarising, and reporting the results. An optional sixth stage, a consultation exercise, has also been used in this study: The scoping review was conducted in accordance with the PRISMA extension for scoping reviews PRISMA-ScR, and the databases PsychINFO Scopus, Cinahl, Web of Science and PubMed were used. A total of 24 studies were included in the review. The thematic analysis focused on: (1) the perspective of older people with SMI, (2) the perspective of healthcare professionals supporting older people with SMI, and (3) the perspective of informal carers supporting older people with SMI. The results describe the life situation of older people living with SMI, especially in relation to the older peoples' experiences of suffering and well-being. The staff and the informal carers need adequate knowledge to provide support to the older people with SMI. To gain greater knowledge about the life situation and support needed by older people with SMI, we strongly advocate additional research focusing on their own experiences.

"Good food equals good health": a focus group study of adolescent boys' perceptions of eating and weight.

BACKGROUND: Disordered eating refers to unhealthy, sometimes excessive eating including so-called compensatory behaviours such as extreme dieting or voluntary vomiting. Between 24% and 30% of adolescent boys are suggested to engage in disordered eating, making it a significant public health issue. However, current instruments for assessing disordered eating among adolescents have been primarily developed and validated for girls and women, which may make for flawed assessment of boys. The aim of this study is to shed light on adolescent boys' perceptions of eating, weight, and food intake to better understand their perspectives in service of disordered eating research. METHODS: This exploratory study was conducted from May to November 2022 using focus groups with a total of 39 adolescent boys (aged 12-19 years) who attended 7th to 12th grade in one of four schools in Southern Sweden. In addition, participants completed a form with questions on background demographics and eating habits. The transcripts of the focus group discussions were analysed using thematic analysis. RESULTS: The quantitative data showed that around one third of the adolescent boys were overweight or obese. They ate at least one meal per day with the family and ate healthy food about five days per week and unhealthy food about three. Analysis of the qualitative data yielded six themes: The intertwined relationship between food and one's health, "Don't worry, food makes you happy," "To be hungry or not. That is the question," Boys DO care about appearances, Dieting and weight gain, and Disordered eating is a tricky matter. CONCLUSION: Adolescent boys appeared to have a good understanding of food and healthy eating. They also experienced body positivity and seemed to have only minor issues regarding their weight. The primarily pathological perspective used to measure disordered eating among girls seems in need of revision to adhere to boys' thoughts and ideas regarding eating and weight.

Increasing taxonomic and functional characterization of host-microbiome interactions by DIA-PASEF metaproteomics.

Introduction: Metaproteomics is a rapidly advancing field that offers unique insights into the taxonomic composition and the functional activity of microbial communities, and their effects on host physiology. Classically, data-dependent acquisition (DDA) mass spectrometry (MS) has been applied for peptide identification and quantification in metaproteomics. However, DDA-MS exhibits well-known limitations in terms of depth, sensitivity, and reproducibility. Consequently, methodological improvements are required to better characterize the protein landscape of microbiomes and their interactions with the host. Methods: We present an optimized proteomic workflow that utilizes the information captured by Parallel Accumulation-Serial Fragmentation (PASEF) MS for comprehensive metaproteomic studies in complex fecal samples of mice. Results and discussion: We show that implementing PASEF using a DDA acquisition scheme (DDA-PASEF) increased peptide quantification up to 5 times and reached higher accuracy and reproducibility compared to previously published classical DDA and data-independent acquisition (DIA) methods. Furthermore, we demonstrate that the combination of DIA, PASEF, and neuronal-network-based data analysis, was superior to DDA-PASEF in all mentioned parameters. Importantly, DIA-PASEF expanded the dynamic range towards low-abundant proteins and it doubled the quantification of proteins with unknown or uncharacterized functions. Compared to previous classical DDA metaproteomic studies, DIA-PASEF resulted in the quantification of up to 4 times more taxonomic units using 16 times less injected peptides and 4 times shorter chromatography gradients. Moreover, 131 additional functional pathways distributed across more and even uniquely identified taxa were profiled as revealed by a peptide-centric taxonomic-functional analysis. We tested our workflow on a validated preclinical mouse model of neuropathic pain to assess longitudinal changes in host-gut microbiome interactions associated with pain - an unexplored topic for metaproteomics. We uncovered the significant enrichment of two bacterial classes upon pain, and, in addition, the upregulation of metabolic activities previously linked to chronic pain as well as various hitherto unknown ones. Furthermore, our data revealed pain-associated dynamics of proteome complexes implicated in the crosstalk between the host immune system and the gut microbiome. In conclusion, the DIA-PASEF metaproteomic workflow presented here provides a stepping stone towards a deeper understanding of microbial ecosystems across the breadth of biomedical and biotechnological fields.

Cultural diversity in health care teams: A systematic integrative review and research agenda.

BACKGROUND: Although team-based work is deemed key to improving the quality of national health care systems, adverse events related to teamwork account for up to one third of all incidents. Health care teams are typically multiprofessional and diverse in many aspects, but cultural diversity is one of the most challenging. PURPOSES: The objective of this review is to systematically analyze the literature to better understand the impact of cultural diversity in health care teams on team processes as well as team and patient outcomes. This study also explores the conditions that enable or hinder team functioning. METHODOLOGY: Through a systematic integrative literature review, this study builds on the input-process-output-context framework. Multiple searches of the main databases led to identifying 43 relevant articles. FINDINGS: The results suggest that, when not proactively managed, cultural diversity may have a negative effect on team communication and integration, increasing team conflict and thereby negatively influencing team performance, team climate, and patient safety, both directly and indirectly. Yet, when managed properly and in the presence of engaged and culturally sensitive leadership, cultural training, and open and transparent procedures, cultural diversity in health care teams can be an asset to health care organizations. Analyzing and aggregating these findings into an integrative framework, our study identifies several themes and a research agenda for future studies on culturally diverse health care teams. PRACTICE IMPLICATIONS: Our findings suggest that culturally diverse health care teams experience a number of challenges, pointing to the need for action or structures that enable these teams to perform better, such as emphasizing learning and allowing team members time to get to know each other outside work.

180° view on general practitioners' leadership skills: practice-level comparisons of leader and staff assessments using data from the cluster-randomised controlled IMPROVEjob study.

OBJECTIVES: Strong primary care leaders are needed to assure high quality services for patient populations. This study analysed general practitioners' (GP) leadership skills comparing practice-level self and staff assessments based on the full range of leadership model and the leader-member exchange (LMX). SETTING: The questionnaire survey was conducted among German general practice leaders and their staff participating in the IMPROVEjob trial. PARTICIPANTS: The study population comprised 60 German general practices with 366 participants: 84 GP practice leaders and 282 employees (28 physicians and 254 practice assistants). PRIMARY AND SECONDARY OUTCOME MEASURES: Leadership skills of the practice leaders were measured using the Integrative Leadership Questionnaire (German Fragebogen für integrative Führung) and the LMX-7 questionnaire. Leaders rated themselves and practice staff rated their leaders. The data was analysed by paired mean comparisons on the practice level. RESULTS: For most leadership dimensions, practice leaders rated themselves higher than their employees rated them. Differences were found for transformational leadership (p<0.001, d=0.41), especially for the dimensions 'innovation' (p<0.001, d=0.69) and 'individuality focus' (p<0.001, d=0.50). For transactional leadership, the dimension 'goal setting' differed significantly (p<0.01, d=0.30) but not the other dimensions. Scores for negative leadership were low and showed no differences between leaders and employees. Interestingly, employed physicians' rated their practice leaders higher on the two transformational ('performance development', 'providing a vision') and all transactional dimensions. The LMX-7 scale showed high quality relationships between leaders and employees. CONCLUSIONS: This 180° analysis of GPs' leadership skills with self and employee ratings indicated good relationships. There is a potential to improve leadership regarding goal-setting, innovation and focusing on individual team members. These results allow for the development of targeted interventions. TRIAL REGISTRATION NUMBER: German Clinical Trials Register, DRKS00012677. Registered 16 October 2019.

German GPs' Self-Perceived Role in the COVID-19 Pandemic: Leadership, Participation in Regional Services and Preferences for Future Pandemic Preparedness.

General practitioners (GPs) played a vital role during the COVID-19 pandemic. Little is known about GPs' view of their role, leadership, participation in regional services and preferences for future pandemic preparedness. This representative study of German GPs comprised a web-based survey and computer-assisted telephone interviewing (CATI). It addressed GPs' satisfaction with their role, self-perceived leadership (validated C-LEAD scale), participation in newly established health services, and preferences for future pandemic preparedness (net promotor score; NPS; range -100 to +100%). Statistical analyses were conducted using Spearman's correlation and Kruskal-Wallis tests. In total, 630 GPs completed the questionnaire and 102 GPs the CATI. In addition to their practice duties, most GPs (72.5%) participated in at least one regional health service, mainly vaccination centres/teams (52.7%). Self-perceived leadership was high with a C-LEAD score of 47.4 (max. 63; SD ± 8.5). Overall, 58.8% were not satisfied with their role which correlated with the feeling of being left alone (r = -0.349, p < 0.001). 77.5 % of respondents believed that political leaders underestimated GPs' potential contribution to pandemic control. Regarding regional pandemic services, GPs preferred COVID-19 focus practices (NPS +43.7) over diagnostic centres (NPS -31). Many GPs, though highly engaged regionally, were dissatisfied with their role but had clear preferences for future regional services. Future pandemic planning should integrate GPs' perspectives.

Experiences of primary care among young adults with mental illness - A systematic literature review.

BACKGROUND: Mental illness, such as depression, anxiety disorders, attention deficit hyperactivity disorder and different addictive diseases, has increased among young adults over the last decade. Mental illness is associated with distress and problems functioning in social activities. Healthcare centres, that is, primary care, serve as the first point of contact with healthcare professionals for those young adults and provide outpatient medical and nursing care covering both physical and mental illness. OBJECTIVE: To explore experiences of primary care among young adults with mental illness. METHODS: A systematic literature review was conducted that followed the method of Bettany-Saltikov and McSherry. A keyword search was performed in various databases, and after a quality assessment 23 articles were included in the review. RESULTS: Young adults' experiences from primary care are described in four categories - Facing difficulties to accept help, relational preconditions, structural and organisational hindrances and satisfaction with youth-focused mental health interventions. Young adults with mental illness experience many difficulties in accessing and receiving proper help from primary care. Further, they did not believe in recovery from mental illness, and they also expressed a lack of mental health literacy. CONCLUSION: While being the first contact with healthcare professionals, primary care needs to adjust its services to address the growing group of young adults suffering from mental illness. It is necessary to provide tailored guidelines and interventions in primary care for young adults with mental illness, and the Tidal Model may improve the contacts with young adults in primary care.

Adapting the pantograph limb: Differential robustness of fore- and hindlimb kinematics against genetically induced perturbation in the neural control networks and its evolutionary implications.

The evolutionary transformation of limb morphology to the four-segmented pantograph of therians is among the milestones of mammalian evolution. But, it is still unknown if changes of the mechanical limb function were accompanied by corresponding changes in development and sensorimotor control. The impressive locomotor performance of mammals leaves no doubt about the high integration of pattern formation, neural control and mechanics. But, deviations from normal intra- and interlimb coordination (spatial and temporal) become evident in the presence of perturbations. We induced a perturbation in the development of the neural circuits of the spinal cord of mice (Mus musculus) using a deletion of the Wilms tumor suppressor gene Wt1 in a subpopulation of dI6 interneurons. These interneurons are assumed to participate in the intermuscular coordination within the limb and in left-right-coordination between the limbs. We describe the locomotor kinematics in mice with conditional Wt1 knockout and compare them to mice without Wt1 deletion. Unlike knockout neonates, knockout adult mice do not display severe deviations from normal (=control group) interlimb coordination, but the coordinated protraction and retraction of the limbs is altered. The forelimbs are more affected by deviations from the control than the hindlimbs. This observation appears to reflect a different degree of integration and resistance against the induced perturbation between the limbs. Interestingly, the observed effects are similar to locomotor deficits reported to arise when sensory feedback from proprioceptors or cutaneous receptors is impaired. A putative participation of Wt1 positive dI6 interneurons in sensorimotor integration is therefore considered.

Phenotype- and species-specific skin proteomic signatures for incision-induced pain in humans and mice.

BACKGROUND: Acute pain after surgery is common and often leads to chronic post-surgical pain, but neither treatment nor prevention is currently sufficient. We hypothesised that specific protein networks (protein-protein interactions) are relevant for pain after surgery in humans and mice. METHODS: Standardised surgical incisions were performed in male human volunteers and male mice. Quantitative and qualitative sensory phenotyping were combined with unbiased quantitative mass spectrometry-based proteomics and protein network theory. The primary outcomes were skin protein signature changes in humans and phenotype-specific protein-protein interaction analysis 24 h after incision. Secondary outcomes were interspecies comparison of protein regulation as well as protein-protein interactions after incision and validation of selected proteins in human skin by immunofluorescence. RESULTS: Skin biopsies in 21 human volunteers revealed 119/1569 regulated proteins 24 h after incision. Protein-protein interaction analysis delineated remarkable differences between subjects with small (low responders, n=12) and large incision-related hyperalgesic areas (high responders, n=7), a phenotype most predictive of developing chronic post-surgical pain. Whereas low responders predominantly showed an anti-inflammatory protein signature, high responders exhibited signatures associated with a distinct proteolytic environment and persistent inflammation. Compared to humans, skin biopsies in mice habored even more regulated proteins (435/1871) 24 h after incision with limited overlap between species as assessed by proteome dynamics and PPI. Immunohistochemistry confirmed the expression of high priority candidates in human skin biopsies. CONCLUSIONS: Proteome profiling of human skin after incision revealed protein-protein interactions correlated with pain and hyperalgesia, which may be of potential significance for preventing chronic post-surgical pain. Importantly, protein-protein interactions were differentially modulated in mice compared to humans opening new avenues for successful translational research.

The role of sensory feedback from carpal sinus hairs in locomotor kinematics of rats (Rattus norvegicus, Rodentia) during walking on narrow substrates.

Carpal sinus hairs on the forearms are assumed to have evolved within the stem lineage of Theria. The presence and similar position of these specialized tactile hairs in scansorial and terrestrial species as well as earlier studies on rats indicate a biological role in sensing substrate irregularities in high structured environments to ensure the dynamic stability of the body during locomotion. While these sensors were considered as one functional unit until so far, the present study deals with the biological role of the single tactile hairs of the trident, assuming a role in sensing substrate diameters and adapting limb coordination and body posture to different arboreal inclinations. To investigate the influence of each hair, we studied the locomotion of rats on poles of two different diameters whereby we selectively removed individual carpal sinus hairs. The rats walked at speeds ranging from 0.12 m/s to 0.58 m/s. Normal-light high-speed cameras and x-ray fluoroscopy visualized the hairs and body dynamics during locomotion. The time lag between first contact of the hairs to the branch until contact of the forepaw was 56-108 ms. Within this time window the pronation/supination of the paw and anterior body posture are adjusted to the substrate diameter. We presume that the most proximal sinus hair (located between the medial and lateral one) senses the paw-substrate distance through the increasing bend from its first branch-contact until the contact of the paw. The medial and the lateral hairs touch the pole sides and thereby, may collect information about the properties of the small-diameter substrate. The removal of single hairs from the group results in minor changes of kinematic parameters, but locomotor stability is seriously impaired when more than one hair is cut. The kinematic responses span from a more crouched body posture and higher forearm pronation to paw slipping, muscle tremor or complete refusal to walk on the narrow substrate.

Deep proteome profiling reveals signatures of age and sex differences in paw skin and sciatic nerve of naïve mice.

The age and sex of studied animals profoundly impact experimental outcomes in biomedical research. However, most preclinical studies in mice use a wide-spanning age range from 4 to 20 weeks and do not assess male and female mice in parallel. This raises concerns regarding reproducibility and neglects potentially relevant age and sex differences, which are largely unknown at the molecular level in naïve mice. Here, we employed an optimized quantitative proteomics workflow in order to deeply profile mouse paw skin and sciatic nerves (SCN) - two tissues implicated in nociception and pain as well as diseases linked to inflammation, injury, and demyelination. Remarkably, we uncovered significant differences when comparing male and female mice at adolescent (4 weeks) and adult (14 weeks) age. Our analysis deciphered protein subsets and networks that were correlated with the age and/or sex of mice. Notably, among these were proteins/biological pathways with known (patho)physiological relevance, e.g., homeostasis and epidermal signaling in skin, and, in SCN, multiple myelin proteins and regulators of neuronal development. Extensive comparisons with available databases revealed that various proteins associated with distinct skin diseases and pain exhibited significant abundance changes in dependence on age and/or sex. Taken together, our study uncovers hitherto unknown sex and age differences at the level of proteins and protein networks. Overall, we provide a unique proteome resource that facilitates mechanistic insights into somatosensory and skin biology, and integrates age and sex as biological variables - a prerequisite for successful preclinical studies in mouse disease models.

Refractive Changes after Glaucoma Surgery-A Comparison between Trabeculectomy and XEN Microstent Implantation.

Best-corrected visual acuity often decreases temporarily or permanently after trabeculectomy (TE). The purpose of this study was to compare visual acuity and refractive changes after TE or XEN microstent implantation (XEN) in primary open-angle glaucoma (POAG) or pseudoexfoliation glaucoma (PEX) cases naïve to prior glaucoma surgery over a 24-month follow-up period. We analyzed 149 consecutive glaucoma patients who received either TE or XEN because of medically uncontrollable POAG or PEX. Intraocular pressure (IOP), IOP-lowering medication use, subjective and objective refraction and best-corrected visual acuity were evaluated. In addition, surgically induced astigmatism (SIA) was calculated and compared using the vector analysis method described by Jaffe and Clayman. A total of 93 eyes (85 POAG; 8 PEX) were treated with TE and 56 eyes (50 POAG; 6 PEX) with XEN. After 24 months, the mean IOP and number of IOP-lowering medications used decreased significantly after TE (p < 0.01) and XEN (p < 0.01). In the TE group, mean best-corrected visual acuity (BCVA) changed from 0.16 ± 0.26 to 0.23 ± 0.28 logMAR (p < 0.01) after 24 months, while mean BCVA did not change significantly in the XEN group (preoperative: 0.40 ± 0.50 logMAR, postoperative: 0.36 ± 0.49 logMAR; p = 0.28). SIA was almost the same in both groups at the end of the 24-month follow-up period (0.75 ± 0.60 diopters after TE and 0.81 ± 0.56 diopters after XEN; p = 0.57). In addition, there was no significant correlation between SIA and the observed BCVA changes or SIA and IOP reduction 12 or 24 months after TE or XEN. Our results demonstrate that TE and XEN are effective methods for reducing IOP and IOP-lowering medication use. The SIA was nearly similar in both groups. The SIA does not seem responsible for the decreased visual acuity after TE.

Two Year Functional and Structural Changes-A Comparison between Trabeculectomy and XEN Microstent Implantation Using Spectral Domain Optical Coherence Tomography.

The aim of this study was to analyze retinal nerve fiber layer (RNFL) thickness after trabeculectomy (TE) versus XEN microstent implantation (XEN) in primary open-angle glaucoma (POAG) cases naïve to prior incisional glaucoma surgery. We examined 119 consecutive glaucoma patients retrospectively, who received a TE or XEN for medically uncontrolled POAG. Intraocular pressure (IOP), amount of IOP-lowering medication, mean deviation of standard automated perimetry and peripapillary RNFL thickness were evaluated during the first 24 months after surgery. Fifty eyes were treated with TE and 69 eyes with XEN. Mean IOP decreased from 25.1 ± 0.8 to 13.3 ± 0.6 mm Hg (p < 0.01) and mean number of IOP-lowering eye drops from 3.2 ± 0.2 to 0.4 ± 0.1 (p < 0.01) 24 months after TE. In 69 eyes undergoing XEN, mean IOP dropped from 24.8 ± 0.6 to 15.0 ± 0.4 mm Hg (p < 0.01) and medication from 3.0 ± 0.1 to 0.6 ± 0.1 (p < 0.01) during the 24 months follow-up. Mean deviation of standard automated perimetry remained stable in TE (8.5 ± 0.7 to 8.1 ± 0.8 dB; p = 0.54) and XEN group (11,0 ± 0.5 to 11.5 ± 0.5 dB; p = 0.12) after 24 months, while mean RNFL thickness further deteriorated in the TE (−2.28 ± 0.65 µm/year) and XEN (−0.68 ± 0.34 µm/year) group. Postoperative RNFL loss develops after TE and XEN despite effective and significant lowering of IOP and amount of IOP-lowering medication. RNFL loss was more pronounced in the first year after glaucoma surgery.

Higher chronic stress and less satisfaction with GP communication in migrants with unemployment experience: data from the representative German DEGS1 and the GPCare-1 study.

BACKGROUND: The impact of unemployment on health is well studied. However, information on associations of unemployment, migration background and general practitioner-patient communication is scarce. METHODS: Data from the representative German Health Interview and Examination Survey for Adults (DEGS1) of individuals in working age (n = 5938) were analysed stratified by unemployment and migration background. Using official weighting factors, the prevalence of chronic stress, having ≥1 chronic disease, having a GP and GP visits in the last 12 months was determined. Multivariate regression models were analysed for associations between unemployment, migration background, and other socio-demographic characteristics with GP visits and chronic stress. Data from the General Practice Care-1 (GPCare-1) study (n = 813 patients) were analysed for differences in patient-physician communication between unemployed with and without migration background. Reverse proportional odds models were estimated for associations of unemployment and migration background with physician-patient communication. RESULTS: In the DEGS1, 21.5% had experienced unemployment (n = 1170). Of these, 31.6% had a migration background (n = 248). Compared to unemployed natives, unemployed with migration background had higher chronic stress (mean: 14.32 vs. 13.13, p = 0.02), while the prevalence of chronic disease was lower (21.7% vs. 30.2%, p = 0.03). They were less likely to have a GP (83.6% vs. 90%, p = 0.02), while GP visits were similar (mean: 3.7 vs. 3.3, p = 0.26). Migration background and unemployment experience were not associated with GP visits, while both factors were significantly associated with higher chronic stress (both: p < 0.01). In GPCare-1, 28.8% had ever experienced unemployment (n = 215). Of these, 60 had a migration background (28.6%). The unemployed with migration background reported less frequently that the GP gives them enough space to describe personal strains (46.5% vs. 58.2%; p = 0.03), and that their problems are taken very seriously by their GP (50.8% vs. 73.8%; p = 0.04). In multivariate analyses, migration background showed a lower probability of having enough space to describe personal strains and feeling that problems were taken very seriously. CONCLUSION: Unemployment experience and migration background were associated with higher chronic stress. Only migration background was associated with less satisfaction regarding physician-patient communication.

Higher Work-Privacy Conflict and Lower Job Satisfaction in GP Leaders and Practice Assistants Working Full-Time Compared to Part-Time: Results of the IMPROVEjob Study.

Background: Work-privacy conflict (WPC) has become an important issue for medical professionals. The cluster-randomized controlled IMPROVEjob study aimed at improving job satisfaction (primary outcome), with additional outcomes such as examining the work-privacy conflict in German general practice personnel. Using baseline data of this study, the relationship between work-privacy conflict and job satisfaction (JS) was analyzed. In addition, factors associated with higher WPC were identified. Methods: At baseline, 366 participants (general practitioners (GPs) in leadership positions, employed general practitioners, and practice assistants) from 60 German practices completed a questionnaire addressing socio-demographic data and job characteristics. Standardized scales from the German version of the COPSOQ III requested data concerning job satisfaction and work-privacy conflict. Both scores range from 0 (lowest) to 100 (highest). Multilevel analysis accounted for the clustered data. Statistical analyses were performed using IBM SPSS and RStudio software, with a significance level set at p < 0.05. Results: Job satisfaction was 77.16 (mean value; SD = 14.30) among GPs in leadership positions (n = 84), 79.61 (SD = 12.85) in employed GPs (n = 28), and 72.58 (SD = 14.42) in practice assistants (n = 254). Mean values for the WPC-scale were higher for professionals with more responsibilities: GPs in leadership positions scored highest with 64.03 (SD = 29.96), followed by employed physicians (M = 45.54, SD =30.28), and practice assistants (M = 32.67, SD = 27.41). General practitioners and practice assistants working full-time reported significantly higher work-privacy conflict than those working part-time (p < 0.05). In a multilevel analysis, work-privacy conflict was significantly associated with job satisfaction (p < 0.001). A multiple regression analysis identified working hours, as well as and being a practice owner or an employed physician as factors significantly influencing WPC. Discussion: WPC was high among general practice leaders and practice personnel working full-time. Future interventions to support practice personnel should focus on reducing WPC, as there is good evidence of its effects on job satisfaction.

Proteome and Network Analysis Provides Novel Insights Into Developing and Established Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side-effect of cancer therapies. So far, the development of CIPN cannot be prevented, neither can established CIPN be reverted, often leading to the cessation of necessary chemotherapy. Thus, there is an urgent need to explore the mechanistic basis of CIPN to facilitate its treatment. Here we used an integrated approach of quantitative proteome profiling and network analysis in a clinically relevant rat model of paclitaxel-induced peripheral neuropathy. We analysed lumbar rat DRG at two critical time points: (1) day 7, right after cessation of paclitaxel treatment, but prior to neuropathy development (pre-CIPN); (2) 4 weeks after paclitaxel initiation, when neuropathy has developed (peak-CIPN). In this way we identified a differential protein signature, which shows how changes in the proteome correlate with the development and maintenance of CIPN, respectively. Extensive biological pathway and network analysis reveals that, at pre-CIPN, regulated proteins are prominently implicated in mitochondrial (dys)function, immune signalling, neuronal damage/regeneration, and neuronal transcription. Orthogonal validation in an independent rat cohort confirmed the increase of ß-catenin (CTNNB1) at pre-CIPN. More importantly, detailed analysis of protein networks associated with ß-catenin highlights translationally relevant and potentially druggable targets. Overall, this study demonstrates the enormous value of combining animal behaviour with proteome and network analysis to provide unprecedented insights into the molecular basis of CIPN. In line with emerging approaches of network medicine our results highlight new avenues for developing improved therapeutic options aimed at preventing and treating CIPN.