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Abstract Background Psychiatric emergencies pose a special challenge for emergency physicians. It is known from other areas of medicine that the influence of a doctor’s gender can have an impact on the type of treatment and quality of patient care. However, this has not yet been investigated in the context of prehospital care in psychiatric emergencies. Objectives To identify whether the gender of the prehospital emergency physicians has an influence on the “on-scene” time, treatment strategy and on the potential escalation of interventions for patients with a psychiatric diagnosis. Methods A retrospective cohort analysis of emergency missions with a psychiatric diagnosis was performed between January 1, 2015 and December 31, 2021 at the Department of Emergency Medicine, Department of Anesthesiology and Intensive Care Medicine, University Hospital Ulm, Germany. Results 2882 emergency missions with a psychiatric indication/prehospital psychiatric diagnosis were studied and divided into: intoxication (n = 1343, 46.6%), suicidal behavior (n = 488, 16.9%), exceptional mental situation (n = 282, 9.8%), agitation (n = 262, 9.1%), anxiety and panic disorders (n = 262, 9.1%) and “psychiatric miscellaneous” (n = 245, 8.5%). Inpatient hospitalization occurred in 67.9% (n = 1958) of emergency missions. Of these, 20.3% (n = 392) were admitted directly to a psychiatric hospital. Male emergency physicians had a slightly longer "on-scene" time for psychiatric emergencies than female emergency physicians (p = 0.024). However, the variance in "on-scene" time for all interventions was significantly greater for female emergency physicians than for male emergency physicians (p = 0.025). Male emergency physicians were significantly more likely than their female counterparts to administer intravenous hypnotics in prehospital psychiatric emergencies (p = 0.001). For psychiatric patients who refused medically indicated inpatient psychiatric admission (“involuntary psychiatric admission”), male and female emergency physicians were equally likely to take the required action (p = 0.522). However, male emergency physicians were significantly more likely to administer an intravenous hypnotic to enforce involuntary admission (p = 0.009). Conclusions Similar to other medical specialties where the influence of physician gender on patient care is certainly relevant, the gender of prehospital emergency physicians also appears to influence their prehospital management strategy in psychiatric emergencies. The influence of gender is sometimes subtle and limited to specific aspects, such as the administration of hypnotics. Prospective study designs are needed to thoroughly investigate the influence of the gender of the prehospital emergency physician on the quality of care in psychiatric emergencies. Trial registration The study was approved by the ethics committee of the University Ulm, Trial-Code No. 110/22 and was prospectively registered in the German Clinical Trials Register (DRKS-ID: DRKS00031237). Patient information was not required for retrospective data analysis.

Over decades, pesticide regulations have cycled between approval and implementation, followed by the discovery of negative effects on nontarget organisms that result in new regulations, pesticides, and harmful effects. This relentless pattern undermines the capacity to protect the environment from pesticide hazards and frustrates end users that need pest management tools. Wild pollinating insects are in decline, and managed pollinators such as honey bees are experiencing excessive losses, which threatens sustainable food security and ecosystem function. An increasing number of studies demonstrate the negative effects of field-realistic exposure to pesticides on pollinator health and fitness, which contribute to pollinator declines. Current pesticide approval processes, although they are superior to past practices, clearly continue to fail to protect pollinator health. In the present article, we provide a conceptual framework to reform cyclical pesticide approval processes and better protect pollinators.

Abstract Background Advancing the engineering of photosynthesis-based prokaryotic cell factories is important for sustainable chemical production and requires a deep understanding of the interplay between bioenergetic and metabolic pathways. Rearrangements in photosynthetic electron flow to increase the efficient use of the light energy for carbon fixation must be balanced with a strong carbon sink to avoid photoinhibition. In the cyanobacterium Synechocystis sp. PCC 6803, the flavodiiron protein Flv3 functions as an alternative electron acceptor of photosystem I and represents an interesting engineering target for reorganizing electron flow in attempts to enhance photosynthetic CO2 fixation and increase production yield. Results We have shown that inactivation of Flv3 in engineered sucrose-excreting Synechocystis (S02:Δflv3) induces a transition from photoautotrophic sucrose production to mixotrophic growth sustained by sucrose re-uptake and the formation of intracellular carbon sinks such as glycogen and polyhydroxybutyrate. The growth of S02:Δflv3 exceeds that of the sucrose-producing strain (S02) and demonstrates unforeseen proteomic and metabolomic changes over the course of the nine-day cultivation. In the absence of Flv3, a down-regulation of proteins related to photosynthetic light reactions and CO2 assimilation occurred concomitantly with up-regulation of those related to glycolytic pathways, before any differences in sucrose production between S02 and S02:Δflv3 strains were observed. Over time, increased sucrose degradation in S02:Δflv3 led to the upregulation of respiratory pathway components, such as the plastoquinone reductase complexes NDH-11 and NDH-2 and the terminal respiratory oxidases Cyd and Cox, which transfer electrons to O2. While glycolytic metabolism is significantly up-regulated in S02:Δflv3 to provide energy for the cell, the accumulation of intracellular storage compounds and the increase in respiration serve as indirect sinks for photosynthetic electrons. Conclusions Our results show that the presence of strong carbon sink in the engineered sucrose-producing Synechocystis S02 strain, operating under high light, high CO2 and salt stress, cannot compensate for the lack of Flv3 by directly balancing the light transducing source and carbon fixing sink reactions. Instead, the cells immediately sense the imbalance, leading to extensive reprogramming of cellular bioenergetic, metabolic and ion transport pathways that favor mixotrophic growth rather than enhancing photoautotrophic sucrose production.

Background: There are limited treatment options for patients with advanced or metastatic gastrointestinal stromal tumours (GISTs) that lack mutations targetable by tyrosine kinase inhibitors (TKIs) or that have developed resistance to TKIs. Gastrin-releasing peptide receptor (GRPR) theranostics may offer a viable option in GISTs. However, the expression of the GRPR in GIST has not been extensively studied. Materials and methods: GRPR expression was evaluated using immunohistochemistry in two separate tissue microarrays from patients treated at Sahlgrenska University Hospital, one from the pre-TKI era (1983-2001) and the other from the post-TKI era (2014-2020). In total, 205 tumour samples were characterized as having low/none or moderate/high expression of the GRPR, and these were correlated with clinical characteristics and survival outcomes. Results: In total, 80% of the tumour samples exhibited moderate or high expression of GRPR. GRPR expression was not associated with gender, age, tumour location, or risk group, as defined by the modified National Institutes of Health (NIH) consensus criteria. Neoadjuvant treatment with TKI was correlated with low/none GRPR expression (P = 0.04). In patients who underwent surgery with curative intent and did not receive neoadjuvant treatment, GRPR expression was not associated with survival outcomes. Conclusions: This study is the first to investigate GRPR expression in a large cohort of GIST tumours. Our results demonstrate that most GIST tumours exhibit a moderate to high expression of the receptor, suggesting that GRPR theranostics could be a viable option for TKI-resistant GIST. Interestingly, tumours that were pretreated with TKI showed lower expression levels of GRPR, indicating a need for further studies to explore this finding.

Rafflesia is an endangered endophytic holoparasitic plant that lives the majority of its life inside the tissues of its sole plant host, Tetrastigma. Rafflesia floral buds emerge to produce the world’s largest single flower. Like other plants, holoparasites harbor a diverse microbiome, the role(s) of which has remained largely unstudied. We characterized the bacterial microbiome of seeds of Rafflesia speciosa and cuttings of its host. We found evidence that R. speciosa seed has similar bacterial profiles to its infected host, which suggests that seeds sequester certain host bacteria, as well as acquire unique bacterial taxa from biotic associates of the fruit. We did not find evidence of mycorrhizal taxa in the microbiome. This is the first study of the microbial endophytes associated with any Rafflesia species and its host, a tripartite holobiont, and provides insights on its cryptic microbial partners. We discuss how this may aid horticultural propagation of Rafflesia.

Abstract Background To curb human-made carbon-dioxide emissions, the European Union will introduce carbon pricing for buildings and transport in 2027. Central and East European (CEE) countries are pressured to embark on ambitious decarbonization pathways leading to carbon-neutral economies by 2050. This paper is the first to investigate the public acceptance of and the willingness to pay (WTP) for a carbon tax in a CEE country, Hungary. It analyzes the support-increasing effects of five revenue-recycling mechanisms (tax cuts, green spending, support for poor households, funding for health care and education, and debt reduction), a wider range than covered in previous studies. A national face-to-face survey of 3013 adults on public attitudes to climate change, conducted in summer 2022, is the main method of data collection. This is combined with secondary analysis of related statistics and documentary analysis of relevant materials. Results The results show low public acceptance, with only a modest increase from 20.3% to 27.3% due to revenue recycling. This is accompanied by low WTP values and WTP increases. All these are lower than those found in Western surveys. A novel empirical result is the relative popularity of public health care and education in revenue recycling, though differences in revenue-recycling preferences are apparent between those who accept a carbon tax even without a redistribution mechanism and those who are willing to pay only if redistribution is included. Green spending also performed relatively well, while supporting the poor fared less well, albeit with relatively high WTP values. Reducing taxes and public debt were the least likely to instigate carbon-tax acceptance. Conclusions The results highlight the importance of carefully assessing the distributional impact of implementing carbon pricing mechanisms and thoroughly integrating social considerations into climate policy. Based on this, as well as the analysis of the social conditions and political economy of climate policy development in Hungary, policies—such as a gradually increasing carbon tax, social cushioning, legal earmarking of carbon-tax revenues, and policy bundling—are proposed to make carbon pricing socially tolerable and politically acceptable. The findings and conclusions might also be relevant for other parts of the CEE region.

Abstract Aerosols influence weather and climate by interacting with radiation through absorption and scattering. These effects heavily rely on the optical properties of aerosols, which are mainly governed by attributes such as morphology, size distribution, and chemical composition. These attributes undergo continuous changes due to chemical reactions and aerosol micro-physics, resulting in significant spatio-temporal variations. Most atmospheric models struggle to incorporate this variability because they use pre-calculated tables to handle aerosol optics. This offline approach often leads to substantial errors in estimating the radiative impacts of aerosols along with posing significant computational burdens. To address this challenge, we introduce a computationally efficient and robust machine learning approach called MieAI. It allows for relatively inexpensive calculation of the optical properties of internally mixed aerosols with a log-normal size distribution. Importantly, MieAI fully incorporates the variability in aerosol chemistry and microphysics. Our evaluation of MieAI against traditional Mie calculations, using number concentrations from the ICOsahedral Nonhydrostatic model with Aerosol and Reactive Trace gases (ICON-ART) simulations, demonstrates that MieAI exhibits excellent predictive accuracy for aerosol optical properties. MieAI achieves this with errors well within 10%, and it operates more than 1000 times faster than the benchmark approach of Mie calculations. Due to its generalized nature, the MieAI approach can be implemented in any chemistry transport model which represents aerosol size distribution in the form of log-normally distributed internally mixed modes. This advancement has the potential to replace frequently employed look-up tables and plays a substantial role in the ongoing attempts to reduce uncertainties in estimating aerosol radiative forcing.

# Introduction and Purpose Knee osteoarthritis (OA) is a common condition that limits function and reduces quality of life. Total knee arthroplasty (TKA) is a surgical procedure that replaces the joint surfaces to address anatomical changes due to knee OA. While TKA improves symptoms and function, postoperative impairments are common, including reduced quadriceps strength. Blood flow restriction (BFR) may be a viable option for patients following TKA, as it can improve strength with a minimal amount of joint loading compared to traditional strength training. The purpose of this case report is to describe the impact of BFR use in an individual after TKA, employing pain measurements, quantitative sensory testing, patient-reported outcome measures, physical performance tests, and muscle strength and power testing to explore potential treatment effects and identify potential predictors of response for future studies. # Case Description A 49-year-old former female triathlete with a history of knee injury and arthroscopic surgery underwent a right TKA and sought physical therapy (PT) due to pain, limited range of motion (ROM), and knee instability during weight bearing activity. PT interventions included manual therapy, gait training, and a home program. Despite participating in supervised PT, she had persistent pain, ROM deficits, and muscle weakness 16 weeks following TKA. BFR was incorporated into her home program, 16-weeks postoperatively. The Short Form McGill Pain Questionnaire-2 (SF-MPQ-2) and Numeric Pain Rating Scale (NPRS) were used to measure pain. Quantitative sensory testing included pressure pain threshold (PPT) and two-point discrimination (TPD) to measure change in sensory perception. Patient-reported outcome measures to assess perceived physical function were the Knee injury and Osteoarthritis Outcome Score (KOOS) and the KOOS- Joint Replacement (KOOS-JR). Physical performance was measured through the 30-second fast walk test (30SFW), timed stair climb test (SCT), 30-second chair standing test (CST), and the timed up and go (TUG). Knee ROM was assessed through standard goniometry. Knee extensor and flexor muscle strength and power were measured with an instrumented dynamometer for isokinetic and isometric testing, generating a limb symmetry index (LSI). # Outcomes Pain and quantitative sensory testing achieved clinically meaningful improvement suggesting reduced sensitivity during and after BFR utilization. Perceived physical function and symptoms significantly improved, particularly in sports and recreation activities, and were best captured in the KOOS, not the KOOS-JR. Physical performance reached clinically meaningful improvement in walking speed, chair stand repetitions, and timed stair climb tests after BFR. Isokinetic and isometric strength and power in knee extensors and flexors increased significantly after BFR compared to the uninvolved leg as determined by LSI. # Discussion In this case, BFR appeared to be a safe and well-tolerated intervention. The results suggest potential benefits in terms of increased function, strength, power, and reduced pain in this specific person after TKA. Comprehensive pain and sensory assessments alongside clinical measures may help identify suitable patients for BFR after TKA. The KOOS-Sport & Recreation subscale may be more responsive to monitor functional recovery compared to the KOOS-JR, possibly due to the subject's athletic background. # Level of Evidence 4

Editorial introducing a new special issue in the journal.

This community service aims to increase the knowledge and skills of fishermen in Pengambengan village, Jembrana Regency, Bali in creating innovative portable rollers as an effective and efficient tool for moving boats. The method of implementing this service uses training with data collection techniques in the form of observation, interviews and documentation. Evaluation of the success level of this service uses a questionnaire instrument, which is analyzed descriptively and quantitatively. The results of this service activity show that fishermen can understand well the innovation of portable rollers as an effective and efficient tool for moving boats. Apart from that, fishermen have been able to create and improve existing wheel innovations. The finished rolling innovation can be used by fishermen properly and correctly when moving boats/jukungs to places that are safer from high tides.

Bullying by peers remains a serious problem facing adolescents. A key social support for adolescents is their parents. The unique contributions of specific dimensions comprising authoritative parenting, and adolescents' involvement in bullying situations was investigated. Self-report data were collected from 125 grade 7 students and 100 grade 8 students (60% female; mean age = 12.74 years). Model testing indicated a positive relationship between parent support, beliefs against aggression, high levels of communication, and low levels of bullying and victimization, both in self-reports, and in effectiveness of problem-solving in hypothetical bullying situations. Results indicate that warm, supportive parenting influences the way adolescents consult with their parents about how to manage conflict, deal with bullying issues, and identify solutions to interpersonal problems. The implications of these findings may influence the comprehensiveness of prevention and intervention models that focus on the aspects of parental education.

Introduction Empowering people living with multimorbidity (multiple chronic conditions) to gain greater confidence in managing their health can enhance their quality of life. Education focused on self-management is a key tool for fostering patient empowerment and is mostly provided on an individual basis. Virtual communities of practice (VCoP) present a unique opportunity for online education in chronic condition self-management within a social context. This research aims to evaluate the effectiveness/cost-effectiveness of individualised, online self-management education compared with VCoP among middle-aged individuals living with multiple chronic conditions.Methods and analysis People aged 30–60, living with ≥2 chronic conditions and receiving care in primary care (PC) centres and outpatient hospital-based clinics in Madrid and Canary Islands will enrol in an 18-month parallel-design, blinded (intervention assessment and data analysts), pragmatic (adhering to the intention-to-treat principle), individually randomised trial. The trial will compare two 12-month web-based educational offers of identical content; one delivered individually (control) and the other with online social interaction (VCoP, intervention). Using repeated measures mixed linear models, with the patient as random effect and allocation groups and time per group as fixed effects, we will estimate between-arm differences in the change in Patient Activation Measure from baseline to 12 months (primary endpoint), including measurements at 6-month and 18-month follow-up. Other outcomes will include measures of depression and anxiety, treatment burden, quality of life. In addition to a process evaluation of the VCoP, we will conduct an economic evaluation estimating the relative cost-effectiveness of the VCoP from the perspectives of both the National Health System and the Community.Ethics and dissemination The trial was approved by Clinical Research Ethics Committees of Gregorio Marañón University Hospital in Madrid/Nuestra Señora Candelaria University Hospital in Santa Cruz de Tenerife. The results will be disseminated through workshops, policy briefs, peer-reviewed publications and local/international conferences.Trial registration number NCT06046326.

Abstract Cognitive impairment (CI) is very common in patients with Parkinson’s Disease (PD) and progressively develops on a spectrum from mild cognitive impairment (PD-MCI) to full dementia (PDD). Identification of PD patients at risk of developing cognitive decline, therefore, is unmet need in the clinic to manage the disease. Previous studies reported that oral microbiota of PD patients was altered even at early stages and poor oral hygiene is associated with dementia. However, data from single modalities are often unable to explain complex chronic diseases in the brain and cannot reliably predict the risk of disease progression. Here, we performed integrative metaproteogenomic characterization of salivary microbiota and tested the hypothesis that biological molecules of saliva and saliva microbiota dynamically shift in association with the progression of cognitive decline and harbor discriminatory key signatures across the spectrum of CI in PD. We recruited a cohort of 115 participants in a multi-center study and employed multi-omics factor analysis (MOFA) to integrate amplicon sequencing and metaproteomic analysis to identify signature taxa and proteins in saliva. Our baseline analyses revealed contrasting interplay between the genus Neisseria and Lactobacillus and Ligilactobacillus genera across the spectrum of CI. The group specific signature profiles enabled us to identify bacterial genera and protein groups associated with CI stages in PD. Our study describes compositional dynamics of saliva across the spectrum of CI in PD and paves the way for developing non-invasive biomarker strategies to predict the risk of CI progression in PD.

Abstract Background Understanding how to implement innovations in primary care practices is key to improve primary health care. Aiming to contribute to this understanding, we investigate the implementation of a clinical decision support system (CDSS) as part of the innovation fund project AdAM (01NVF16006). Originating from complexity theory, the practice change and development model (PCD) proposes several interdependent factors that enable organizational-level change and thus accounts for the complex settings of primary care practices. Leveraging the PCD, we seek to answer the following research questions: Which combinations of internal and external factors based on the PCD contribute to successful implementation in primary care practices? Given these results, how can implementation in the primary care setting be improved? Methods We analyzed the joint contributions of internal and external factors on implementation success using qualitative comparative analysis (QCA). QCA is a set-theoretic approach that allows to identify configurations of multiple factors that lead to one outcome (here: successful implementation of a CDSS in primary care practices). Using survey data, we conducted our analysis based on a sample of 224 primary care practices. Results We identified two configurations of internal and external factors that likewise enable successful implementation. The first configuration enables implementation based on a combination of Strong Inside Motivation, High Capability for Development, and Strong Outside Motivation; the second configuration based on a combination of Strong Inside Motivators, Many Options for Development and the absence of High Capability for Development. Conclusion In line with the PCD, our results demonstrate the importance of the combination of internal and external factors for implementation outcomes. Moreover, the two identified configurations show that different ways exist to achieve successful implementation in primary care practices. Trial registration AdAM was registered on ClinicalTrials.gov ( NCT03430336 ) on February 6, 2018.

This study analyzes the dynamics of short-term treatment response to the first intravitreal faricimab injection in eyes with diabetic macular edema (DME). This retrospective, single-center, clinical trial was conducted at the Department of Ophthalmology, University Hospital Zurich. Patients with treatment-naïve and pretreated DME were included. Patient chart data and imaging were analyzed. Safety and efficacy (corrected visual acuity (CVA), central subfield thickness (CST), and signs of intraocular inflammation (IOI)) of the first faricimab intravitreal therapy (IVT) were evaluated weekly until 4 weeks after injection. Forty-three eyes (81% pretreated) of 31 patients were included. Four weeks after the first faricimab IVT, CVA remained stable and median CST (µm) decreased significantly (p < 0.001) from 325.0 (293.5–399.0) at baseline to 304.0 (286.5–358.0). CVA at week 4 was only associated with baseline CVA (p < 0.001). CST was the only predictive variable (p = 0.002) between baseline and week 4 CST. Weekly safety assessments did not show any sign of clinically significant IOI. This study suggests faricimab is an effective treatment for (pretreated) DME, showing structural benefit 1 month following the first injection without short-term safety signals.

Background and Objectives: Scuba divers often experience persistent inert gas narcosis (IGN) even after surfacing. This study aimed to test the hypothesis that breathing oxygen (O2) before surfacing can reduce postdive IGN. Materials and Methods: A group of 58 experienced divers underwent a 5 min dive at a depth of 50 m in a multi-place hyperbaric chamber. They were decompressed using air (air group). Another group of 28 divers (O2 group) breathed 100% O2 during the end of decompression. Prior to and after the dive, all participants performed the Sharpened Romberg test (SRT) and a modified tweezers test. Results: In the air group, the number of positive SRT results increased postdive (47% vs. 67%), indicating a greater impairment in the vestibular system (Cohen’s d = 0.41). In the O2 group, the percentage of positive SRT results remained constant at 68% both before and after the dive. In terms of the modified tweezers test, the air group showed no significant change in the number of picked beads (40 ± 9 vs. 39 ± 7), while the O2 group demonstrated an increase (36 ± 7 vs. 44 ± 10) (Cohen’s d = 0.34). Conclusion: The results reveal that the SRT revealed a negative effect of nitrogen (N2) on the vestibular system in the air group. The increased number of beads picked in the O2 group can be attributed to the learning effect, which was hindered in the air group. Consistent with our hypothesis, breathing O2 during decompression appears to reduce postdive IGN.

Abstract Background Prehospital care of psychiatric patients often relies on the medical experience of prehospital emergency physicians (PHEPs). The psychiatrists (PSs) involved in the further treatment of psychiatric patients also often rely on their experience. Furthermore, the interaction between PHEPs and PSs is characterized by interaction problems and different approaches in the prehospital care of the psychiatric emergency. Objectives To analyze the phenomenon of “medical experience” as a cause of possible interaction-related problems and assess its impact on the prehospital decision-making process between prehospital emergency physicians and psychiatrists. Methods The retrospective data analysis was conducted between November 2022 and March 2023. Medical experience was defined as follows, based on the demographic information collected in the questionnaires: For PHEPs, the period since obtaining the additional qualification in emergency medicine was defined as a surrogate marker of medical experience: (i) inexperienced: < 1 year, (ii) experienced: 1–5 years, (iii) very experienced: > 5 years. For PSs, age in years was used as a surrogate parameter of medical experience: (i) inexperienced: 25–35 years, (ii) experienced: 35–45 years, (iii) very experienced: > 45 years. Results Inexperienced PSs most frequently expressed anxiety about the psychiatric emergency referred by a PHEP (27.9%). Experienced PHEPs most frequently reported a lack of qualifications in handling the care of psychiatric emergencies (p = 0.002). Very experienced PHEPs were significantly more likely to have a referral refused by the acute psychiatric hospital if an inexperienced PS was on duty (p = 0.01). Experienced PHEPs apply an intravenous hypnotic significantly more often (almost 15%) than PSs of all experience levels (p = 0.001). In addition, very experienced PHEPs sought prehospital phone contact with acute psychiatry significantly more often (p = 0.01). Conclusion PHEPs should be aware that the PS on duty may be inexperienced and that treating emergency patients may cause him/her anxiety. On the other hand, PHEPs should be receptive to feedback from PS who have identified a qualification deficiency in them. Jointly developed, individualized emergency plans could lead to better prehospital care for psychiatric emergency patients. Further training in the prehospital management of psychiatric disorders is needed to minimize the existing skills gap among PHEPs in the management of psychiatric disorders.

Abstract Background In 2014 a new system for drug expenditures, the Wirkstoffvereinbarung (WSV, English: Active substance agreement) was implemented in Bavaria. In pre-defined indication groups, economic prescription of medications shall be enabled based on the selection, quantity, and proportion of an individual drug. Ambulatory care physicians receive quarterly trend reports on their prescribing behavior. This study examines physicians’ perceptions of the WSV. Methods Qualitative interviews (n = 20) and seven focus groups (n = 36) were conducted with ambulatory care physicians (e.g. general practitioners, cardiologists, pulmonologists). The methodology followed Qualitative Content Analysis. Results Physicians generally accepted the necessity of prescribing economically. The majority of them rated the WSV positively and better than the previous system. As an improvement, they especially named timely feedback in form of easily understandable trend reports, encouraging self-reflection as well as allowing early control options. Problems perceived were drug discount contracts that were strongly criticized as leading to patients mixing up medications. Some perceived constraints of therapeutic freedom. Conclusions The implementation of the WSV is mostly viewed positively by physicians. The restrictions of therapeutic freedom partially perceived might be met by improved information on the reasons why some drugs are rated as less economical than others. Trial registration number Main ID: DRKS00019820 (German Register of Clinical Studies and World Health Organization).

Social media influencers have become an indispensable part of social media, informing audiences, especially young ones, about various topics, such as beauty, lifestyle, or food. Recently more political influencers have emerged, and regular influencers have increasingly taken positions on political and societally relevant topics, including climate justice and gender equality. Yet, empirical evidence on how both types of influencers are perceived by their audiences and how they might impact young audiences regarding political action is scarce. Hence, the present study set out to investigate adolescents’ and young adults’ use and perception of social media influencers in the context of political information dissemination, opinion formation, and mobilization. With the help of qualitative interviews of young people in Germany (16–22 years), we show that while the mainstream media seems to still be the primary source of political information, influencers focused on politics are increasingly used to make sense of this information. The presumed impact ranges from amplifying the effects of existing opinions to opinion formation and changes in voting intentions based on the assessment provided by the influencer. Regular influencers who talk about political topics occasionally are not perceived as reliable sources of political information.

Abstract Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors. PGLs can further be divided into sympathetic (sPGLs) and head-and-neck (HN-PGLs). There are virtually no treatment options, and no cure, for metastatic PCCs and PGLs (PPGLs). Here, we composed a tissue microarray (TMA) consisting of 149 PPGLs, reflecting clinical features, presenting as a useful resource. Mutations in the pseudohypoxic marker HIF-2α correlate to an aggressive tumor phenotype. We show that HIF-2α localized to the cytoplasm in PPGLs. This subcompartmentalized protein expression differed between tumor subtypes, and strongly correlated to proliferation. Half of all sPGLs were metastatic at time of diagnosis. Cytoplasmic HIF-2α was strongly expressed in metastatic sPGLs and predicted poor outcome in this subgroup. We propose that higher cytoplasmic HIF-2α expression could serve as a useful clinical marker to differentiate paragangliomas from pheochromocytomas, and may help predict outcome in sPGL patients.

Background: The proximal humerus is the second-most common anatomic site for osteonecrosis, a condition of disrupted blood supply leading to death of bone tissue, with resultant shoulder pain and dysfunction. Core decompression is a viable joint-preserving surgical intervention that aims to improve local blood supply and restore bone health prior to bony collapse. Indications: Humeral head osteonecrosis has numerous underlying causes, most commonly the sequelae of prior trauma, chronic use of systemic corticosteroids, sickle cell disease, and alcohol abuse. Core decompression may be indicated in the early, pre-collapse stages of osteonecrosis, whereas more advanced stages of disease are commonly indicated for joint reconstruction procedures, such as bone grafting or arthroplasty. Technique Description: With the patient in the beach chair position, bone marrow aspirate concentrate (BMAC) is harvested through a percutaneous incision along the anterolateral proximal humerus. While viewing through a standard posterior portal, a transtibial anterior cruciate ligament (ACL) guide is placed through an anterior portal at a site on the humeral head surface, centered at the area of greatest humeral head bone edema as identified on preoperative magnetic resonance imaging. A guide pin is placed through a lateral portal within the ACL guide, to the subchondral bone. A 7.0-mm reamer is applied over the guidewire, followed by administration of demineralized bone matrix soaked in BMAC into the reamed channel within the proximal humerus. Results: In patients with early stages of humeral head osteonecrosis, core decompression confers superior clinical outcomes with reduced rates of subsequent surgical procedures compared with nonoperative treatment. Core decompression has shown to reduce the radiographic progression of osteonecrosis. Further research is necessary to determine the additional clinical benefits of augmentation with orthobiologic agents, such as BMAC. Conclusion: Arthroscopic-assisted core decompression is a valuable, minimally invasive surgical treatment for early-stage proximal humerus osteonecrosis. Adjunctive treatment with BMAC and demineralized bone matrix may enhance clinical outcomes. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

BackgroundThe transition of patients between inpatient and outpatient care can lead to adverse events and medication-related problems due to medication and communication errors, such as medication discontinuation, the frequency of (re-)hospitalizations, and increased morbidity and mortality. Older patients with multimorbidity and polypharmacy are particularly at high risk during transitions of care. Previous research highlighted the need for interventions to improve transitions of care in order to support information continuity, coordination, and communication. The HYPERION-TransCare project aims to improve the continuity of medication management for older patients during transitions of care.Methods and findingsUsing a qualitative design, 32 expert interviews were conducted to explore the perspectives of key stakeholders, which included healthcare professionals, patients and one informal caregiver, on transitions of care. Interviews were conducted between October 2020 and January 2021, transcribed verbatim and analyzed using content analysis. We narratively summarized four main topics (stakeholders' tasks, challenges, ideas for solutions and best practice examples, and patient-related factors) and mapped them in a patient journey map. Lacking or incomplete information on patients' medication and health conditions, inappropriate communication and collaboration between healthcare providers within and across settings, and insufficient digital support limit the continuity of medication management.ConclusionsThe study confirms that medication management during transitions of care is a complex process that can be compromised by a variety of factors. Legal requirements and standardized processes are urgently needed to ensure adequate exchange of information and organization of medication management before, during and after hospital admissions. Despite the numerous barriers identified, the findings indicate that involved healthcare professionals from both the inpatient and outpatient care settings have a common understanding.

This article concerns a learning environment in a preschool which includes a preschool teacher and two bilingual children. The article details how an activity of counting is introduced in the course of packing up a game and increasingly turns into an activity of calculation. Thereby the activity engages the participants to demonstrate their competences in terms of language and mathematics rather than (merely) manipulating, arranging and counting objects. The analysis thus exemplifies how, by the use of language as a resource, an interaction in a preschool occasions an activity that may be seen as aiming at a transition between preschool and primary school. Simultaneously, however, it becomes clear that, possibly because this is an unplanned activity, the outcome of this activity may be unequally beneficial for the participants.