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The current article presents and explains methods for clinical examination of the vestibular system that have been used from the 1950s to the present day. It spans 230 years of clinical vestibular research, giving the reader a better overview and filling in the gaps in the history. Whilst only limited topographic regions could be examined in the early years, it is nowadays possible to collect objective results independently of patient compliance. Not only qualitative but also quantitative testing of the three semicircular canals and the otolith organs is now possible in clinical practice., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: Gemäß den Richtlinien des Springer Medizin Verlags werden Autoren und Wissenschaftliche Leitung im Rahmen der Manuskripterstellung und Manuskriptfreigabe aufgefordert, eine vollständige Erklärung zu ihren finanziellen und nichtfinanziellen Interessen abzugeben. Autoren: P.K. Wilcke: A. Finanzielle Interessen: P.K. Wilcke gibt an, dass kein finanzieller Interessenkonflikt besteht. – B. Nichtfinanzielle Interessen: Studentin Christian-Albrecht-Universität zu Kiel (CAU), Promotionsstudentin Universität Hamburg. A.S. Hoffmann: A. Finanzielle Interessen: Nicht im Rahmen dieser Arbeit. – Nicht im Rahmen dieser Arbeit. – B. Nichtfinanzielle Interessen: Oberärztin in der HNO-Klinik am Universitätsklinikum Hamburg-Eppendorf | Stellvertretende Vorsitzende der AG Rhinologie; Mitglied des Vorstands der AG pädiatrische HNO. M. Praetorius: A. Finanzielle Interessen: Nicht im Rahmen dieser Arbeit. – Nicht im Rahmen dieser Arbeit. – B. Nichtfinanzielle Interessen: Stellvertretender Klinikdirektor in der HNO-Klinik am Universitätsklinikum Hamburg-Eppendorf. Wissenschaftliche Leitung: Die vollständige Erklärung zum Interessenkonflikt der Wissenschaftlichen Leitung finden Sie am Kurs der zertifizierten Fortbildung auf www.springermedizin.de/cme . Der Verlag: erklärt, dass für die Publikation dieser CME-Fortbildung keine Sponsorengelder an den Verlag fließen. Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: Triangular fibrocartilage complex (TFCC) tear is often considered to be the cause of ulnar wrist pain. The primary treatment typically involves non-operative methods; however, in cases of persistent symptoms, operative intervention has been proposed as a viable option. Depending on the tear's morphology, treatment may involve debridement (central or radial tear) or repair (peripheral tear). Efficacy of operative treatment has not been studied in a randomised controlled trial., Methods and Analysis: This is a prospective, randomised, controlled, blinded multicentre trial, with two randomisation stratums. The first stratum includes central or radial TFCC tears, while the second stratum comprises peripheral TFCC tears. Each stratum consists of two parallel 1:1 arms, comparing the efficacy of (1) debridement of central or radial tear with placebo surgery and (2) repair of peripheral tear with physiotherapy. Participants are recruited from secondary and tertiary referral hospitals in Denmark, Finland and Sweden.Primary outcome is the Patient-Rated Wrist Evaluation (PRWE) at 1 year. Secondary outcomes include subjective and objective outcome measures at 6 months, 1, 2, 5 and 10 years follow-ups., Ethics and Dissemination: The trial was approved by the Pirkanmaa Hospital District Institutional Review Board in March 2020. All participants will be asked to give a written informed consent. The results of the trial will be disseminated as published articles in peer-reviewed journals., Trial Registration Number: NCT04576169., Competing Interests: Competing interests: AK: Consultant fee paid for by KLS Martin, Two Hand and Wrist courses paid for by KLS Martin, and one Hand course paid for by Osteo-Tech. MPR: Shoulder arthroscopy course, and hand and wrist course paid for by Arthrex; and nerve repair course paid for by Axone. TK: no conflict of interest JJ: no conflict of interest. RG: no conflict of interest. MW: No conflict of interest. AR: No conflict of interest. TA: no conflict of interest. AP: no conflict of interest. CL: no conflict of interest. TT: no conflict of interest. VMM: no conflict of interest. Principal investigators do not have any financial or other competing interest for the overall trial and each study site., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Osteoarthritis in the thumb base (trapeziometacarpal joint, CMC-1 joint) is prevalent, particularly among middle-aged and elderly women, causing significant disability. Conservative treatments, including steroid injections, have been questioned for their efficacy, prompting exploration into alternative therapies such as platelet-rich plasma (PRP) injections. This randomized, double-blinded, controlled trial aims to evaluate the effectiveness of high-concentration PRP (platelet-rich plasma) injection compared to saline (placebo) in reducing pain and disability in patients with thumb base osteoarthritis., Methods: Patients meeting inclusion criteria will be randomized and blinded, with injections administered under sterile conditions and radiological guidance. With a planned sample size of 90 patients recruited from the Department of Hand Surgery at Södersjukhuset, Stockholm, the study will assess pain relief and functional improvement at 3, 6, and 12 months post-injection. The primary outcome measure is pain on load (numerical rating scale) at 6 months, with secondary outcomes including patient-reported outcomes, key pinch, grip strength, abduction of the thumb, and time to intervention within 1 year. Statistical analyses will employ non-parametric tests, chi-square tests, and generalized estimating equations to compare outcomes between the PRP and placebo groups., Discussion: The study aims to provide evidence regarding the efficacy of high-concentration PRP injections for thumb base osteoarthritis. If PRP proves superior to saline in reducing pain and improving function, it could offer a promising alternative treatment. Conversely, if PRP does not demonstrate significant benefits over placebo, its use for this condition is not justified. This study seeks to address the current gap in evidence regarding the efficacy of PRP injections for thumb base osteoarthritis., Trial Registration: The study has been approved by the Swedish Ethical Review Authority (2023-06860-01 and 2024-01238-02) and is registered on ClinicalTrials.gov (NCT06193499) 2024-01-04., Competing Interests: Declarations. Ethics approval and consent to participate: The study has been approved by the Swedish Ethical Review Authority (2023–06860-01 and 2024–01238-02), and the study is registered at ClinicalTrials.gov NCT06193499. Changes in the study protocol will be reported to the Swedish Ethical Review Authority and to ClinicalTrials.gov. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: The objective of this study is to examine the comparative effectiveness of vancomycin and metronidazole in a confirmatory analysis of event-free survival (EFS) after initial infection in patients with Clostridioides difficile from a German multicentre cohort study., Methods: The IBIS multicentre cohort enrolled patients with an index episode of C. difficile infection between August 2017 and September 2020. The primary endpoint was EFS, defined as response to treatment with metronidazole or vancomycin within 10 days of initiation, absence of recurrence and death from any cause up to 90 days post-treatment. A Cox proportional hazards model with inverse probability of treatment weighting was used to investigate the comparative effectiveness of this outcome. Additionally, subgroup analyses were performed based on severe and non-severe infections., Results: Of the 489 patients included, 118 (24%) received initial treatment with metronidazole and 371 (76%) with vancomycin. Of these, 78/118 (66.1%) and 247/371 (66.6%), respectively, responded to treatment within 10 days, neither developed a recurrence nor died within 90 days and thus achieved the outcome of EFS. In the subgroup of non-severe infections, 74/293 patients (25.3%) received metronidazole, and 219/293 (74.7%) received vancomycin. Of these, 33/74 (44.6%) metronidazole patients and 150/219 (68.5%) vancomycin patients survived event free. The Cox proportional hazards model revealed differences in EFS for the overall population and both subgroups (reference metronidazole: all severity levels: hazard ratio [HR] 0.46, [95% CI, 0.33-0.65]; non-severe: HR 0.39; [95% CI, 0.24-0.60]; severe: HR 0.52; [95% CI, 0.28-0.95])., Discussion: Our analysis confirms current changes in guidelines, as it supports the superiority of vancomycin compared with metronidazole across all severity levels., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Patients in out-of-hospital intensive care are usually provided with a tracheal cannula and often additionally receive mechanical ventilation. Less frequently, they receive non-invasive ventilation. Their potential to be weaned from the ventilator and to have their tracheostomy tubes removed must be evaluated twice per year from January 1, 2025 on. If there is a potential for weaning from mechanical ventilation or removal of the tracheostomy tube, referral to a specialized facility is required., Objective: The study aimed at characterizing the specialized institutions which can evaluate the potential of patients to be weaned from the ventilator and to have their tracheostomy tubes removed, and which can perform these tasks as well., Methods: Under the auspices of the German Interdisciplinary Society for Out-of-Hospital Ventilation (DIGAB) and with support from the Working group early neurological-neurosurgical rehabilitation (ENNR) a crosssectional online survey took place., Results: Of 18 participating institutions, 11 (61.1%) were certified by professional societies representing neurorehabilitation, respiratory medicine, anaesthesiology and intensive care or paraplegiology. Most leading physicians were specialists in neurology, followed by pulmonology, anaesthesiology and paediatrics. Many professions with a variety of qualifications worked in these institutions. According to n=10 (55.6%) of the participating instituions, regional treatment capacities for patients from out-of-hospital intensive care, who need hospital admission for weaning from mechanical ventilation or a tracheal cannula, were not sufficient. About one third of the institutions offered televisits., Discussion: Patients in out-of-hospital intensive care need interdisciplinary care, interconnecting out- and inpatient care structures due to medical complexity and participation restrictions. While interdisciplinary teams and a wide spectrum of diagnostic and therapeutic methods were provided in the participating institutions, their structure differed considerably., Conclusion: Quality criteria should be established for centres evaluating the patients' potential to be weaned from the ventilator and to have their tracheostomy tubes removed and performing weaning from mechanical ventilation and tracheal cannulas. Further research is needed to specify those criteria, to quantify inpatient treatment capacities for patients from out-of-hospital intensive care to be weaned from mechanical ventilation or tracheal cannulas,to evaluate the feasibility of weaning from mechanical ventilation and tracheal cannulas in an out-of-hospital setting and to understand the role of telemedicine in the treatment of patients in out-of-hospital intensive care., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The geochemical composition of sediment cores can serve as a proxy for reconstructing past human and nature-driven environmental and climatic changes. We investigated the temporal variation in the concentrations and fluxes of polycyclic aromatic compounds (PACs) which include polycyclic aromatic hydrocarbons (PAHs), oxygenated PAHs, and azaarenes in the Sihailongwan Maar Lake and found that they remained low before 1950. The PAC concentrations and fluxes increased substantially since 1950, which was in good agreement with the fast socio-economic development, industrialization, and associated growth in fossil fuel consumption in China, particularly since the 1980s. After 2010, the PAC fluxes decreased, which was consistent with the implementation of air pollution control policies in China at that time. The concentration ratios of the sums of low to high molecular weight PAHs (LMW-PAHs/HMW-PAHs), benzo[ e ]pyrene/benzo[ a ]pyrene, and benzo[ a ]anthracene-7,12-dione/benzo[ a ]anthracene all decreased from bottom to top of the sediment core, reflecting the rapidly increasing contribution of emissions derived from high-temperature fossil fuel combustion (energy, transport and industry) to the PAC emissions in recent times at the expense of biomass burning. In addition, these data reflect the increasing local sources of PACs in more recent times because of the enhanced human activities in the area surrounding the Maar lake. Our results demonstrate that PAC fluxes and concentrations in sediment cores reflect the regional and national economic development and the efficiency of pollution control measures.

Background: Osteoarthritis (OA) contributes increasingly to disability worldwide. There is ample high-quality research on the treatment of knee and hip OA, whereas research on surgical and non-surgical treatment in hand OA is sparse. Limited evidence suggests that education and exercise may improve pain, function, stiffness, and grip strength in hand OA. The established surgical options in hand OA have disadvantages. Prostheses preserve motion but have a high complication rate, whereas fusions decrease function due to limited movement. There is an unmet need for high-quality research on treatment options for hand OA and a need for the development of effective and safe movement-sparing therapies. This study aims to compare the effects of a motion-preserving surgical treatment (denervation of the proximal interphalangeal (PIP) joint) with a patient education and exercise program on patient-reported outcomes and objective function in painful PIP OA., Methods: In this parallel-group, two-armed, randomized, controlled superiority trial (RCT), 90 participants are assigned to surgical PIP joint denervation or education and exercise. Pain on load 1 year after intervention is the primary outcome measure. Secondary outcome measures include pain at rest, Patient-Rated Wrist and Hand Evaluation (PRWHE), HQ8 score, EQ5D-5L, objective physical function, complications, two-point discrimination, Mini Sollerman, consumption of analgesics, and the need for further surgery. Assessments are performed at baseline, 3 and 6 months, and 1 year after intervention., Discussion: There are no previous RCTs comparing surgical and non-surgical treatment in PIP OA. If patient education plus exercise or PIP denervation improve function, these treatments could be implemented as first-line treatment options in PIP OA. However, if denervation does not achieve better results than non-surgical treatment, it is not justified to use in PIP OA., Trial Registration: Prospectively registered in ClinicalTrials.gov (NCT05980793) on 8 August 2023. URL https://classic., Clinicaltrials: gov/ct2/show/NCT05980793 ., (© 2024. The Author(s).)

Background: The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes., Methods: Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365., Results: The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27-0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6-1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3-4.5) in the control group, p = 0.037., Conclusions: Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial., Trial Registration: ClinicalTrials.gov, NCT03262142, registration date 2017-08-25., (© 2024. The Author(s).)

This pragmatic randomized controlled trial compared lunocapitate fusion (LCF) and four-corner fusion (4CF) for scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) in 64 patients. The primary outcome was change in grip strength from preoperative to 1 year postoperatively. The secondary outcomes were Disability of the Hand, Arm, and Shoulder score, Patient Rated Wrist Evaluation score, EuroQol-5D-3L, range of motion, key pinch strength and complications 12 months postoperatively. Grip strength improved only to a small extent and there was no difference between the groups. No differences were found in the secondary outcomes. In conclusion, LCF is not inferior to 4CF regarding strength, range of motion or patient-reported outcome measures. Level of evidence : I., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Understanding encoded language, such as written words, requires multiple cognitive processes that act in a parallel and interactive fashion. These processes and their interactions, however, are not fully understood. Various conceptual and methodical approaches including computational modeling and neuroimaging have been applied to better understand the neural underpinnings of these complex processes in the human brain. In this study, we tested different predictions of cortical interactions that derived from computational models for reading using dynamic causal modeling. Morse code was used as a model for non-lexical decoding followed by a lexical-decision during a functional magnetic resonance examination. Our results suggest that individual letters are first converted into phonemes within the left supramarginal gyrus, followed by a phoneme assembly to reconstruct word phonology, involving the left inferior frontal cortex. To allow the identification and comprehension of known words, the inferior frontal cortex then interacts with the semantic system via the left angular gyrus. As such, the left angular gyrus is likely to host phonological and semantic representations and serves as a bidirectional interface between the networks involved in language perception and word comprehension., (© 2023. The Author(s).)

This study describes the age and sex distribution, trauma mechanism, treatment and influence of patient-reported outcomes of 6542 carpal fractures from the Swedish Fracture Registry (SFR). The most commonly fractured carpal bone was the scaphoid (60%), followed by the triquetrum (25%), hamate (5%) and trapezium (4%). The mean age at injury was 41 years, and 69% of patients were male. The age and sex distribution of carpal fractures differed substantially between the different carpal bones. Men were more likely to sustain a carpal fracture after high-energy trauma and were more likely to be treated surgically. Carpal fractures had a small negative effect on the Short Musculoskeletal Function Assessment Hand/Arm Index and EQ-5D scores 1 year after the injury. Level of evidence: IV., Competing Interests: Declaration of conflicting interestsThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This review highlights key aspects of treating chronic obstructive pulmonary disease (COPD) exacerbation, focusing on the optimisation of systemic corticosteroid and antibiotic use through personalised treatment using biomarkers. Eosinophil-guided therapy reduces corticosteroid usage which might reduce side effects, while procalcitonin-guided therapy contributes to reduced antibiotic consumption. These approaches, documented through well-conducted randomized controlled trials, suggest the possibility of enhancing COPD exacerbation management, reducing potential side effects, and addressing concerns related to antibiotic resistance., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Although manganese (Mn) is a trace metal essential for humans, chronic exposure to Mn can cause accumulation of this metal ion in the brain leading to an increased risk of neurological and neurobehavioral health effects. This is a concern for welders exposed to Mn through welding fumes. While brain Mn accumulation in occupational settings has mostly been reported in the basal ganglia, several imaging studies also revealed elevated Mn in other brain areas. Since Mn functions as a magnetic resonance imaging (MRI) T1 contrast agent, we developed a whole-brain MRI approach to map in vivo Mn deposition differences in the brains of non-exposed factory controls and exposed welders. This is a cross-sectional analysis of 23 non-exposed factory controls and 36 exposed full-time welders from the same truck manufacturer. We collected high-resolution 3D MRIs of brain anatomy and R1 relaxation maps to identify regional differences using voxel-based quantification (VBQ) and statistical parametric mapping. Furthermore, we investigated the associations between excess Mn deposition and neuropsychological and motor test performance. Our results indicate that: (1) Using whole-brain MRI relaxometry methods we can generate excess Mn deposition maps in vivo, (2) excess Mn accumulation due to occupational exposure occurs beyond the basal ganglia in cortical areas associated with motor and cognitive functions, (3) Mn likely diffuses along white matter tracts in the brain, and (4) Mn deposition in specific brain regions is associated with exposure (cerebellum and frontal cortex) and motor metrics (cerebellum and hippocampus)., Competing Interests: Declaration of competing interest UD reports recent consulting with American Regent, Inc. The other authors do not have any financial conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Certification of centers for weaning from a ventilator in neurological neurosurgical early rehabilitation (NNER) by the German Society for Neurorehabilitation (DGNR) is possible since 1 October 2021., Objective: The results of certification of facilities in the first year after starting the procedure are presented., Material and Methods: As part of the certification process 28 criteria are assessed including a set of mandatory characteristics of the facility. The criteria are divided into structural criteria (i = 7), diagnostic criteria (i = 6), personnel criteria (i = 3), internal organization criteria (i = 7), and quality management criteria (i = 5)., Results: A total of 13 centers were certified in the first year, with a combined total of 283 beds for weaning from a ventilator in the NNER and served 2278 persons to be weaned from a ventilator in the year before certification, with a median of 134 per facility (range 44-414). Only rarely was weaning unsuccessful, requiring conversion to home mechanical ventilation before discharge (invasive home mechanical ventilation median per facility 10 persons, range 2-25; non-invasive home mechanical ventilation median 0 persons, range 0-57). A high level of process and structural quality was documented for the certified centers: across all areas of assessment, the individual certification criteria were met in the vast majority of cases (median degree of complete fulfilment 86%) or met with improvement potentials documented by the auditors (median 11%)., Conclusion: Successful weaning in NNER and a high level of process and structural quality can be demonstrated by the certification results of centers that follow this integrative approach to weaning from a ventilator in a NNER setting., (© 2023. The Author(s).)

Extrapulmonary tuberculosis (TB) in the gastrointestinal tract is a rare, but yet an essential differential diagnosis to patients with complex fistula disease, since the initiation of immunosuppressive therapy for presumed Crohn's disease can lead to a fulminant course of TB. This case report presents a young Danish woman with a progressive complex fistula disease, where cause and treatment were uncovered by interprofessional collaboration between pulmonologists, gastroenterologists and surgeons including a screening test for TB as well as multiple biopsies from the anal fistula tissue., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Background: Local ablation is an important treatment for liver cancer in cases of cirrhosis. Liver failure may occur after ablation, especially in advanced liver diseases. Currently, there is no standardization for peri-interventional risk assessment. The liver maximum capacity test (LiMAx) is used to assess functional liver capacity, but there is a lack of exploration of its use in this context., Objective: The aim of this study was to retrospectively evaluate the usefulness of peri-interventional LiMAx measurements in patients with primary or secondary liver cancer who underwent ablation treatment., Methods: A LiMAx test was performed at 24 hours pre- and postablation in 49 patients. Blood parameters were collected to determine liver function using MELD and ALBI scores. The results of the LiMAx test were related with these scores and to critical postintervention LiMAx values., Results: LiMAx values correlated strongly with MELD and ALBI scores before the intervention and reflected the change in liver function, as shown by an increase in scores after the intervention. Notably, LiMAx values decreased during the intervention. AUC analysis for patients at risk of reaching a critical liver level after the intervention showed a cutoff value of 186μg/kg/h., Conclusions: The LiMAx test may be a valuable tool in liver ablation for both peri-interventional monitoring of liver function and preintervention risk assessment.

Fuel usage is an important catalyst for socio-economic development and human well-being. Human activities have resulted in significant increases in emissions from biomass burning (BB) and fossil fuel (FF) combustion which have significantly adversely affected human, ecosystem, and planetary health in this era of the Anthropocene. Sanjiaolongwan Maar Lake (SJLW), as a typical crater lake, uniquely receives atmospheric deposition from long-distance transport, and thus, its sediments reflect environmental change and human impacts on a broad scale. In this study, the concentrations and compositions of combustion products, including polycyclic aromatic compounds (PACs, i.e., polycyclic aromatic hydrocarbons (PAHs) and their oxygenated (OPAHs) and nitrogen heterocyclic derivatives (AZAs)) and black carbon (BC and its constituents char and soot), in SJLW over the past 400 years were investigated. The results showed that the PACs and soot concentrations and fluxes in SJLW have rapidly increased since 1950. The concentrations of the total PACs increased ~4 times after the 1950s. Such a fast increase is consistent with the rapid industrialization after the establishment of the People's Republic of China (PRC), which has further accelerated beginning with the implementation of the reform and opening up policy of the PRC in 1978. Moreover, the variations in the compositions of PACs, as well as the decrease in the char/soot ratio, demonstrate a transition in energy usage from BB to FF combustion. The decrease in the benzo[e]pyrene/benzo[a]pyrene ratio indicated an increase in local emissions (because of increasing industrialization in northeast China). The temporal profile of perylene concentrations, fluxes, and perylene/5-ring PAHs ratios strongly suggest that perylene mainly originated from non-pyrogenic sources. The records of PACs and BC in SJLW offer valuable perspectives on human impacts and provide important references for the start of the Anthropocene., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Severe paresis of the contralesional upper extremity is one of the most common and debilitating post-stroke impairments. The need for cost-effective high-intensity training is driving the development of new technologies, which can complement and extent conventional therapies. Apart from established methods using electromechanical devices, immersive virtual reality (iVR) systems hold promise to provide cost-efficient high-intensity arm training., Objective: We investigated whether iVR-based arm training yields at least equivalent effects on upper extremity function as compared to an electromechanically assisted training in stroke patients with severe arm paresis., Methods: 52 stroke patients with severe arm paresis received a total of ten daily group therapy sessions over a period of three weeks, which consisted of 20 min of conventional therapy and 20 min of either electromechanically assisted (ARMEOSpring ® ) or iVR-based (CUREO ® ) arm training. Changes in upper extremity function was assessed using the Action Research Arm Test (ARAT) and user acceptance was measured with the User Experience Questionnaire (UEQ)., Results: iVR-based training was not inferior to electromechanically assisted training. We found that 84% of patients treated with iVR and 50% of patients treated with electromechanically assisted arm training showed a clinically relevant improvement of upper extremity function. This difference could neither be attributed to differences between the groups regarding age, gender, duration after stroke, affected body side or ARAT scores at baseline, nor to differences in the total amount of therapy provided., Conclusion: The present study results show that iVR-based arm training seems to be a promising addition to conventional therapy. Potential mechanisms by which iVR unfolds its effects are discussed., Competing Interests: BS is now employed at Hocoma AG; no relationship existed at the time of the design or execution of this study. TS-W is shareholder of Cureosity. TS-W was neither involved in data acquisition nor in statistical analyses. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lülsdorff, Junker, Studer, Wittenberg, Pickenbrock and Schmidt-Wilcke.)

Importance: For their proliferation within red blood cells, malaria parasites depend on a functional electron transport chain (ETC) within their mitochondrion, which is the target of several antimalarial drugs. Here, we have used gene disruption to identify a patatin-like phospholipase, Pf PNPLA2, as important for parasite replication and mitochondrial function in Plasmodium falciparum . Parasites lacking Pf PNPLA2 show defects in their ETC and become hypersensitive to mitochondrion-targeting drugs. Furthermore, Pf PNPLA2-deficient parasites show differences in the composition of their cardiolipins, a unique class of phospholipids with key roles in mitochondrial functions. Finally, we demonstrate that parasites devoid of Pf PNPLA2 have a defect in gametocyte maturation, underlining the importance of a functional ETC for parasite transmission to the mosquito vector., Competing Interests: The authors declare no conflict of interest.

Understanding encoded languages, such as written script or Morse code, requires nonlexical and lexical processing components that act in a parallel and interactive fashion. Decoding written script-as for example in reading-is typically very fast, making the investigation of the lexical and nonlexical components and their underlying neural mechanisms challenging. In the current study, we aimed to accomplish this problem by using Morse code as a model for language decoding. The decoding of Morse code is slower and thus allows a better and more fine-grained investigation of the lexical and nonlexical components of language decoding. In the current study, we investigated the impact of various components of nonlexical decoding of Morse code using magnetoencephalography. For this purpose, we reconstructed the time-frequency responses below 40 Hz in brain regions significantly involved in Morse code decoding and word comprehension that were identified in a previous study. Event-related reduction in beta- and alpha-band power were found in left inferior frontal cortex and angular gyrus, respectively, while event-related theta-band power increase was found at frontal midline. These induced oscillations reflect working-memory encoding, long-term memory retrieval as well as demanding cognitive control, respectively. In sum, by using Morse code and MEG, we were able to identify a cortical network underlying language decoding in a time- and frequency-resolved manner., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Abstract: Sensitivity to pain shows a remarkable interindividual variance that has been reported to both forecast and accompany various clinical pain conditions. Although pain thresholds have been reported to be associated to brain morphology, it is still unclear how well these findings replicate in independent data and whether they are powerful enough to provide reliable pain sensitivity predictions on the individual level. In this study, we constructed a predictive model of pain sensitivity (as measured with pain thresholds) using structural magnetic resonance imaging-based cortical thickness data from a multicentre data set (3 centres and 131 healthy participants). Cross-validated estimates revealed a statistically significant and clinically relevant predictive performance (Pearson r = 0.36, P < 0.0002, R2 = 0.13). The predictions were found to be specific to physical pain thresholds and not biased towards potential confounding effects (eg, anxiety, stress, depression, centre effects, and pain self-evaluation). Analysis of model coefficients suggests that the most robust cortical thickness predictors of pain sensitivity are the right rostral anterior cingulate gyrus, left parahippocampal gyrus, and left temporal pole. Cortical thickness in these regions was negatively correlated to pain sensitivity. Our results can be considered as a proof-of-concept for the capacity of brain morphology to predict pain sensitivity, paving the way towards future multimodal brain-based biomarkers of pain., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background: People with human immunodeficiency virus (PWH) have an increased risk of chronic lung diseases and chronic inflammation. We aimed to investigate if inflammatory markers and monocyte activation are associated with faster lung function decline in PWH., Methods: We included 655 PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study. Eligible participants were aged ≥25 years and had 2 spirometries separated by >2 years. Inflammatory markers (interleukin [IL]-1β, IL-2, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ) were measured at baseline by Luminex, and soluble CD14 and soluble CD163 by enzyme-linked immunosorbent assay. Using linear mixed models, we investigated whether elevated cytokine levels were associated with faster lung function decline., Results: The majority of PWH were males (85.2%) with undetectable viral replication (95.3%). We found a faster decline in forced expiratory volume in 1 second (FEV1) in PWH with elevated IL-1β and IL-10, with an additional decline of 10.3 mL/year (95% confidence interval [CI], 2.1-18.6; P = .014) and 10.0 mL/year (95% CI, 1.8-18.2; P = .017), respectively. We found no interaction between smoking and IL-1β or IL-10 on FEV1 decline., Conclusions: Elevated IL-1β and IL-10 were independently associated with faster lung function decline in PWH, suggesting that dysregulated systemic inflammation may play a role in the pathogenesis of chronic lung diseases., Competing Interests: Potential conflicts of interest. R. F. T. has received a travel grant from Gilead. J. V. has received personal fees from ALK, AstraZeneca, Boehringer-Ingelheim, Chiesi, GSK, and Teva for advising/presenting. K. M. K. has received personal fees for data and safety monitoring board activities from Nuvaira and Organicell and for consulting from Allergan/AbbVie. S. D. N. has received a research grant from the Novo Nordisk Foundation. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Myasthenia gravis (MG) affects individuals as a chronic autoimmune disease for many years. Commonly, chronic diseases significantly reduce the patients' quality of life. Aiming to improve the future quality of life in MG, this study assessed the factors impacting quality of life. As gender-specific medicine is becoming increasingly important, this study also focused on understanding gender differences in the outcome of MG., Methods: The study is a combined monocentric, retrospective and prospective database analysis of patient records based on 2,370 presentations of 165 patients with clinically, serologically and/or electrophysiologically confirmed MG over an observation period of up to 47 years. The data collection included the following parameters: antibody status, disease severity, age, medication use, gender, and disease duration. In addition, a prospective survey was conducted on the quality of life using the Myasthenia gravis-specific 15-item Quality of Life scale (MG-QoL15) and on the activities of daily living using the MG-specific Activities of Daily Living scale (MG-ADL)., Results: Of the 165 patients, 85 were male (51.5%) and 80 were female (48.5%). The remaining baseline characteristics (e.g. age and antibody status) were consistent with other myasthenia gravis cohorts. A high body mass index (BMI) (p = 0.005) and a high disease severity (p < 0.001) were significantly associated with lower disease-specific quality of life. Additionally, the quality of life in women with MG was significantly reduced compared to male patients (19.7 vs. 13.0 points in the MG-QoL15, p = 0.024). Gender differences were also observable in terms of the period between initial manifestation and initial diagnosis and women were significantly more impaired in their activities of daily living (MG-ADL) than men (4.8 vs. 3.0 points, p = 0.032)., Conclusion: Women with MG had significantly poorer disease specific quality of life compared to men as well as patients with a higher BMI. In order to improve the quality of life, gender-specific medicine and further investigation regarding a modification of the quality of life by lowering the BMI are essential and necessary., Trial Registration: Study approval by the Ethics Committee of the University Medical Center Göttingen was granted (number 6/5/18)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Dissolved organic matter (DOM) contributes to forest C cycling. We assessed temporal variability, sources, and transformations of DOM during four years in a tropical montane forest with the help of stable C isotope ratios (δ 13 C values). We measured δ 13 C values of DOM in rainfall (RF), throughfall (TF), stemflow (SF), litter leachate (LL), soil solutions at the 0.15 and 0.30 m depths (SS15, SS30), and streamflow (ST) with TOC-IRMS. The δ 13 C values of DOM did not vary seasonally. We detected an event with a high δ 13 C value likely attributable to black carbon from local pasture fires. The mean δ 13 C values of DOM outside the event decreased in the order, RF (-26.0 ± 1.3‰) > TF (-28.7 ± 0.3‰) > SF (-29.2 ± 0.2‰) > LL (-29.6 ± 0.2‰) because of increasing leaching of C-isotopically light compounds. The higher δ 13 C values of DOM in SS15 (-27.8 ± 1.0‰), SS30 (-27.6 ± 1.1‰), and ST (-27.9 ± 1.1‰) than in the above-ground solutions suggested that roots and root exudates are major belowground DOM sources. Although in DOM the C/N ratios correlated with the δ 13 C values when all solutions were considered, this was not the case for SS15, SS30, and ST alone. Thus, the δ 13 C values of DOM provide an additional tool to assess the sources and turnover of DOM.

Precise motor timing requires the ability to flexibly adapt one's own movements with respect to changes in the environment. Previous studies suggest that the correction of perceived as compared to non-perceived timing errors involves at least partially distinct brain networks. The dorsolateral prefrontal cortex (dPFC) has been linked to the correction of perceived timing errors and evidence for a contribution of the ventrolateral PFC (vPFC) specifically to the correction of non-perceived errors exists. The present study aimed at clarifying the functional contribution of the left vPFC for the correction of timing errors by adopting high-definition transcranial direct current stimulation (HD-tDCS). Twenty-one young healthy volunteers synchronized their right index finger taps with respect to an isochronous auditory pacing signal. Perceivable and non-perceivable step-changes of the metronome were interspersed, and error correction was analyzed by means of the phase-correction response (PCR). In subsequent sessions anodal and cathodal HD-tDCS was applied to the left vPFC to establish a brain-behavior relationship. Sham stimulation served as control condition. Synchronization accuracy as well as error correction were determined immediately prior to and after HD-tDCS. The analysis suggests a detrimental effect of cathodal HD-tDCS distinctively on error correction in trials with perceived timing errors. The data support the significance of the left vPFC for error correction in the temporal domain but contradicts the view of a role in the correction of non-perceived errors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The clinical significance of Stenotrophomonas maltophilia in patients with COPD is poorly understood. We aimed to determine whether a lower respiratory tract culture positive for S. maltophilia in COPD patients was independently associated with increased risk of death and hospitalisation for exacerbation of COPD., Methods: An observational cohort study following outpatients with COPD in Eastern Denmark between 2010 and 2018, with a follow-up period of five years. Presence of S. maltophilia was treated as a time-varying exposure, where patients were considered exposed at the time of the first isolation of S. maltophilia from the lower respiratory tract. The hazard ratio (HR) of death and hospitalisation for acute exacerbations of COPD was assessed using a Cox proportional hazards regression., Results: Of the total 22,689 patients 459 (2.0%) had a lower respiratory sample positive for S. maltophilia. A total of 7,649 deaths (S. maltophilia positive: 243 (52.9%) and S. maltophilia negative: 7,406 (34.4%)) and 24,912 hospitalisations for exacerbation of COPD (S. maltophilia positive: 1,100 in 459 patients and S. maltophilia negative: 23,821 in 22,230 patients) were registered during the study period. We found that a lower respiratory tract culture positive for S. maltophilia was associated with both increased mortality: HR 3.3 (95% CI 2.6-4.3), and hospitalisation for exacerbation of COPD: HR 3.4 (95% CI 2.8-4.1)., Conclusions: A lower respiratory tract culture positive for S. maltophilia in COPD patients was associated with a substantially increased mortality and hospitalisation for exacerbation of COPD. Randomised controlled trials are proposed to determine whether S. maltophilia should be the target of antibiotic treatment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: It remains unclear whether long-term non-invasive ventilation (LT-NIV) for patients with chronic obstructive pulmonary disease (COPD) improves survival and reduces admissions as results from randomized trials are inconsistent. We aim to determine whether LT-NIV initiated after an admission with acute hypercapnic respiratory failure (AHRF) can affect survival and admission rate in COPD patients., Methods: A randomized controlled open-label trial, allocating patients with COPD to LT-NIV or standard of care immediately after an admission with AHRF treated with acute NIV. LT-NIV was aimed to normalize PaCO 2 using high-pressure NIV., Results: The study was discontinued before full sample size due to slow recruitment. 28 patients were randomized to LT-NIV and 27 patients to standard of care. 42% of patients had a history of ≥ 2 admissions with AHRF. Median IPAP was 24 cmH 2 O (IQR 20-28). The primary outcome, time to readmission with AHRF or death within 12 months, did not reach significance, hazard ratio 0.53 (95% CI 0.25-1.12) p  = 0.097. In a competing risk analysis, adjusted for history of AHRF, the odds ratio for AHRF within 12 months was 0.30 (95% CI 0.11-0.87) p  = 0.024. The LT-NIV group had less exacerbations (median 1 (0-1) vs 2 (1-4) p  = 0.021) and readmissions with AHRF (median 0 (0-1) vs 1 (0-1) p  = 0.016)., Conclusion: The risk of the primary outcome, time to readmission with AHRF or death within 12 months was numerically smaller in the LT-NIV group, however, did not reach significance. Nevertheless, several secondary outcome analyses like risk of AHRF, number of episodes of AHRF and exacerbations were all significantly reduced in favour of high-pressure LT-NIV, especially in patients with frequent AHRF., Competing Interests: KLA reports support of the study by TrygFonden and The Danish Lung Association’s Research Fund. No other author has competing interests to declare., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without asthma despite limited knowledge of its effects and side effects. We evaluated if treatment with promethazine had a lower risk of harmful outcome., Methods: Nationwide retrospective cohort study of Danish specialist diagnosed outpatients with COPD treated with promethazine or an active comparator (melatonin). Patients with collection of promethazine or melatonin were propensity score matched 1:1. The primary outcome was a composite of severe COPD exacerbations and death from all causes analyzed by Cox proportional hazards regression. We performed an interaction analysis for comorbid asthma., Results: In our registry of 56,523 patients with COPD, 5,661 collected promethazine ( n  = 3,723) or melatonin ( n  = 1,938). A cohort of 3,290 promethazine- or melatonin-treated patients matched 1:1 was available for the primary analysis.Within 1-year patients treated with promethazine were at higher risk of the primary outcome than matched controls with a Hazard Ratio (HR) of 1.42 (CI 1.27-1.58, p  < 0.0001). Similarly, the risk of death was higher for promethazine-treated patients (HR 1.53, CI 1.32-1.77, p  < 0.0001). An interaction analysis for comorbid asthma showed no interaction between comorbid asthma and the likelihood of a primary outcome when collecting promethazine ( p  = 0.19). Adjusted Cox analysis on the entire population indicated a further increased risk with more promethazine (HR for primary outcome among patients collecting ≥ 400 promethazine tablets/year=2.15, CI 1.94-2.38, p <0.0001)., Conclusions: Promethazine-treated patients with COPD had a concerning excess risk of a composite outcome of severe exacerbations and death from all causes compared to melatonin., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Inhaled corticosteroids (ICSs) are associated with an increased risk of pneumonia among patients with chronic obstructive pulmonary disease (COPD). The introduction of extrafine particle ICS has aimed to improve the distribution of medicine in the airways by altering deposition within the lungs, potentially affecting efficacy and side effects. It remains unclear if extrafine particle ICS administration alters the risk of pneumonia compared with standard particle size ICS., Methods: An observational cohort study including all Danish COPD outpatients receiving ICS from 2010 to 2017. The primary outcome was pneumonia hospitalisation in the different ICS particle dosing regimens. The primary analysis was an adjusted Cox proportional hazards model. For sensitivity analysis, a subgroup analysis of patients receiving spray devices was done. Further, we created a propensity score matched cohort, in which we matched for the same covariates as adjusted for in the main analysis., Results: A total of 35 691 patients were included of whom 1471 received extrafine particle ICS. Among these patients, 4657 were hospitalised due to pneumonia. Patients with COPD receiving extrafine particle ICS had a lower risk of hospitalisation due to pneumonia compared with patients receiving standard particle size ICS in our primary analysis (HR 0.75; 95% CI 0.63 to 0.89; p=0.002), subgroup analysis (HR 0.54; 95% CI 0.45 to 0.65; p<0.0001) and the propensity-matched population (HR 0.72; 95% CI 0.60 to 0.87; p=0.0006)., Interpretation: The use of extrafine particle ICS administration was associated with a lower risk of pneumonia hospitalisation in patients with COPD compared with those who received standard size treatment., Competing Interests: Competing interests: The authors declare that there are no conflicts of interest regarding this article. However, to ensure full transparency, we disclose the following potential conflicts of interest. ASJ, BB, CKH, CR, HKJ, JE, JGH, TW, J-USJ, PS and ZBH declare no potential conflicts of interest. RS has received support for congress fees and travel expenses from Abbort. TSIngebrigtsen is a member of the Danish Society of Anesthesiology’s scientific advisory board. TSItenov is involved in Astra Zenica’s advisory board for biological treatment of severe asthma. TB-S has received consulting fees from GSK and Sanofi Pasteur. Received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer, Sanofi Pasteur and GSK. Received support for attending meetings and/or travel by Astra Zeneca. Participation on Data Safety Monitoring Board or Advisory Board for GSK and Sanofi Pasteur. Receipt of equipment, materials, drugs, medical writing, gifts or other services from GE., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is a lack of detailed epidemiological studies of finger fractures, the most common fracture of the upper extremity., Methods: Based on data of 21 341 finger fractures in the Swedish Fracture register, a national quality registry that collects data on all fractures, this study describes anatomical distribution, cause, treatment, age distribution, and result in terms of patient related outcome measures (PROMs)., Results: The most common finger fracture was of the base of the 5th finger, followed by the distal phalanx in the 4th finger. Open fractures were most common in the distal phalanges, especially in the 3rd finger. Intraarticular fractures were most frequent in the middle phalanges. Fall accidents was the most common cause of a fracture. The mean age at injury was 40 years (38 for men, 43 for women). 86% of finger fractures in adults were treated non-operatively. Men were more frequently operated than women. Finger fractures did not affect hand function or quality of life and there were no relevant differences in PROMs between fracture type, treatment, or sex., Conclusion: This study presents detailed information about the various types of finger fractures which can be used as point of reference in clinical work and for future studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alfort et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale: Steam equilibration overcomes the problem of the traditional measurements of H isotope compositions, which leave an arbitrary amount of adsorbed water in the sample, by controlling for the entire exchangeable H pool, including adsorbed water and hydroxyl-H. However, the use of steam equilibration to determine nonexchangeable stable H isotope compositions in environmental media (expressed as δ 2 H n values) by mathematically eliminating the influence of exchangeable H after sample equilibration with waters of known H-isotopic composition requires the knowledge of the equilibrium isotope fractionation factor between steam-H and exchangeable H of the sample (α ex-w ), which is frequently unknown., Methods: We developed a new method to determine the α ex-w values for clay minerals, topsoil clay fractions, and mica by manipulating the contributions of exchangeable H to the total H pool via different degrees of post-equilibration sample drying. We measured the δ 2 H values of steam-equilibrated mineral and soil samples using elemental analyzer-pyrolysis-isotope ratio mass spectrometry., Results: The α ex-w values of seven clay minerals ranged from 1.071 to 1.140, and those of 19 topsoil clay fractions ranged from 0.885 to 1.216. The α ex-w value of USGS57 biotite, USGS58 muscovite, and of cellulose was 0.965, 0.871, and 1.175, respectively. The method did not work for kaolinite, because its small exchangeable H pool did not respond to the selected drying conditions. Structurally different mineral groups such as two- and three-layer clay minerals or mica showed systematically different α ex-w values. The α ex-w value of the topsoil clay fractions correlated with the soil clay content (r = 0.63, P = 0.004), the local mean annual temperature (r = 0.68, P = 0.001), and the δ 2 H values of local precipitation (r = 0.72, P < 0.001), likely to reflect the different clay mineralogy under different weathering regimes., Conclusions: Our new α ex-w determination method yielded realistic results in line with the few previously published values for cellulose. The determined α ex-w values were similar to the widely assumed values of 1.00-1.08 in the literature, suggesting that the adoption of one of these values in steam equilibration approaches is appropriate., (© 2023 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Background: Chronic pain affects up to 20% of the population, impairs quality of life and reduces social participation. Previous research reported that pain-related perceived injustice covaries with these negative consequences. The current study probed whether chronic pain patients responded more strongly to disadvantageous social inequity than healthy individuals., Methods: We administered the Ultimatum Game, a neuroeconomic social exchange game, where a sum of money is split between two players to a large sample of patients with chronic pain disorder with somatic and psychological factors ( n = 102) and healthy controls ( n = 101). Anonymised, and in truth experimentally controlled, co-players proposed a split, and our participants either accepted or rejected these offers., Results: Chronic pain patients were hypersensitive to disadvantageous inequity and punished their co-players for proposed unequal splits more often than healthy controls. Furthermore, this systematic shift in social decision making was independent of patients' performance on tests of executive functions and risk-sensitive (non-social) decision making ., Conclusions: Our findings indicate that chronic pain is associated with anomalies in social decision making (compared to healthy controls) and hypersensitivity to social inequity that is likely to negatively impact social partaking and thereby the quality of life.

Introduction: According to the Public Healthcare Code, contributing to primary care is one of the pharmacist's key missions. Accessibility without appointment and the territorial network of pharmacies make the pharmacist an essential player in the management of unscheduled care, which remains an important gateway for users into the primary care system. This type of requests, daily in pharmacies, has not been yet the subject of a qualitative or quantitative evaluation. The Grand-Est Region, regrouping nearly 8% of French pharmacies, wanted to conduct a specific survey to quantify and assess the unscheduled care requests addressed to pharmacists on its territory., Methods: The survey by URPS Pharmacists and ARS Grand-Est was conducted by Tous Pour la Santé over a period of 12months from November 2020 to November 2021. Participation in the study was on a voluntary basis. The main objective of this study was to define the typology of unscheduled care requests addressed to the Region pharmacies and to characterize the responses provided., Results: One hundred and eighty-nine pharmacies (nearly 12% of Grand Est pharmacies, the participation rate could certainly have been higher if the study had not been conducted during the COVID-19 pandemic), representing 11,010 unscheduled care requests, took part in the survey. Despite the profession's massive desire to get involved in handling unscheduled care requests, the survey revealed a lack of specific training for pharmacists on this subject and an all-too-rare update from the AFGSU. User requests concern both daily healthcare needs and more specific chronic patients' needs. They evolve according to the profile of the applicant, the seasons, the days of the week and the type of pharmacy concerned. All ages are represented, including young adults. The average duration of care by the pharmacy team was 8minutes per request, even though in 20% of cases this did not lead to any delivery of product and in 11% of cases to no remuneration for the pharmacist., Conclusion: This survey confirmed the role of the pharmacist in responding to unscheduled care requests as a first-line actor and referral agent in the health system. The implementation of shared multiprofessional protocols, including first and foremost general practionners, and the recognition of the contribution of pharmacy teams would allow to define a framework to optimize the patient's journey through the healthcare system., (Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

The impact of local biodiversity loss on ecosystem functioning is well established, but the role of larger-scale biodiversity dynamics in the delivery of ecosystem services remains poorly understood. Here we address this gap using a comprehensive dataset describing the supply of 16 cultural, regulating and provisioning ecosystem services in 150 European agricultural grassland plots, and detailed multi-scale data on land use and plant diversity. After controlling for land-use and abiotic factors, we show that both plot-level and surrounding plant diversity play an important role in the supply of cultural and aboveground regulating ecosystem services. In contrast, provisioning and belowground regulating ecosystem services are more strongly driven by field-level management and abiotic factors. Structural equation models revealed that surrounding plant diversity promotes ecosystem services both directly, probably by fostering the spill-over of ecosystem service providers from surrounding areas, and indirectly, by maintaining plot-level diversity. By influencing the ecosystem services that local stakeholders prioritized, biodiversity at different scales was also shown to positively influence a wide range of stakeholder groups. These results provide a comprehensive picture of which ecosystem services rely most strongly on biodiversity, and the respective scales of biodiversity that drive these services. This key information is required for the upscaling of biodiversity-ecosystem service relationships, and the informed management of biodiversity within agricultural landscapes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Malnutrition is prevalent after stroke, particularly if post-stroke oropharyngeal dysphagia (OD) reduces nutritional intake. To further understand stroke-related malnutrition, a thorough nutritional assessment was performed in ischemic stroke patients with or without OD during sub-acute inpatient rehabilitation., Methods: In this exploratory, observational, cross-sectional, multi-center study in Germany (NTR6802), ischemic stroke patients with ( N = 36) or without ( N = 49) OD were age- and sex-matched to healthy reference subjects. Presence of (risk of) malnutrition (MNA-SF), blood concentration of stroke-relevant nutritional compounds and metabolites, nutritional intake, quality of life (EQ-5D-5L), and activities of daily living (Barthel index) were assessed., Results: More than half of the stroke patients displayed (risk of) malnutrition, with higher prevalence in patient with OD vs . without OD. Fasted blood concentrations of vitamins B1, B2, B6, A, D, and E, selenium, choline, coenzyme Q10, albumin, pre-albumin, transferrin, docosahexaenoic acid, and eicosapentaenoic acid were all lower in stroke patients compared to their matched healthy reference subjects, irrespective of OD status. Reported energy, macronutrient, and water intake were lower in stroke patients vs . healthy reference subjects. As expected, quality of life and activities of daily living scores were lower in stroke vs . healthy reference subjects, with OD scoring worse than non-OD patients., Discussion: This study shows that malnutrition is highly prevalent in sub-acute stroke patients during rehabilitation. Even though patients with OD were more likely to be malnourished, blood levels of specific nutritional compounds were similarly lower in stroke patients with or without OD compared to healthy reference subjects. Furthermore, subgroup analysis showed similarly lower blood levels of specific nutritional compounds in patients that are normal nourished vs . patients with (risk of) malnutrition. This might imply disease-specific changes in blood levels on top of overall protein-energy malnutrition. The results of the current study underline that it is important to screen for nutritional impairments in every stroke patient, either with or without OD., Competing Interests: NvW, CAvdB, DR, and ML are employees of Danone Nutricia Research. Employees of Danone were offered to participate in an employee share subscription program. MS has received fees for consultancy and seminar presentations for Danone Nutricia. The authors declare that this study was funded by Danone Nutricia Research (Utrecht, the Netherlands), which is the research and innovation organization behind the Specialized Nutrition division of Danone. Study design and conduct, data acquisition, analysis, and interpretation, the writing of this article, and the decision to submit it for publication, were joint efforts between the researchers from Danone Nutricia Research, St. Mauritius Therapieklinik (Meerbusch, Germany), and Fachklinik Rhein Ruhr (Essen, Germany)., (Copyright © 2023 van Wijk, Studer, van den Berg, Ripken, Lansink, Siebler and Schmidt-Wilcke.)

In Germany, nurses, physiotherapists and speech and language therapists follow a qualifying training for about 1,5 years to become respiratory therapists (RTs). With respect to neurological illness, RTs diagnose and treat disorders of respiration, cough and swallowing as well as a retention of tracheobronchial secretions. There is an increasing demand for RTs in neurology, in neurointensive care and in neurological and neurosurgical early rehabilitation. The certification of specialized centers for weaning in neurological and neurosurgical early rehabilitation was introduced by the German Society for Neurorehabilitation (DGNR) in 2021. As a certification criterion it includes the employment of a respiratory therapists. In neurological organizations treating critically and severely ill patients, RTs work at an important interdisciplinary intersection of physicians, nurses and therapists. RTs are qualified to train teams, patients and family caregivers and to establish care structures for critically and severely ill neurological patients. Due to the complexity of neurological illnesses RTs working in neurological institutions need specific qualification. Specific training for RTs in neurology and neurorehabilitation might improve care for critically and severely ill neurological patients. Further professionalization of RT in Germany requires standardizing curricula, a professional society for RTs and, finally, academization., Competing Interests: Martin Groß und Oliver Summ erhielten Honorare für Weiterbildungstätigkeiten für die Deutsche Gesellschaft für pflegerische Weiterbildung (DGpW)., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The clinical implication of a residual flexion deformity following surgery for scaphoid nonunion is unclear. Sixty-three patients who underwent scaphoid nonunion surgery were assessed after a mean of 7 years (range 5-10) to analyse the outcomes based on the presence of residual scaphoid deformity. Primary outcome was Disabilities of the Arm, Shoulder and Hand score. Secondary outcomes were Patient-Rated Wrist Evaluation score, wrist range of motion and strength. Patients were dichotomized to residual deformity or no deformity. Scaphoid deformity was calculated from CT scans based on the median difference between the height-length ratio of the operated versus the uninjured scaphoid. There were no differences between residual deformity ( n  = 33) and no deformity ( n  = 30) in any outcome variables, except for wrist extension which was slightly worse in the deformity group. The deformity group had a greater number of radiographic osteoarthritis, but all cases were mild, and osteoarthritis did not correlate to a worse outcome. We conclude that residual scaphoid deformity has no relevant negative impact on mid-term wrist function. Level of evidence: IV.

Unilateral neglect is a common cognitive syndrome after stroke, which is defined as a spatially specific unawareness of the contralesional space. The syndrome is caused by disruptions of attentional networks in the brain, which impair the patients' ability to direct attention towards the contralesional space. During recovery, patients often learn to compensate by voluntarily directing their attention to the neglected side at the expense of cognitive resources. In this study, we examined the impact of the complexity of visual input on free visual exploration behavior of unilateral neglect and apparently recovered patients. We asked whether increasing scene complexity would allow the detection of residual unilateral neglect in recovered patients by increasing the amount of cognitive resources needed for visual processing and limiting capacities for compensation. Using virtual reality, we analyzed the spatial distribution of gaze of unilateral neglect patients, patients who had, according to conventional diagnostics, recovered from the syndrome, stroke patients with no history of unilateral neglect, and age-matched healthy controls. We manipulated the complexity of an immersive virtual scene presented on head mounted displays. We identified the orientation bias towards the ipsilesional side as a sensitive and specific marker of unilateral neglect, which was present in unilateral neglect and recovered patients but absent in stroke patients with no history of unilateral neglect and controls. Increasing scene complexity exacerbated the orientation shift in unilateral neglect patients and revealed that three out of nine (33%) recovered patients had a high probability of suffering from residual unilateral neglect as estimated by a generalized linear model using the median horizontal gaze position as a predictor., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Workplace incivility is a workplace stressor with varying effects according to the status of the target and instigator. This study sought to examine veterinary staff's experiences of incivility from clients, co-workers and senior colleagues., Method: An online mixed-measures survey gathered data from UK veterinary staff (n = 252, primarily veterinarians and nurses). Quantitative scales were used to collect data on incivility frequency, burnout, mental health, job satisfaction, turnover intention and key coping responses. Qualitative data expanded on preferred coping strategies., Results: The impact of uncivil behaviour varied according to the source of the incivility and the status of the target. Senior colleague incivility predicted veterinarian turnover intention, whereas client incivility predicted burnout. Similarly, senior colleague incivility predicted job satisfaction for veterinary nurses. Seeking support was the most frequently reported coping strategy. The qualitative data illustrated strategies focused on calming the situation and management of self., Limitations: The data are based on self-reports and are subject to social desirability bias. The sample is limited to UK veterinary staff., Conclusion: Veterinary staff are at risk of experiencing incivility, with varying impacts across job roles and incivility sources. A proactive system approach to incivility is recommended, encompassing support and procedural changes., (© 2022 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Background: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma., Methods: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20-365 from study allocation and (ii) days alive and without exacerbation within days 20-365 from the study allocation., Discussion: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients., Trial Registration: ClinicalTrials.gov NCT03262142 . Registered on August 25, 2017., (© 2022. The Author(s).)

Malaria is responsible for hundreds of thousands of deaths every year. The lack of an effective vaccine and the global spread of multidrug resistant parasites hampers the fight against the disease and underlines the need for new antimalarial drugs. Central to the pathogenesis of malaria is the proliferation of Plasmodium parasites within human erythrocytes. Parasites invade erythrocytes via a coordinated sequence of receptor-ligand interactions between the parasite and the host cell. Posttranslational modifications such as protein phosphorylation are known to be key regulators in this process and are mediated by protein kinases. For several parasite kinases, including the Plasmodium falciparum glycogen synthase kinase 3 (PfGSK3), inhibitors have been shown to block erythrocyte invasion. Here, we provide an assessment of PfGSK3 function by reverse genetics. Using targeted gene disruption, we show the active gene copy, PfGSK3β, is not essential for asexual blood stage proliferation, although it modulates efficient erythrocyte invasion. We found functional inactivation leads to a 69% decreased growth rate and confirmed this growth defect by rescue experiments with wildtype and catalytically inactive mutants. Functional knockout of PfGSK3β does not lead to transcriptional upregulation of the second copy of PfGSK3. We further analyze expression, localization, and function of PfGSK3β during gametocytogenesis using a parasite line allowing conditional induction of sexual commitment. We demonstrate PfGSK3β-deficient gametocytes show a strikingly malformed morphology leading to the death of parasites in later stages of gametocyte development. Taken together, these findings are important for our understanding and the development of PfGSK3 as an antimalarial target., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This prospective longitudinal study aimed to analyse the effect of partial wrist denervation on patient-reported outcomes, quality of life and objective function in symptomatic wrist osteoarthritis during the first year after surgery. Sixty consecutive patients underwent an anterior and posterior interosseous neurectomy during 2018-2020. Disabilities of the Arm, Shoulder and Hand, Patient-Rated Wrist Evaluation, EuroQol-5D-3L, pain at rest and on load, and objective function were assessed preoperatively and 3, 6 and 12 months postoperatively. Generalized estimating equations were used to analyse the effect on the outcome variables. Disabilities of the Arm, Shoulder and Hand, Patient-Rated Wrist Evaluation and pain scores improved significantly postoperatively with no decline over time, but no patient reported outcome measure reached the minimal clinically important difference. Quality of life, strength and range of motion did not improve. We found no complications. Seventeen patients needed further surgery during the study period. More studies are needed to evaluate whether denervation is truly effective or not. Level of evidence: II.

This prospective longitudinal study of 80 patients analysed the effect of preoperative pain catastrophizing, anxiety, depression and sense of coherence on the Disabilities of the Arm, Shoulder and Hand, Patient-Rated Wrist Evaluation, quality of life, grip strength and range of motion during the first year after salvage surgery for wrist osteoarthritis. Generalized estimating equations were used to analyse the effect of the psychological factors on the outcome variables. Pain catastrophizing or a tendency for anxiety preoperatively had a strong negative impact on postoperative Disabilities of the Arm, Shoulder and Hand and Patient-Rated Wrist Evaluation. Anxiety also predicted a lower postoperative quality of life, whereas pain catastrophizing had a negative impact on grip strength. Sense of coherence did not influence the outcome. Level of evidence: II.

Cardiovascular diseases are common in patients with chronic obstructive pulmonary disease (COPD). Clot formation and resolution secondary to systemic inflammation may be a part of the explanation. The aim was to determine whether biomarkers of clot formation (products of von Willebrand Factor formation and activation) and clot resolution (product of fibrin degeneration) during COPD exacerbation predicted major cardiovascular events (MACE). The cohort was based on clinical data and biobank plasma samples from a trial including patients admitted with an acute exacerbation of COPD (CORTICO-COP). Neo-epitope biomarkers of formation and the activation of von Willebrand factor (VWF-N and V-WFA, respectively) and cross-linked fibrin degradation (X-FIB) were assessed using ELISAs in EDTA plasma at the time of acute admission, and analyzed for time-to-first MACE within 36 months, using multivariable Cox proportional hazards models. In total, 299/318 participants had samples available for analysis. The risk of MACE for patients in the upper quartile of each biomarker versus the lower quartile was: X-FIB: HR 0.98 (95% CI 0.65-1.48), VWF-N: HR 1.56 (95% CI 1.07-2.27), and VWF-A: HR 0.78 (95% CI 0.52-1.16). Thus, in COPD patients with an acute exacerbation, VWF-N was associated with future MACE and warrants further studies in a larger population.

Background: Even with high standards of acute care and neurological early rehabilitation (NER) a substantial number of patients with neurological conditions still need mechanical ventilation and/or airway protection by tracheal cannulas when discharged and hence home-based specialised intensive care nursing (HSICN). It may be possible to improve the home care situation with structured specialized long-term neurorehabilitation support and following up patients with neurorehabilitation teams. Consequently, more people might recover over an extended period to a degree that they were no longer dependent on HSICN., Methods: This healthcare project and clinical trial implements a new specialised neurorehabilitation outreach service for people being discharged from NER with the need for HSICN. The multicentre, open, parallel-group RCT compares the effects of one year post-discharge specialized outpatient follow-up to usual care in people receiving HSICN. Participants will randomly be assigned to receive the new form of healthcare (intervention) or the standard healthcare (control) on a 2:1 basis. Primary outcome is the rate of weaning from mechanical ventilation and/or decannulation (primary outcome) after one year, secondary outcomes include both clinical and economic measures. 173 participants are required to corroborate a difference of 30 vs. 10% weaning success rate statistically with 80% power at a 5% significance level allowing for 15% attrition., Discussion: The OptiNIV-Study will implement a new specialised neurorehabilitation outreach service and will determine its weaning success rates, other clinical outcomes, and cost-effectiveness compared to usual care for people in need for mechanical ventilation and/or tracheal cannula and hence HSICN after discharge from NER., Trial Registration: The trial OptiNIV has been registered in the German Clinical Trials Register (DRKS) since 18.01.2022 with the ID DRKS00027326 ., (© 2022. The Author(s).)

Specialized centers for weaning in neurological and neurosurgical early rehabilitation can be certified by the German Society for Neurorehabilitation (DGNR) since 1 October 2021. The certification criteria are indicators for structure and process quality and for treatment results for weaning of neurological patients from mechanical ventilation. In Germany these patients are treated in departments for neurological and neurosurgical early rehabilitation in acute care hospitals as well as in specialized rehabilitation hospitals. Acknowledging this diversity of care, certification is possible for both kinds of institutions. Certification is granted by the DGNR in cooperation with TÜV Rheinland as the certification authority, analogous to the certification of stroke units. Institutions apply for certification by sending all necessary documents to the TÜV Rheinland. Afterwards auditors of the TÜV Rheinland (lead auditor) and the DGNR (medical speciality auditor) visit the institution on site. The results of this visit are reported to the certification committee of the DGNR, which in turn recommends or declines certification. The certification of centers for weaning in neurological and neurosurgical early rehabilitation is an important step towards defining neurorespiratory care and the role of the neurologist for intensive care and weaning in Germany. Thereby, the interdisciplinary dialogue between pneumologists, anesthesiologists, and neurologists is fostered. Also, the dialogue on treatment capacities and strategies with healthcare politicians, health insurances, and patient associations is facilitated., (© 2021. The Author(s).)

Introduction: Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired responses., Methods: Prospective cohort study including adults with chronic pulmonary diseases and healthcare personnel as controls (1:1). Blood was sampled at inclusion, 3 weeks, 2 and 6 months after first vaccination. We reported antibody concentrations as geometric means with 95% CI of receptor binding domain (RBD)-IgG and neutralising antibody index of inhibition of ACE-2/RBD interaction (%). A low responder was defined as neutralising index in the lowest quartile (primary outcome) or RBD-IgG <225 AU/mL plus neutralising index <25% (secondary outcome), measured at 2 months. We tested associations using Poisson regression., Results: We included 593 patients and 593 controls, 75% of all had neutralising index ≥97% at 2 months. For the primary outcome, 34.7% of patients (n=157/453) and 12.9% of controls (n=46/359) were low responders (p<0.0001). For the secondary outcome, 8.6% of patients (n=39/453) and 1.4% of controls (n=5/359) were low responders (p<0.001). Risk factors associated with low responder included increasing age (per decade, adjusted risk ratio (aRR) 1.17, 95% CI 1.03 to 1.32), Charlson Comorbidity Index (per point) (aRR 1.15, 95% CI 1.05 to 1.26), use of prednisolone (aRR 2.08, 95% CI 1.55 to 2.77) and other immunosuppressives (aRR 2.21, 95% CI 1.65 to 2.97)., Discussion: Patients with chronic pulmonary diseases established functional humoral responses to vaccination, however lower than controls. Age, comorbidities and immunosuppression were associated with poor immunological responses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aimed to assess the outcomes after simple trapeziectomy and trapeziectomy with ligament reconstruction and/or tendon interposition based on data in the Swedish national healthcare quality registry for hand surgery (HAKIR). Six-hundred and fifty thumbs were included, and 265 were assessed up to 12 months after operation. There was significant and clinically relevant improvement in patient-reported measures (pain on load, pain on motion without load, pain at rest, stiffness, weakness, and ability to perform activities of daily living and the Quick Disabilities of the Arm, Shoulder and Hand score) and objective measures (strength and thumb mobility) at 3 and 12 months for all procedures. The use of the abductor pollicis longus tendon had better improvement in some respects compared with the use of flexor carpi radialis or extensor carpi radialis tendons. However, overall, the use of a tendon adjuncts yielded no better outcomes than simple trapeziectomy. Level of evidence: III.

Background and Purpose: Patients with a corticobasal syndrome (CBS) present a rare form of atypical parkinsonism characterized by asymmetric clinical symptoms and progressive motor and nonmotor impairment, such as apraxia, alien limb phenomenon, aphasia, myoclonus, dystonia, and cognitive impairment. At early stages, clinical differentiation between CBS and idiopathic Parkinson's disease (IPD) can be challenging., Methods: Using high-resolution T1-weighted images and voxel-based morphometry (VBM), we sought to identify disease-specific patterns of brain atrophy in a small sample of CBS and IPD patients at early stages of disease. We acquired MR images of 17 patients diagnosed with CBS and compared them with MR images of 17 subjects affected by IPD. Images were preprocessed and analyzed using VBM., Results: When compared to each other, the CBS and IPD patients of our cohort showed differences in regional gray and white matter volume depending on the diagnosis, specifically in the superior longitudinal fascicle., Conclusions: In our small patients' group, VBM was able to detect changes in regional gray and white matter volume between patients affected by CBS and patients with IPD as early as 1.5-2 years after the onset of the first motor symptoms., (© 2022 American Society of Neuroimaging.)