Astroglial glucose uptake determines brain FDG-PET alterations and metabolic connectivity during healthy aging in mice.

PURPOSE: 2-Fluorodeoxyglucose-PET (FDG-PET) is a powerful tool to study glucose metabolism in mammalian brains, but cellular sources of glucose uptake and metabolic connectivity during aging are not yet understood. METHODS: Healthy wild-type mice of both sexes (2-21 months of age) received FDG-PET and cell sorting after in vivo tracer injection (scRadiotracing). FDG uptake per cell was quantified in isolated microglia, astrocytes and neurons. Cerebral FDG uptake and metabolic connectivity were determined by PET. A subset of mice received measurement of blood glucose levels to study associations with cellular FDG uptake during aging. RESULTS: Cerebral FDG-PET signals in healthy mice increased linearly with age. Cellular FDG uptake of neurons increased between 2 and 12 months of age, followed by a strong decrease towards late ages. Contrarily, FDG uptake in microglia and astrocytes exhibited a U-shaped function with respect to age, comprising the predominant cellular source of higher cerebral FDG uptake in the later stages. Metabolic connectivity was closely associated with the ratio of glucose uptake in astroglial cells relative to neurons. Cellular FDG uptake was not associated with blood glucose levels and increasing FDG brain uptake as a function of age was still observed after adjusting for blood glucose levels. CONCLUSION: Trajectories of astroglial glucose uptake drive brain FDG-PET alterations and metabolic connectivity during aging.

Protein persulfidation in plants: mechanisms and functions beyond a simple stress response.

Posttranslational modifications (PTMs) can modulate the activity, localization and interactions of proteins and (re)define their biological function. Understanding how changing environments can alter cellular processes thus requires detailed knowledge about the dynamics of PTMs in time and space. A PTM that gained increasing attention in the last decades is protein persulfidation, where a cysteine thiol (-SH) is covalently bound to sulfane sulfur to form a persulfide (-SSH). The precise cellular mechanisms underlying the presumed persulfide signaling in plants are, however, only beginning to emerge. In the mitochondrial matrix, strict regulation of persulfidation and H2S homeostasis is of prime importance for maintaining mitochondrial bioenergetic processes because H2S is a highly potent poison for cytochrome c oxidase. This review summarizes the current knowledge about protein persulfidation and corresponding processes in mitochondria of the model plant Arabidopsis. These processes will be compared to the respective processes in non-plant models to underpin similarities or highlight apparent differences. We provide an overview of mitochondrial pathways that contribute to H2S and protein persulfide generation and mechanisms for H2S fixation and de-persulfidation. Based on current proteomic data, we compile a plant mitochondrial persulfidome and discuss how persulfidation may regulate protein function.

Regional desynchronization of microglial activity is associated with cognitive decline in Alzheimer's disease.

BACKGROUND: Microglial activation is one hallmark of Alzheimer disease (AD) neuropathology but the impact of the regional interplay of microglia cells in the brain is poorly understood. We hypothesized that microglial activation is regionally synchronized in the healthy brain but experiences regional desynchronization with ongoing neurodegenerative disease. We addressed the existence of a microglia connectome and investigated microglial desynchronization as an AD biomarker. METHODS: To validate the concept, we performed microglia depletion in mice to test whether interregional correlation coefficients (ICCs) of 18 kDa translocator protein (TSPO)-PET change when microglia are cleared. Next, we evaluated the influence of dysfunctional microglia and AD pathophysiology on TSPO-PET ICCs in the mouse brain, followed by translation to a human AD-continuum dataset. We correlated a personalized microglia desynchronization index with cognitive performance. Finally, we performed single-cell radiotracing (scRadiotracing) in mice to ensure the microglial source of the measured desynchronization. RESULTS: Microglia-depleted mice showed a strong ICC reduction in all brain compartments, indicating microglia-specific desynchronization. AD mouse models demonstrated significant reductions of microglial synchronicity, associated with increasing variability of cellular radiotracer uptake in pathologically altered brain regions. Humans within the AD-continuum indicated a stage-depended reduction of microglia synchronicity associated with cognitive decline. scRadiotracing in mice showed that the increased TSPO signal was attributed to microglia. CONCLUSION: Using TSPO-PET imaging of mice with depleted microglia and scRadiotracing in an amyloid model, we provide first evidence that a microglia connectome can be assessed in the mouse brain. Microglia synchronicity is closely associated with cognitive decline in AD and could serve as an independent personalized biomarker for disease progression.

The chemical composition and sources of road dust, and of tire and road wear particles-A review.

To gain better understanding of how the transition to electric vehicles affects road dust (RD) composition, and potential health and environmental risks, it is crucial to analyze the chemical composition of RD and identify its sources. Sources of RD include wear of tire tread (TT), brake wear (BW) and road wear (RW). A relevant component of RD are tire and road wear particles (TRWPs). This literature review compiles data on the chemical bulk composition of RD sources, RD in Asia, Europe and North America and TRWP as a RD component. The focus is on elements such as Cd, Co, Cr, Cu, Ni, Pb, V, and Zn. Although the comparability of global RD data is limited due to differences in sampling and analytical methods, no significant differences in the composition from Asia, Europe, and North America were found for most of the investigated elements studied, except for Cd, Co, and V. Sources of RD were analyzed using elemental markers. On average TT, BW, and RW contributed 3 %, 1 %, and 96 %, respectively. The highest concentrations of TT (9 %) and BW (2 %) were observed in the particle size fraction of RD ≤ 10 µm. It is recommended that these results be verified using additional marker compounds. The chemical composition of TRWPs from different sources revealed that (i) TRWPs isolated from a tunnel dust sample are composed of 31 % TT, 6 % BW, and 62 % RW, and (ii) test material from tire test stands show a similar TT content but different chemical bulk composition likely because e.g., of missing BW. Therefore, TRWPs from test stands need to be chemically characterized prior to their use in hazard testing to validate their representativeness.

Hotspots of Floating Plastic Particles across the North Pacific Ocean.

The pollution of the marine environment with plastic debris is expected to increase, where ocean currents and winds cause their accumulation in convergence zones like the North Pacific Subtropical Gyre (NPSG). Surface-floating plastic (>330 µm) was collected in the North Pacific Ocean between Vancouver (Canada) and Singapore using a neuston catamaran and identified by Fourier-transform infrared spectroscopy (FT-IR). Baseline concentrations of 41,600-102,700 items km-2 were found, dominated by polyethylene and polypropylene. Higher concentrations (factors 4-10) of plastic items occurred not only in the NPSG (452,800 items km-2) but also in a second area, the Papaha̅naumokua̅kea Marine National Monument (PMNM, 285,200 items km-2). This second maximum was neither reported previously nor predicted by the applied ocean current model. Visual observations of floating debris (>5 cm; 8-2565 items km-2 and 34-4941 items km-2 including smaller "white bits") yielded similar patterns of baseline pollution (34-3265 items km-2) and elevated concentrations of plastic debris in the NPSG (67-4941 items km-2) and the PMNM (295-3748 items km-2). These findings suggest that ocean currents are not the only factor provoking plastic debris accumulation in the ocean. Visual observations may be useful to increase our knowledge of large-scale (micro)plastic pollution in the global oceans.

Localization of four class I glutaredoxins in the cytosol and the secretory pathway and characterization of their biochemical diversification.

Class I glutaredoxins (GRXs) are catalytically active oxidoreductases and considered key proteins mediating reversible glutathionylation and deglutathionylation of protein thiols during development and stress responses. To narrow in on putative target proteins, it is mandatory to know the subcellular localization of the respective GRXs and to understand their catalytic activities and putative redundancy between isoforms in the same compartment. We show that in Arabidopsis thaliana, GRXC1 and GRXC2 are cytosolic proteins with GRXC1 being attached to membranes through myristoylation. GRXC3 and GRXC4 are identified as type II membrane proteins along the early secretory pathway with their enzymatic function on the luminal side. Unexpectedly, neither single nor double mutants lacking both GRXs isoforms in the cytosol or the ER show phenotypes that differ from wild-type controls. Analysis of electrostatic surface potentials and clustering of GRXs based on their electrostatic interaction with roGFP2 mirrors the phylogenetic classification of class I GRXs, which clearly separates the cytosolic GRXC1 and GRXC2 from the luminal GRXC3 and GRXC4. Comparison of all four studied GRXs for their oxidoreductase function highlights biochemical diversification with GRXC3 and GRXC4 being better catalysts than GRXC1 and GRXC2 for the reduction of bis(2-hydroxyethyl) disulfide. With oxidized roGFP2 as an alternative substrate, GRXC1 and GRXC2 catalyze the reduction faster than GRXC3 and GRXC4, which suggests that catalytic efficiency of GRXs in reductive reactions depends on the respective substrate. Vice versa, GRXC3 and GRXC4 are faster than GRXC1 and GRXC2 in catalyzing the oxidation of pre-reduced roGFP2 in the reverse reaction.

Influence of Silver Fiber Morphology on the Dose-Response Relationship and Enrichment in Daphnia magna Studied by Elemental Imaging with LA-ICP-TOF-MS.

This study aims to enhance the understanding of the environmental risks associated with nanomaterials, particularly nanofibers. Previous research suggested that silver fibers exhibit higher toxicity (EC50/48h 1.6-8.5 µg/L) compared to spherical silver particles (EC50/48h 43 µg/L). To investigate the hypothesis that toxicity is influenced by the morphology and size of nanomaterials, various silver nanofibers with different dimensions (length and diameter) were selected. The study assessed their toxicity toward Daphnia magna using the 48 h immobilization assay. The EC50 values for the different fibers ranged from 122 to 614 µg/L. Subsequently, the study quantified the uptake and distribution of two representative nanofibers in D. magna neonates by employing digestion and imaging mass spectrometry in the form of laser-ablation-ICP-MS. A novel sample preparation method was utilized, allowing the analysis of whole, intact daphnids, which facilitated the localization of silver material and prevented artifacts. The results revealed that, despite the similar ecotoxicity of the silver fibers, the amount of silver associated with the neonates differed by a factor of 2-3. However, both types of nanofibers were primarily found in the gut of the organisms. In conclusion, the findings of this study do not support the expectation that the morphology or size of silver materials affect their toxicity to D. magna.

Training the next generation of plastics pollution researchers: tools, skills and career perspectives in an interdisciplinary and transdisciplinary field.

Plastics pollution research attracts scientists from diverse disciplines. Many Early Career Researchers (ECRs) are drawn to this field to investigate and subsequently mitigate the negative impacts of plastics. Solving the multi-faceted plastic problem will always require breakthroughs across all levels of science disciplinarity, which supports interdisciplinary discoveries and underpins transdisciplinary solutions. In this context, ECRs have the opportunity to work across scientific discipline boundaries and connect with different stakeholders, including industry, policymakers and the public. To fully realize their potential, ECRs need to develop strong communication and project management skills to be able to effectively interface with academic peers and non-academic stakeholders. At the end of their formal education, many ECRs will choose to leave academia and pursue a career in private industry, government, research institutes or non-governmental organizations (NGOs). Here we give perspectives on how ECRs can develop the skills to tackle the challenges and opportunities of this transdisciplinary research field and how these skills can be transferred to different working sectors. We also explore how advisors can support an ECRs' growth through inclusive leadership and coaching. We further consider the roles each party may play in developing ECRs into mature scientists by helping them build a strong foundation, while also critically assessing problems in an interdisciplinary and transdisciplinary context. We hope these concepts can be useful in fostering the development of the next generation of plastics pollution researchers so they can address this global challenge more effectively.

Accelerated aging of tire and road wear particles by elevated temperature, artificial sunlight and mechanical stress - A laboratory study on particle properties, extractables and leachables.

Tire and road wear particles (TRWP) are generated in large quantity by automobile traffic on roads but their way of degradation in the environment is largely unclear. Laboratory experiments were performed on the effect of elevated temperature (simulating 2-3 years), sunlight exposure (simulating 0.5 years) and mechanical stress on the physical properties and chemical composition of TRWP and of cryo-milled tire tread (CMTT). No significant effects were observed of the applied mechanical stress on mean properties of pristine particles. After sunlight exposure up to 40 % in mass were lost from the TRWP, likely due to the loss of mineral incrustations from their surface. The chemical composition of TRWP and CMTT was characterized by determining 27 compounds, antioxidants (phenylene diamines), vulcanization agents (benzothiazoles and guanidines) and their transformation products (TPs). Extractables of TRWP (580-850 µg/g) were dominated by TPs, namely benzothiazolesulfonic acid (BTSA). CMTT showed much higher amounts of extractables (4600 µg/g) which were dominated by parent chemicals such as N-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylenediamine (6-PPD), diphenylguanidine (DPG) and mercaptobenzothiazole (MBT). Sunlight exposure affected the amount of extractables more strongly than elevated temperature, for TRWP (-45 % vs -20 %) and CMTT (-80 % vs -25 %) and provoked a clear shift from parent compounds to their TPs. After sunlight exposure extractables of TRWP were dominated by BTSA and DPG. Sunlight exposure drastically reduced the 6-PPD amount extracted from both, TRWP and CMTT (-93 %, -98 %), while its quinone (6-PPDQ) increased by around 1 % of the 6-PPD decrease, only. For many TPs, concentration in leachates were higher than in extracts, indicating ongoing transformation of their parent compounds during leaching. These results highlight that abiotic aging of TRWP leads to strong changes in their chemical composition which affect their particle properties and are of relevance for the environmental exposure to tire-related chemicals.

Results of an interlaboratory comparison for characterization of Pt nanoparticles using single-particle ICP-TOFMS.

This study describes an interlaboratory comparison (ILC) among nine (9) laboratories to evaluate and validate the standard operation procedure (SOP) for single-particle (sp) ICP-TOFMS developed within the context of the Horizon 2020 project ACEnano. The ILC was based on the characterization of two different Pt nanoparticle (NP) suspensions in terms of particle mass, particle number concentration, and isotopic composition. The two Pt NP suspensions were measured using icpTOF instruments (TOFWERK AG, Switzerland). Two Pt NP samples were characterized and mass equivalent spherical sizes (MESSs) of 40.4 ± 7 nm and 58.8 ± 8 nm were obtained, respectively. MESSs showed <16% relative standard deviation (RSD) among all participating labs and <4% RSD after exclusion of the two outliers. A good agreement was achieved between the different participating laboratories regarding particle mass, but the particle number concentration results were more scattered, with <53% RSD among all laboratories, which is consistent with results from previous ILC studies conducted using ICP-MS instrumentation equipped with a sequential mass spectrometer. Additionally, the capabilities of sp-ICP-TOFMS to determine masses on a particle basis are discussed with respect to the potential for particle density determination. Finally, because quasi-simultaneous multi-isotope and multi-element determinations are a strength of ICP-TOFMS instrumentation, the precision and trueness of isotope ratio determinations were assessed. The average of 1000 measured particles yielded a precision of below ±1% for intensity ratios of the most abundant Pt isotopes, i.e.194Pt and 195Pt, while the accuracy of isotope ratios with the lower abundant isotopes was limited by counting statistics.

Effects of Inpatient Rehabilitation in Leg Lymphedema: A Naturalistic Prospective Cohort Study With Intra-individual Control of Effects.

OBJECTIVE: To quantify therapy-attributable effects of a comprehensive inpatient rehabilitation program for lower limb lymphedema (LLL) and to compare the levels of health-related quality of life (HRQL) to population-based norms. DESIGN: Naturalistic prospective cohort study with intra-individual control of effects. SETTING: Rehabilitation hospital. PARTICIPANTS: Patients with LLL (N=67; 46 women). INTERVENTIONS: Comprehensive, multidisciplinary inpatient rehabilitation with 45-60 hours of therapy. MAIN OUTCOME MEASURES: Short Form 36 (SF-36) for HRQL, lymphedema-specific Freiburg Quality of Life Assessment for lymphatic disorders, Short Version (FLQA-lk), knee-specific Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL), and Symptom Checklist-90Standard (SCL-90S). Observed pre/post rehabilitation effects were individually corrected by subtracting the home waiting-time effects and expressed as standardized effect sizes (ESs) and standardized response means (SRMs). Score differences to norms were quantified by standardized mean differences (SMDs). RESULTS: Participants were on average aged 60.5 years, not yet obese, and had 3 comorbidities (n=67). The greatest improvement was in HRQL on the FLQA-lk with ES=0.767/SRM=0.718, followed by improvements in pain and function with ES/SRM=0.430-0.495 on the SF-36, FLQA-lk, and KOS-ADL (all P<.001). Vitality, mental health, emotional well-being, and interpersonal sensitivity improved most by ES/SRM=0.341-0.456 on all 4 measures (all P≤.003). Post rehabilitation scores were significantly higher than population norms on SF-36 bodily pain (SMD=1.140), vitality (SMD=0.886), mental health (SMD=0.815), and general health (SMD=0.444) (all P<.001), and comparable on the other scales. CONCLUSIONS: Those affected by LLL stages II and III benefited substantially from the intervention, attaining equal or higher levels of HRQL than expected compared with the general population norms. Multidisciplinary, inpatient rehabilitation should be recommended for LLL management.

Firms' responses to the COVID-19 pandemic.

The COVID-19 pandemic requires firms to adequately respond. In this study, we first explore in our empirical data how firms responded to the COVID-19 crisis and identify five tactical response types, operational, digitalization, financial, supportive, and organizational responses. Furthermore, our findings indicate that responses vary in scope; Some firms act on their own, while others engage in collaborations. Finally, we find that the response angle is different across firms, as some firms leverage potential and others primarily mitigate risk. Second, we follow an event study design to measure the financial implications of these responses. We find that responses to the COVID-19 pandemic generally entail a positive stock market reaction. Financial and digitalization responses, as well as risk mitigation responses, are consistently evaluated positively. We discuss our findings in context of different theoretical lenses, substantiating the emerging literature on the COVID-19 crisis, and the established literature on crisis response management.

Anaphylactic reaction to carboplatin diagnosed by skin testing-a reliable tool in platinum-based immediate-type hypersensitivity reactions.

Immediate-type hypersensitivity reactions (IHRs) to carboplatin (CA) are most commonly reported in ovarian cancer patients. A 54-year-old woman with stage IV melanoma suffering from metastasis in the entire right lower extremity was presented to our allergy outpatient clinic for diagnostic work-up due to an anaphylactic reaction with palmoplantar erythema, conjunctivitis along with facial erythema, and an incipient decrease in blood pressure during a chemotherapy regimen with dacarbazine and carboplatin upon re-administration. A subsequently carried out allergological work-up with skin testing (ST) revealed CA to be the culprit drug, whereas cisplatin (CI) was confirmed to be a safe alternative for the patient for following treatments. Here, we report a case of an IHR to carboplatin in a melanoma patient, with CI serving as a safe alternative diagnosed by skin testing.

MCU proteins dominate in vivo mitochondrial Ca2+ uptake in Arabidopsis roots.

Ca2+ signaling is central to plant development and acclimation. While Ca2+-responsive proteins have been investigated intensely in plants, only a few Ca2+-permeable channels have been identified, and our understanding of how intracellular Ca2+ fluxes is facilitated remains limited. Arabidopsis thaliana homologs of the mammalian channel-forming mitochondrial calcium uniporter (MCU) protein showed Ca2+ transport activity in vitro. Yet, the evolutionary complexity of MCU proteins, as well as reports about alternative systems and unperturbed mitochondrial Ca2+ uptake in knockout lines of MCU genes, leave critical questions about the in vivo functions of the MCU protein family in plants unanswered. Here, we demonstrate that MCU proteins mediate mitochondrial Ca2+ transport in planta and that this mechanism is the major route for fast Ca2+ uptake. Guided by the subcellular localization, expression, and conservation of MCU proteins, we generated an mcu triple knockout line. Using Ca2+ imaging in living root tips and the stimulation of Ca2+ transients of different amplitudes, we demonstrated that mitochondrial Ca2+ uptake became limiting in the triple mutant. The drastic cell physiological phenotype of impaired subcellular Ca2+ transport coincided with deregulated jasmonic acid-related signaling and thigmomorphogenesis. Our findings establish MCUs as a major mitochondrial Ca2+ entry route in planta and link mitochondrial Ca2+ transport with phytohormone signaling.

Identification of the Catalytically Dominant Iron Environment in Iron- and Nitrogen-Doped Carbon Catalysts for the Oxygen Reduction Reaction.

For large-scale utilization of fuel cells in a future hydrogen-based energy economy, affordable and environmentally benign catalysts are needed. Pyrolytically obtained metal- and nitrogen-doped carbon (MNC) catalysts are key contenders for this task. Their systematic improvement requires detailed knowledge of the active site composition and degradation mechanisms. In FeNC catalysts, the active site is an iron ion coordinated by nitrogen atoms embedded in an extended graphene sheet. Herein, we build an active site model from in situ and operando 57Fe Mössbauer spectroscopy and quantum chemistry. A Mössbauer signal newly emerging under operando conditions, D4, is correlated with the loss of other Mössbauer signatures (D2, D3a, D3b), implying a direct structural correspondence. Pyrrolic N-coordination, i.e., FeN4C12, is found as a spectroscopically and thermodynamically consistent model for the entire catalytic cycle, in contrast to pyridinic nitrogen coordination. These findings thus overcome the previously conflicting structural assignments for the active site and, moreover, identify and structurally assign a previously unknown intermediate in the oxygen reduction reaction at FeNC catalysts.

Mapping the Swiss Vaccine Supply Chain.

Objectives: The design of the supply chain determines how effectively any vaccination campaign can be operated. This case study of Switzerland's vaccine supply chain compares its design with public health objectives. It maps the vaccine supply chain in Switzerland as it was set up to handle the first shipments of Covid-19 vaccine in 2021 to enable a more holistic view of supply and demand flows. Recommendations are made to improve emergency logistics of vaccines in the future. Methods: Twenty-six semi-structured interviews with international and Swiss stake-holders were coded and analyzed to arrive at a description of planning and distribution processes. The vaccine supply chain network structure was mapped, linking upstream and downstream flows of material and information. The visualization of nodes and flows was combined with spatial information, including population data. The results are summarized in narrative form to support decision-makers across disciplines. Results: Despite adequate vaccine supply, abundant local endowments and high investment in infrastructure, the 2021 design of Switzerland's vaccine supply chain reduced the potential reach of target populations. The segmentation of catchment populations, collaboration between administrative units and better use of information on geolocation and material flows could have improved the speed and reach of vaccinations during the emergency response phase. Three recommendations are made for supply chain structures to support higher vaccination rates in the future. Conclusions: The visualization identifies design alternatives which could have improved vaccination rates under the prevailing conditions. A supply chain map provides public health officials with a shared view of the vaccine supply chain in order to better match supply with demand. The case study contributes to developed country studies. In order to improve public health outcomes in Switzerland, investments to secure supply, strong national endowments, and excellent infrastructure must be combined with optimized supply chain design.

Kinetic Diagnostics and Synthetic Design of Platinum Group Metal-Free Electrocatalysts for the Oxygen Reduction Reaction Using Reactivity Maps and Site Utilization Descriptors.

The experimental development of catalytically ever-more active platinum group metal (PGM)-free materials for the oxygen reduction reaction (ORR) at fuel cell cathodes has been until recently a rather empirical iteration of synthesis and testing. Here, we present how kinetic reactivity maps based on kinetic descriptors of PGM-free single-metal-site ORR electrocatalysts can help to better understand the origin of catalytic reactivity and help to derive rational synthetic guidelines toward improved catalysts. Key in our analysis are the catalytic surface site density (SD) and the catalytic turnover frequency (TOF) in their role as controlling kinetic parameters for the ORR reactivity of PGM-free nitrogen-coordinated single-metal M-site carbon (MNC) catalysts. SD-TOF plots establish two-dimensional reactivity maps. We also consider the ratio between SD and the total number of single-metal sites in the bulk, referred to as the site utilization factor, which we propose as another guiding parameter for optimizing the synthesis of MNC catalysts. Exemplified by two sets of FeNC, CoNC, and SnNC catalysts prepared using two distinctly different N- and C-precursor material classes (Zn-based zeolitic imidazolate frameworks and covalent polyaniline), we comparatively diagnose the intrinsic kinetic ORR parameters as well as structural, morphological, and chemical properties. From there, we derive and discuss possible synthetic guidelines for further improvements. Our approach can be extended to other families of catalysts and may involve kinetic performance data of idealized liquid-electrolyte cells as well as gas diffusion layer-type flow cells.

Cultural adaption and multicenter validation of the German version of the LYMPH-Q Upper Extremity Module.

OBJECTIVE: Upper extremity lymphedema is a burdensome disease with significant effects on quality of life, underscoring the importance of quality of life measures for this patient population. Only recently, the LYMPH-Q Upper Extremity Module, a new patient-reported outcome measure, was developed. The aim of the present study was to translate the LYMPH-Q Upper Extremity Module from English to German and perform a comprehensive validation. METHODS: Translation was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research best practice guidelines. To validate the German LYMPH-Q, a multicenter study was conducted. Internal consistency was determined using Cronbach's α. Reliability was assessed using the intraclass correlation coefficient. To analyze construct validity, the Pearson correlation coefficient between the LYMPH-Q, quickDASH (disabilities of the arm, shoulder, and hand), and short-form 36-item health survey was calculated. Responsiveness was assessed by comparing the pre- and postoperative LYMPH-Q scores in five patients who had undergone lymphatic reconstructive surgery. RESULTS: Validation was performed using a cohort of 65 patients. The internal consistency of the different domains was good to excellent (α, 0.87-0.97). The intraclass correlation coefficient ranged from 0.74 to 0.92. The domains of the LYMPH-Q correlated significantly with the corresponding domains of the short-form 36-item health survey and quickDASH. Construct validity was good, with 8 of 10 hypotheses confirmed. Significant improvements in function (46.4 ± 13.3 vs 77.8 ± 11.5; P = .03), symptoms (42.0 ± 10.7 vs 70.6 ± 11.6; P = .02), and psychological well-being (40.4 ± 14.6 vs 78.0 ± 17.3; P = .03) were observed after lymphatic reconstructive surgery. CONCLUSIONS: The German version of the LYMPH-Q Upper Extremity Module was shown to be conceptually equivalent to the original English version. It was shown to be a reliable and valid patient-reported outcome measure to assess the physical and psychological impairments in patients with upper extremity lymphedema.