Background Age-associated deterioration of the immune system contributes to a chronic low-grade inflammatory state known as "inflammaging" and is implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD). Whether changes in the tissue environment caused by circulatory factors associated with aging may alter the innate immune response is unknown. Monocyte-derived macrophages (Mo-MCYRILLIC CAPITAL LETTER EFs) infiltrating the brain alongside microglia are postulated to play a modulatory role in LOAD and both express triggering receptor expressed on myeloid cells 2 (TREM2). Apolipoprotein E (APOE) acts as a ligand for TREM2, and their role in amyloid beta (A beta) clearance highlights their importance in LOAD. However, the influence of the patient's own milieu (autologous serum) on the synthesis of TREM2 and APOE in infiltrating macrophages remains unknown. Objectives To functionally assess patient-specific TREM2 and APOE synthesis, we designed a personalized assay based on Mo-MCYRILLIC CAPITAL LETTER EFs using monocytes from LOAD patients and matched controls (CO). We assessed the influence of each participant's own milieu, by examining the effect of short- (1 day) and long- (10 days) term differentiation of the cells in the presence of the donor ' s autologous serum (AS) into M1-, M2- or M0-macrophages. Additionally, sex differences and A beta-uptake ability in short- and long-term differentiated Mo-MCYRILLIC CAPITAL LETTER EFs were assessed. Results We showed a time-dependent increase in TREM2 and APOE protein levels in LOAD- and CO-derived cells. While AS did not differentially modulate TREM2 compared to standard fetal calf serum (FCS), AS decreased APOE levels in M2 macrophages but increased levels in M1 macrophages. Interestingly, higher levels of TREM2 and lower levels of APOE were detected in female- than in male- LOAD patients. Finally, we report decreased A beta-uptake in long-term differentiated CO- and LOAD-derived cells, particularly in APOE epsilon 4(+) carriers. Conclusions We demonstrate for the first time the suitability of a personalized Mo-MCYRILLIC CAPITAL LETTER EF cell culture-based assay for studying functional TREM2 and APOE synthesis in a patient's own aged milieu. Our strategy may thus provide a useful tool for future research on diagnostic and therapeutic aspects of personalized medicine.

Background Suicidality, ranging from passive suicidal thoughts to suicide attempt, is common in major depressive disorder (MDD). However, relatively little is known about patient, illness and treatment characteristics in those with co-occurring MDD and suicidality, including the timing of and factors associated with the offset, continuation or reemergence of suicidality. Here, we present the background, rationale, design and hypotheses of the Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D) study, an investigator-initiated, observational study, funded by Janssen-Cilag GmbH.Methods/ResultsOASIS-D is an eight-site, six-month, cohort study of patients aged 18-75 hospitalized with MDD. Divided into three sub-studies and patient populations (PPs), OASIS-D will (i) systematically characterize approximately 4500 consecutively hospitalized patients with any form of unipolar depressive episode (PP1), (ii) evaluate the validity of the clinical diagnosis of moderate or severe unipolar depressive episode with the Mini-International Neuropsychiatric Interview (M.I.N.I.) and present suicidality (at least passive suicidal thoughts) present >= 48 h after admission with the Sheehan-Suicide Tracking Scale (S-STS), assessing also predictors of the diagnostic concordance/discordance of MDD in around 500 inpatients (PP2), and (iii) characterize and prospectively follow for 6 months 315 inpatients with a research-verified moderate or severe unipolar depressive episode and at least passive suicidal thoughts >= 48 h after admission, evaluating treatment and illness/response patterns at baseline, hospital discharge, 3 and 6 months. Exploratory objectives will describe the association between the number of days with suicidality and utilization of outpatient and inpatient care services, and structured assessments of factors influencing the risk of self-injurious behavior without suicidal intent, and of continuous, intermittent or remitted suicidality during the 6-month observation period.ConclusionDespite their frequency and clinical relevance, relatively little is known about patient and treatment characteristics of individuals with MDD and suicidality, including factors moderating and mediating the outcome of both MDD and suicidality. Results of the OASIS-D study are hoped to improve the understanding of the frequency, correlates and 6-month naturalistic treatment and outcome trajectories of different levels of suicidality in hospitalized adults with MDD and suicidality.

Objective Topiramate is a repurposed first-line treatment for migraine prophylaxis. The aim of this systematic review and meta-analysis is to critically re-appraise the existing evidence supporting the efficacy and tolerability of topiramate.MethodsA systematic search in MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis as of August 13, 2022, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Randomized controlled trials in adult patients that used topiramate for the prophylactic treatment of migraine, with placebo as active comparator, were included. Two reviewers independently screened the retrieved studies and extracted all data. Outcomes of interest were the 50% responder rates, the reduction in monthly migraine days, and adverse events leading to treatment discontinuation. Results were pooled and meta-analyzed, with sensitivity analysis based on the risk of bias of the studies, the monthly migraine days at baseline, and the previous use of other prophylactic treatments. Certainty evidence was judged according to the GRADE framework.ResultsEight out of 10,826 studies fulfilled the inclusion/exclusion criteria, accounting for 2,610 randomized patients. Six studies included patients with episodic migraine and two with chronic migraine. Topiramate dose ranged from 50 to 200 mg/day, and all studies included a placebo arm. There was a high certainty that topiramate: 1) increased the proportion of patients who achieved a 50% responder rate in monthly migraine days, compared to placebo [relative risk: 1.61 (95% confidence interval (CI): 1.29-2.01); absolute risk difference: 168 more per 1,000 (95% CI: 80 to 278 more)]; 2) was associated with 0.99 (95% CI: 1.41-0.58) fewer migraine days than placebo; 3) and had a higher proportion of patients with adverse events leading to treatment discontinuation [absolute risk difference 80 patients more per 1,000 (95% CI: 20 to 140 more patients)].ConclusionsThere is high-quality evidence of the efficacy of topiramate in the prophylaxis of migraine, albeit its use poses a risk of adverse events that may lead to treatment discontinuation, with a negative effect on patient satisfaction and adherence to care.

Background Mechanical and morphological factors have both been described to influence the rate of pseudarthrosis in mandibular reconstruction. By minimizing mechanical confounders, the present study aims to evaluate the impact of bone origin at the intersegmental gap on osseous union.Methods Patients were screened retrospectively for undergoing multi-segment fibula free flap reconstruction of the mandible including the anterior part of the mandible and osteosynthesis using patient-specific 3D-printed titanium reconstruction plates. Percentage changes in bone volume and width at the bone interface between the fibula/fibula and fibula/mandible at the anterior intersegmental gaps within the same patient were determined using cone-beam computed tomography (CBCT). Additionally, representative samples of the intersegmental zones were assessed histologically and using micro-computed tomography (mu CT).Results The bone interface (p = 0.223) did not significantly impact the change in bone volume at the intersegmental gap. Radiotherapy (p < 0.001), time between CBCT scans (p = 0.006) and wound healing disorders (p = 0.005) were independent risk factors for osseous non-union. Preliminary analysis of the microstructure of the intersegmental bone did not indicate morphological differences between fibula-fibula and fibula-mandible intersegmental bones.Conclusions The bone interface at the intersegmental gap in mandibular reconstruction did not influence long-term bone healing significantly. Mechanical and clinical properties seem to be more relevant for surgical success.

Background The extent of resection of glioma is one of the most important predictors of the survival duration of patients after surgery. The presence of eloquent areas within or near a tumor often limits resection, as resection of these areas would result in functional loss and reduced quality of life. The aim of this randomized, triple-blind, sham-controlled study is to investigate the capability of repetitive navigated transcranial magnetic stimulation (rnTMS) over the primary motor cortex to facilitate the functional reorganization of the motor network.MethodsOne hundred forty-eight patients with tumors in movement-relevant areas will be included in this randomized, sham-controlled, bicentric, triple-blind clinical trial. Patients considered at high risk for postoperative motor deficits according to an initial nTMS assessment will receive inhibitory rnTMS at 1 Hz for 30 min followed by a short motor training of 10 min. Stimulation will be applied to the fiber endings of the corticospinal tract closest to the tumor based on individualized tractography. Stimulation will be performed twice daily for each 30 min for 5-28 days depending on the individually available time between study inclusion and surgery. The intervention is controlled by a sham stimulation group (1:1 randomization), where a plastic adapter will be placed on the coil. We expect a comparable or better motor status 3 months postoperatively as measured by the British Medical Research Council (BMRC) score for the affected upper extremity (non-inferiority) and a higher rate of gross total resections (superiority) in the rnTMS compared to the sham group.DiscussionThe generated reorganization of the brain's areas for motor function should allow a more extensive and safer removal of the tumor while preserving neurological and motor function. This would improve both survival and quality of life of our patients.

Background Breast cancer and cervical cancer are among the most common cancers in women in Germany. Early detection examinations such as mammography and the cervical smear test (Pap-test) have been shown to contribute to the reduction in the mortality and/or incidence of these cancers and can be utilised free of charge by women in certain age groups as part of national screening programmes. Analyses show that the use of health services varies regionally, especially when comparing the federal states of the former German Democratic Republic (GDR, Eastern Germany) and the Federal Republic of Germany (FRG, Western Germany). This study investigated to what extent the utilisation of mammography examinations and Pap-tests by women differs in federal states of former GDR and FRG.MethodsFor this purpose, we analysed data from the nationwide health survey GEDA14/15 conducted by the Robert Koch Institute (RKI) in 2014 and 2015. We calculated weighted proportions and compared attendance between eastern and western German states by a Chi-Square-test. Additionally, we conducted regression analysis to adjust for socio-economic status, living environment and place of birth.Results2,772 female participants aged 20-34 years were analysed for Pap-test attendance in the last two years and 4,323 female participants aged 50-69 years old were analysed for mammography screening attendance in the last two years. 50-69-year-old women in eastern German states were with 78.3% (95%-CI 75.3%, 81.2%) more likely to attend mammography screening than in western Germany with 73.4% (95%-CI 71.8%, 74.9%). Pap-test uptake was statistically significantly higher in the East of Germany with 83.3% (95%-CI 79.6%, 87.1%) compared to 77.5% (95%-CI 75.8%, 79.3%) in the West of Germany. This relationship was robust to adjusting for socio-economic status, living environment and place of birth.ConclusionsCultural influences and socialization in the GDR might explain the higher utilisation of these cancer screening examinations at least to some extent. This could have many reasons, for example a higher health awareness through education or a possible greater trust in medical structures and the associated higher compliance of women. These hypotheses should be further explored to increase the uptake of screening examinations by women in Germany.

Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p < 5 x 10(-8)). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.26; 95%-CI: 1.20-1.31; p < 9.6 x 10(-27)) and IRX1 (rs12653958, OR: 1.17; 95%-CI: 1.12-1.22, p < 4.8 x 10(-13)) as candidate causal genes through integration of gene expression in disease relevant tissues. We further identified a likely causal detrimental effect of low fasting glucose levels on RP risk (r(G) = -0.21; p-value = 2.3 x 10(-3)), and systematically highlighted drug repurposing opportunities, like the antidepressant mirtazapine. Our results provide the first robust evidence for a strong genetic contribution to RP and highlight a so far underrated role of alpha 2A-adrenoreceptor signalling, encoded at ADRA2A, as a possible mechanism for hypersensitivity to catecholamine-induced vasospasms.

COVID-19 is associated with various neurological symptoms. Serum neurofilament light chain (sNfL) is a robust marker for neuroaxonal injury. Recent studies have shown that elevated levels of sNfL are associated with unfavorable outcome in COVID-19 patients. However, neuroaxonal injury is rare in COVID-19, and renal dysfunction and hypoxia, both of which are known in severe COVID-19, can also increase sNfL levels. Thus, the meaning and mechanisms of sNfL elevation in COVID-19 patients remain unclear. We evaluated sNfL levels in 48 patients with COVID-19 (mean age = 63 years) and correlated them to clinical outcome, the form of oxygen therapy, and creatinine. Levels of sNfL were age adjusted and compared with normal values and z-scores. COVID-19 patients treated with nasal cannula had normal sNfL levels (mean sNfL = 19.6 pg/ml) as well as patients with high-flow treatment (mean sNfL = 40.8 pg/ml). Serum NfL levels were statistically significantly higher in COVID-19 patients treated with mechanical ventilation on intensive care unit (ICU) (mean sNfL = 195.7 pg/ml, p < 0.01). There was a strong correlation between sNfL elevation and unfavorable outcome in COVID-19 patients (p < 0.01). However, serum creatinine levels correlated directly and similarly with sNfL elevation and with unfavorable outcome in COVID-19 patients (p < 0.01). Additionally, multivariate analysis for serum creatinine and sNfL showed that both variables are jointly associated with clinical outcomes. Our results identify renal dysfunction as an important possible confounder for sNfL elevation in COVID-19. Thus, serum creatinine and renal dysfunction should be strongly considered in studies evaluating sNfL as a biomarker in COVID-19.

Background The effect of leadership support for adherence to infection control and prevention (IPC) measures has been demonstrated. To expand this support, a target group-specific educational study for chief medical officers (CMO) was implemented and its influence on IPC indicators was investigated.MethodsA controlled cohort study was conducted between 2018 and 2019. The intervention based on an initial workshop, an e-learning course, and a final meeting. Participants' activities involving IPC management were surveyed. Consumption of alcohol hand rub (AHR) and incidence density of hospital-associated (HA) Clostridioides difficile-associated infections (CDI) were analyzed.ResultsEight percent of 360 CMOs invited participated in the initial workshop; 70% of those participants registered for the online course. Overall, 43% completed the post-intervention questionnaire, in which 85% of respondents reported increased collaboration with relevant stakeholders. The pre-intervention median AHR consumption was higher in the intervention group than in the control group. Both groups showed an increase (38.6 (interquartile range (IQR) 33.6; 45.0) to 41.9 ml/patient day (PD) (IQR 35.0; 56.6) and 33.4 (IQR 28.3; 40.8) to 35.8 ml/ PD (IQR 31.6; 43.2), respectively). Pre-intervention median HA CDI cases were lower in the intervention group than in the control group. Both groups reported a decrease (0.22 (IQR 0.17; 0.33) to 0.19 cases/1000 PD (IQR 0.15; 0.26) and 0.32 (IQR 0.2; 0.48) to 0.22 cases/1000 PD (IQR 0.11; 0.33), respectively).ConclusionMultimodal IPC training of CMOs is worthwhile and can lead to changes in IPC-relevant cooperation in hospitals. IPC training of hospital management should be further intensified.

Background Carcinoid heart disease (CHD) caused by neuroendocrine tumours (NET) is associated with an increased morbidity and mortality due to valvular dysfunction and right sided heart failure. The present study aimed to assess the prevalence and one-year-incidence of CHD in NET patients. Tumour characteristics, laboratory measurements, and echocardiographic findings were evaluated to identify predictors of CHD manifestation.MethodsThe study was an investigator-initiated, monocentric, prospective trial. Patients with NET without previously diagnosed CHD were included and underwent comprehensive gastroenterological and oncological diagnostics. Echocardiographic examinations were performed at baseline and after one year.ResultsForty-seven NET patients were enrolled into the study, 64% of them showed clinical features of a carcinoid syndrome (CS). Three patients presented with CHD at baseline and three patients developed cardiac involvement during the follow-up period corresponding to a prevalence of 6% at baseline and an incidence of 6.8% within one year. Hydroxyindoleacetic acid (5-HIAA) was identified to predict the occurrence of CHD (OR, 1.004; 95% CI, 1.001-1.006 for increase of 5-HIAA), while chromogranin A (CgA), and Kiel antigen 67 (Ki 67%) had no predictive value. Six patients with CHD at twelve-month follow-up revealed a tendency for larger right heart diameters and increased values of myocardial performance index (MPEI) at baseline compared to NET patients.ConclusionThe prevalence at baseline and one-year-incidence of CHD was 6-7%. 5-HIAA was identified as the only marker which predict the development of CHD.

Background The PROMIS Preference score (PROPr) is a new health state utility (HSU) score that aims to comprehensively incorporate the biopsychosocial model of health and apply favorable psychometric properties from the descriptive PROMIS system to HSU measurements. However, minimal evidence concerning comparisons to the EQ-5D-3L and the PROPr's capability to differentiate clinical severity are available. Therefore, the aim of this study was to compare the PROPr to the EQ-5D-3L in terms of scale agreement, ceiling/floor effects, distribution, construct validity, discriminatory power, and relative efficiency (RE) in terms of the Oswestry Disability Index (ODI) for patients with low back pain (LBP).Methods We used intra-class correlation coefficients (ICC) and Bland-Altman plots to compare the PROPr and EQ-5D-3L with regared to scale agreement in a cross-sectional routine sample of LBP patients. For distribution, we used the Pearson's coefficient for skewness and for ceiling/floor effects, a 15%-top/bottom threshold. For convergent validity, we used Pearson's correlation coefficients. For known-groups validity, we applied a linear regression with interaction terms (predictors sex, age, and ODI level) and an analysis of variance (ANOVA). For discriminatory power, we calculated the effect size (ES) using Cohen's d and the ratio of the area under the receiver-operating characteristics curves (AUROC-ratio = AUROC(PROPr)/AUROC(EQ-5D-3L)). RE was measured using the ratio of F-values (RE = F-PROPr/FEQ-5D-3L).Results Of 218 LBP patients, 50.0% were female and the mean age was 61.8 years. The mean PROPr (0.20, 95%CI: 0.18; 0.22) and EQ-5D-3L scores (0.55, 95%CI: 0.51; 0.58) showed low agreement (d = 0.35, p < 0.001; ICC 0.27, 95%CI: -0.09; 0.59). The PROPr's distribution was positively skewed, whereas the EQ-5D-3L's was negative. Neither tool showed ceiling/floor effects, but all EQ-5D-3L dimensions did. Pearson correlation was r = 0.66 (95%CI: 0.58; 0.73). Differences were invariant to sex and age but not to ODI severity: ESEQ-5D-3L > ES(PROPr )and RE < 1 in higher ODI severity; ESEQ-5D-3L < ESPROPr and RE > 1 in lower ODI severity. AUROC-ratios did not show significant differences in terms of ODI severity.Conclusions All PROPr and EQ-5D-3L biopsychosocial dimensions of health showed impairment in LPB patients. The capability of EQ-5D-3L and PROPr to differentiate ODI levels depends on ODI severity. Joint application of both tools may provide additional information.

Background A significant and growing portion of the global burden of diseases is caused by neurological disorders. Tele-neurology has the potential to improve access to health care services and the quality of care, particularly in rural and underserved areas. The economic evaluation of the stepped wedge randomised controlled trial NeTKoH aims to ascertain the cost-effectiveness and cost-utility regarding the effects of a tele-neurologic intervention in primary care in a rural area in Germany.MethodsThis protocol outlines the methods used when conducting the trial-based economic evaluation of NeTKoH. The outcomes used in our economic analysis are all prespecified endpoints of the NeTKoH trial. Outcomes considered for the cost-utility and cost-effectiveness analyses will be quality-adjusted life years (QALYs) derived from the EQ-5D-5L, proportion of neurologic problems being solved at the GP's office (primary outcome), hospital length-of-stay and number of hospital stays. Costs will be prospectively collected during the trial by the participating statutory health insurances, and will be analysed from a statutory health insurance perspective within the German health care system. This economic evaluation will be reported complying with the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist.DiscussionThis within-trial economic evaluation relaying the costs and outcomes of an interdisciplinary tele-consulting intervention will provide high-quality evidence for cost-effectiveness and policy implications of a tele-neurological programme, including the potential for application in other rural areas in Germany or other jurisdictions with a comparable health system.Trial registrationGerman Clinical Trials Register (DRKS00024492), date registered: September 28, 2021.

The fundamental value of universal nomenclatural systems in biology is that they enable unambiguous scientific communication. However, the stability of these systems is threatened by recent discussions asking for a fairer nomenclature, raising the possibility of bulk revision processes for “inappropriate” names. It is evident that such proposals come from very deep feelings, but we show how they can irreparably damage the foundation of biological communication and, in turn, the sciences that depend on it. There are four essential consequences of objective codes of nomenclature: universality, stability, neutrality, and transculturality. These codes provide fair and impartial guides to the principles governing biological nomenclature and allow unambiguous universal communication in biology. Accordingly, no subjective proposals should be allowed to undermine them.

Biological invasions are a major threat to biodiversity, ecosystem functioning and nature's contributions to people worldwide. However, the effectiveness of invasive alien species (IAS) management measures and the progress toward achieving biodiversity targets remain uncertain due to limited and nonuniform data availability. Management success is usually assessed at a local level and documented in technical reports, often written in languages other than English, which makes such data notoriously difficult to collect at large geographic scales. Here we present the first European assessment of how managers perceive trends in IAS and the effectiveness of management measures to mitigate biological invasions. We developed a structured questionnaire translated into 18 languages and disseminated it to local and regional managers of IAS in Europe. We received responses from 1928 participants from 41 European countries, including 24 European Union (EU) Member States. Our results reveal substantial efforts in IAS monitoring and control, with invasive plants being the primary focus. Yet, there is a general perception of an increase in the numbers, occupied areas, and impacts of IAS across environment and taxonomic groups, particularly plants, over time. This perceived increase is consistent across both EU and non-EU countries, with respondents from EU countries demonstrating more certainty in their responses. Our results also indicate a lack of data on alien vertebrates and invertebrates, reflecting a need for more targeted monitoring and knowledge sharing between managers and policymakers and between countries. Overall, our study suggests that Europe's current strategies are insufficient to substantially reduce IAS by 2030 and hence to meet the Kunming-Montreal Global Biodiversity Framework target.

Amphibians are commonly occurring inhabitants of most lentic freshwater ecosystems, yet their global populations are in alarming decline. Ponds in particular play a crucial role in supporting amphibian biodiversity. In this study, we identified the main drivers influencing amphibian species richness by conducting a comprehensive ecological characterization in 201 ponds across seven European countries spanning a large latitudinal and longitudinal gradient. The amphibian species richness in each of these ponds was assessed using environmental DNA metabarcoding on water samples. The relative influence of climatic, local abiotic and biotic, and land use variables on variation in species richness across ponds was quantified using boosted regression trees. Our results suggest that local factors, particularly chlorophyll-a concentration, but also pond area and depth, are the main drivers of amphibian richness, together with climatic variables such as annual mean precipitation and temperature. The highest richness was observed in low-nutrient, fishless, intermediate-sized, shallow ponds, located in warmer regions with higher precipitation rates. These potential drivers of amphibian richness should be considered in the planning and implementation of amphibian conservation and management actions.

Fluorescence detection of DNA and RNA G-quadruplexes (G4s) is a very efficient strategy to assess not only the existence and prevalence of cellular G4s but also their relevance as targets for therapeutic interventions. Among the fluorophores used to this end, turn-on probes are the most interesting since their fluorescence is triggered only upon interaction with their G4 targets, which ensures a high sensitivity and selectivity of detection. We reported on a series of twice-as-smart G4 probes, which are both smart G4 ligands (whose structure is reorganized upon interaction with G4s) and smart fluorescent probes (whose fluorescence is turned on upon interaction with G4s). The fine mechanistic details behind the excellent properties of the best prototype N-TASQ remain to be deciphered: to investigate this, we report here on the synthesis and studies of two analogues, TzN-TASQ and AlkN-TASQ, and on a careful analysis of their G4-interacting properties, investigated both in vitro and in silico. Our results show that fine-tuning their constitutive structural elements allows for increasing the efficiency of both their ‘off’ (i. e., a conformation with a low fluorescence) and ‘on’ states (i. e., a conformation with a high fluorescence), which opens interesting ways for the design of more efficient fluorogenic G4 probes.

Currently, most peripheral nerve injuries are incurable mainly due to excessive reactive oxygen species (ROS) generation in inflammatory tissues, which can further exacerbate localized tissue injury and cause chronic diseases. Although promising for promoting nerve regeneration, stem cell therapy still suffers from abundant intrinsic limitations, mainly including excessive ROS in lesions and inefficient production of growth factors (GFs). Biomaterials that scavenge endogenous ROS and promote GFs secretion might overcome such limitations and thus are being increasingly investigated. Herein, firstly reported as specific ROS scavenging agents and paracrine stimulators, gold nanoparticles (GNPs) were incorporated in the chitosan/polyvinyl alcohol hydrogel networks. The GNPs/hydrogel composite can support the survival of mesenchymal stem cells (MSCs) with excellent expansion efficiency and protect MSCs in a simulated ROS microenvironment, decreasing the intracellular ROS levels and simultaneously enhancing cell viability. Moreover, biodegradable scaffolds, along with MSCs, were implanted into sciatic nerve defects in a rat model to show good application value in vivo. Our work demonstrated that the GNPs/hydrogel shows great promise in MSCs therapy for peripheral nerve injury with convincing biological evidence.

Severe cases of COVID-19 are associated with immune responses that lead to a surge in inflammatory molecules, resulting in multi-organ failure and death. This significant increase in inflammatory factors is triggered by viral proteins. Open reading frame 8 (ORF8) has received particular attention as a unique accessory protein of SARS-CoV-2. In a previous study, we have examined the role of unconventionally released ORF8 during cytokine storm associated with SARS-CoV-2 infection. Here, after mass spectrometry analysis and gene knockout/knockdown in cell/hamster models, we further discovered that Yip1 interacting factor homolog B (YIF1B) directly translocates unglycosylated ORF8 into vesicles that mediate cargo transport; specifically, the α4 helix of YIF1B interacts with the β8 sheet. Blocking ORF8 unconventional secretion via YIF1B knockdown attenuates inflammation and yields reduced mortality. Our study suggests that YIF1B directs ORF8 translocation into an unconventional secretion pathway, which has significant implications for the pathogenesis and treatment of COVID-19.

Higher education for sustainable development (HESD) can be challenging for university teachers. The normative core of the concept may be perceived as a contrast to the ideal of objective knowledge production which has dominated Western academia for a long time. As university teachers concurrently fulfil different roles, they can be exposed to sometimes incompatible expectations. In this paper, we present role conflicts university teachers may face when implementing ESD in their courses. For this, we used sociological role theory as a framework to analyse data from a qualitative interview study conducted with university teachers. The results show three typical role conflicts: 1. the “personal stance” conflict, 2. the “practice what you preach” conflict, and 3. the “lethargic institution” conflict. In order to support university teachers in coping with these conflicts, we recommend reflecting on ESD-related values and ambiguities in university classes, reinforcing professional development for university teachers in ESD, especially in the field of emotional competence, and the implementation of Whole Institution Approaches.

The average age of our population is increasing, resulting in a high incidence of chronic degenerative knee pathologies. Several treatment options, including surgical procedures are available to help mitigate these pathologies. However, the percentage of subjects with chronic post-surgical knee pain is still estimated at 16-20%. Neuromodulation techniques such as spinal cord stimulation and dorsal root ganglion stimulation (DRGS) are treatment options for subjects with chronic knee pain. The evidence for peripheral nerve stimulation (PNS) is minimal due to a limited number of neuromodulation systems capable of targeting the distal part of the lower limbs. This study aimed to investigate the safety and efficacy externally powered PNS systems for the treatment of chronic intractable knee pain targeting the saphenous nerve. Patients suffering from chronic intractable post-surgical knee pain received landmark-guided peripheral nerve stimulation of the branches of the saphenous nerve. All implants were performed with an externally powered PNS system to avoid lead migration as a result of cross-joint lead positions tunneling towards an Implantable Pulse Generator to the trunk. Data were collected retrospectively. Subject-reported outcome was measured via numerical rating scale values on a 10-point scale measuring pain intensity at rest and in motion. Additional data were collected for the subjects treated at the Charite location, including quality of life with the SF-36 form, quality of sleep with the Pittsburgh Sleep Quality Index and mood states with the short form of the General Depression Scale. Thirty-three patients received direct to permanent implant, landmark-guided peripheral nerve stimulation of the saphenous nerve branches. Six (18.2%) subjects reported non-sufficient initial benefit from the therapy and were explanted. Two subjects were explanted due to wound infections. The total study population reported included 25 patients. These subjects reported significant improvements related to pain, quality of life, mood quality, and quality of sleep. Additionally, subjects were able to reduce their opioid medication significantly after PNS therapy. Externally powered PNS at the saphenous nerve branches is a straightforward, selective and safe technique for patients with chronic knee pain. The landmark-guided implantation technique is less invasive than classical neuromodulation techniques such as spinal cord or DRGS and complication rates remain low. Short-term results are promising and show considerable reductions in pain scores and opioid intake. Long-term results are pending.