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Malte Baldewig,1 Olaf Goldbaum,2 Christiane Richter-Landsberg,2 Andreas Weyland,1 Carsten Bantel1 1Department of Anesthesiology, Klinikum Oldenburg, Oldenburg, Germany; 2Molecular Neurobiology, Department of Neuroscience, University of Oldenburg, Oldenburg, Germany Purpose: Gabapentinoids are currently the mainstay of pharmacological treatments for patients with neuropathic pain. Little is known about the effects of this therapy on the integrity of neuronal networks, especially in patients with an already-damaged nervous system. Since gabapentinoids can worsen cognitive functions and recent studies have shown alterations in the brains of patients with neuropathic pain, it may be possible that these drugs have neurotoxic effects.Methods: Rat clonal PC12 pheochromocytoma (autonomic) and primary sensory dorsal-root ganglion (DRG) neurons from newborn Wistar rats were employed for this study. To mimic neuronal damage, cells were exposed to cytotoxins using either hydrogen peroxide (H2O2) or vincristine.Results: No direct cytotoxic effects were observed after incubating PC12 cells for 24 hours with increasing concentrations of gabapentin or pregabalin using MTT cytotoxicity assays. Even a 7-day incubation did not cause cellular damage. Furthermore, in preinjured PC12 and DRG neurons, neither gabapentin nor pregabalin prevented or enhanced the cytotoxic effects of H2O2 or vincristine after incubation for 24 hours and 7 days, respectively. Cell morphology and integrity of the cytoskeleton assessed by employing immunostaining of cytoskeletal proteins (α-tubulin, neurofilament L) remained intact and were not altered by gabapentinoids.Conclusion: Based on these results, gabapentinoids are unlikely to be neurotoxic in cultured autonomic (PC12) and sensory DRG cells, even when cells are preinjured. These results are of high clinical relevance, as it seems unlikely that the morphological changes recently observed in the brains of neuropathic pain patients are caused or worsened by gabapentinoids. Keywords: gabapentin, pregabalin, cytotoxicity, cytoskeleton, neuropathic pain

BackgroundMultiple stressors as well as health-and quality-impairing effects of strain in the nursing profession require the systematic acquisition of competence in dealing with these demands, starting at the stage of initial vocational training. This study investigates whether an instructional design, which merges didactic principles of nursing education with concepts and training measures from stress psychology, promotes the acquisition of stress coping competence more effectively than regular teaching on the relevant curricular field at nursing schools.MethodsThe quasi-experimental study design, based on the Solomon four-group plan, included 332 trainees in Germany. The assessment of stress coping competence at the beginning and at the end of the intervention provided a video-stimulated situational judgment test covering nursing-specific stressful situations. All were validated by field experts. Complementing group comparisons, regression analyses examined intervention effects at the individual level while controlling for other predictors of learning success.ResultsThe highest solution rates for the two basic dimensions of stress coping competence, i.e., (1) situation assessment and (2) strategy selection and justification, occurred in the treatment classes without a pretest. At the individual level, treatment effects were confirmed for the first dimension. Students with a migration background showed lower competence gains than other students.ConclusionThe instructional design and the competence test provide valuable foundations for promoting and for diagnosing coping skills. Nevertheless, subsequent studies should examine adaptive support for different learner groups. Furthermore, additional observational phases should focus on the deliberate practice of acquired coping strategies in the practical training settings of nursing education.

MAGUK p55 subfamily member 7, a part of the membrane palmitoylated protein subfamily, is an essential adapter that promotes epithelial cell polarity and has increasing significance in multiple cancers, including esophageal cancer, clear cell renal cell carcinoma, breast cancer, and pancreatic ductal adenocarcinoma. This paper aims to determine the effect of the MAGUK p55 subfamily member 7 in various tumor types using The Cancer Genome Atlas and Genotype-Tissue Expression database. A variety of software and web platforms, such as cBioPortal, GEPIA2, TIMER2, UALCAN, R, STRING, and DAVID, were used to obtain and analyze data. Notably, low expression of MAGUK p55 subfamily member 7 was observed in most cancers. In addition, low expression of MAGUK p55 subfamily member 7 predicted poor prognoses in cancer patients. Mutation was the most frequent genetic alteration type in MAGUK p55 subfamily member 7, with the phosphorylation sites identified as S412 and S490 in various cancers. Furthermore, expression of MAGUK p55 subfamily member 7 was associated with cancer-related fibroblasts and CD8+ T cells. Gene enrichment analysis indicated that MAGUK p55 subfamily member 7 influences cancer through the Rap1 signaling pathway. This paper elucidates the biological significance of MAGUK p55 subfamily member 7 in human pan-cancer prognosis and immune response.

In 2022, we monitored the Western Snowy Plover (WSP) population at Coal Oil Point Reserve as in previous years. The number of breeding adults was 52, higher than the average of 37 for our site. The wintering population size was 183, also above the average of 167. Skunk predation was the primary cause of nest failure. In response to the high levels of predation by skunks and the failure to trap them, all nests present on or laid after April 29th and before May 31st were collected, incubated until near the hatching date, and then returned to the parents. The real eggs were replaced with wooden eggs so that the parents would continue incubating. 35 nests (34%) of nests this season were replaced using this method. The hatching and fledging success rates in this report reflect those that hatched and fledged naturally and exclude nests that had eggs replaced. Hatching rate (28%) was lower than average (53%) and the fledging rate (74%) was higher than average (62%). The number of fledged chicks per male (1.0) met our site's recovery goal of 1.0 fledged chicks per male. 92% of nests (94) were initiated on the beach, and 8% (8) were initiated on the mudflats of the slough (delta).

Introduction There is an ongoing scientific discussion, that anti-cancer effects induced by radiofrequency (RF)-hyperthermia might not be solely attributable to subsequent temperature elevations at the tumor site but also to non-temperature-induced effects. The exact molecular mechanisms behind said potential non-thermal RF effects remain largely elusive, however, limiting their therapeutical targetability.Objective Therefore, we aim to provide an overview of the current literature on potential non-temperature-induced molecular effects within cancer cells in response to RF-electromagnetic fields (RF-EMF).Material and Methods This literature review was conducted following the PRISMA guidelines. For this purpose, a MeSH-term-defined literature search on MEDLINE (PubMed) and Scopus (Elsevier) was conducted on March 23rd, 2024. Essential criteria herein included the continuous wave RF-EMF nature (3 kHz − 300 GHz) of the source, the securing of temperature-controlled circumstances within the trials, and the preclinical nature of the trials.Results Analysis of the data processed in this review suggests that RF-EMF radiation of various frequencies seems to be able to induce significant non-temperature-induced anti-cancer effects. These effects span from mitotic arrest and growth inhibition to cancer cell death in the form of autophagy and apoptosis and appear to be mostly exclusive to cancer cells. Several cellular mechanisms were identified through which RF-EMF radiation potentially imposes its anti-cancer effects. Among those, by reviewing the included publications, we identified RF-EMF-induced ion channel activation, altered gene expression, altered membrane potentials, membrane oscillations, and blebbing, as well as changes in cytoskeletal structure and cell morphology.Conclusion The existent literature points toward a yet untapped therapeutic potential of RF-EMF treatment, which might aid in damaging cancer cells through bio-electrical and electro-mechanical molecular mechanisms while minimizing adverse effects on healthy tissue cells. Further research is imperative to definitively confirm non-thermal EMF effects as well as to determine optimal cancer-type-specific RF-EMF frequencies, field intensities, and exposure intervals.

Background: Studies attempting to distinguish suicide attempters from ideators have found that impulsivity is consistently associated with attempts across the spectrum of suicidal behavior from self-harm to lethal suicidal behavior. Impulsivity is readily assessed using complementary clinical and laboratory measures, making it a viable target for pharmacological strategies to prevent suicide risk. Lithium reduces suicidal behavior across diagnoses, and has been implicated in the reduction of impulsivity triggered by stress mediated phosphatidylinositol turnover. We used a placebo controlled cross-over design to study the effects of repeated lithium dosing on risk factors predisposing to suicidal behavior. Methods: 15 patients with a recent (past year) medically severe suicide attempt (MSSA) (37.5% male, 40.13 ± 13.66 years) received lithium carbonate and matching pill placebo separately in a randomized double-blind crossover design administered six weeks apart. To test the effect of lithium on measures of impulsivity and arousal, participants completed the Immediate Memory Task (IMT), Internal State Scale (ISS), and the Time Perception Task (TPT). We conducted separate analyses for each variable using repeated measures analysis of covariance. Results: Lithium dosing was associated with increased IMT response latency (p = .017, pη2 = 0.23), and decision bias (p = .048, pη2 = 0.21). Lithium did not significantly alter time perception or activation. Conclusions: Our results suggest that lithium may reduce risk in MSSA survivors by increasing the response latency and increasing conservative response bias during decision-making. Future studies should conduct long-term follow-ups with adjunct behavioral therapy with lithium on factors contributing to suicidal behavior.

The integration of digital interventions in health rehabilitation offers promising opportunities to improve patient outcomes. However, empirical studies comparing the effectiveness of digital and traditional rehabilitation interventions remain scarce. This study was designed to evaluate the impact of a digital aftercare program, compared to traditional aftercare and a control group, on both psychological and physical health outcomes in individuals undergoing orthopedic rehabilitation. Additionally, the study also aimed to examine the moderating effects of age and gender. The study employed a partially controlled trial design, engaging a cohort of 805 orthopedic patients, divided into: digIRENA (n = 323, digital aftercare), IRENA (n = 252, traditional aftercare), and a control group (n = 230, without organized aftercare). Measurements took place at four different time points: baseline (start of the rehabilitation program), T1 (13 weeks after the start of rehabilitation, marking the midpoint of aftercare), T2 (26 weeks, marking the end of aftercare), and T3 (43 weeks, to assess the sustainability of aftercare effects). The SF-12 Health Survey was the primary data collection instrument for measuring trends in physical and mental health outcomes over these intervals using repeated measures ANOVA. The results show that rehabilitants in the digIRENA group participated for a longer period of time than rehabilitants in the IRENA group, while the two groups did not differ in terms of motivation at T0 and organized physical activity outside of aftercare at T3. A significant improvement in physical health outcomes was observed in all groups across time, with digIRENA participants showing the greatest improvement. For mental health, all groups showed initial improvements, with the digIRENA group showing the most pronounced increase at T2. Overall, there was a decline in the effects achieved 4 months after the end of aftercare. When age and gender were included as covariates, the time effect for mental health disappeared, showing a significant time * gender interaction due to significantly lower baseline scores of women compared to men. The results of the study show that digital interventions, in particular the digIRENA program, contribute to improving health rehabilitation outcomes. The digIRENA program and similar digital health interventions may offer potential for improving health rehabilitation aftercare.

Converging evidence of high stress levels in the nursing profession as well as their detrimental effects on the execution of nursing actions, quality indicators of care, and self-reported job satisfaction justify the need for test environments that assess stress coping competences in dealing with domain-specific stress factors. Reliable and valid information on the test takers' stress coping competence can help to identify individual deficits and supportive needs and thus, to design training measures that may contribute to job retention and a skilled workforce. This article describes the development and validation of a digital assessment that ensures authenticity by means of video-based situational judgement tests. Analyses of the performance data were conducted in four steps: (1) the scaling of the data with a partial credit model in order to identify items that are subject to measurement error, (2) differential-item-function analyses for different specializations in nursing education, (3) dimensionality tests, and (4) correlations between test performance and perceived psychological work stress in order to gauge criterion validity. The total sample consisted of n = 300 German nursing apprentices. The results show that the developed test instrument can be used for a reliable and valid measurement of coping skills of (prospective) nurses, covering two essential dimensions. Limitations of the current study and related objectives of future research are discussed together with questions of practical applicability.

Background and aimRehabilitation programs have been shown to have a positive impact on patients' health and work ability. However, the durability of these effects and the extent to which patients alter their health behaviors remain underexplored. This study is divided into two parts; the first assesses the effectivity of rehabilitation programs for orthopedic patients and the durability of effects. The second part examines psychological determinants of aftercare health behaviors.Subject and methodsStudy Part 1 employs a longitudinal study design with up to nine measurement occasions encompassing a three-year follow-up period. Treatment is provided as per orthopedic indications through rehabilitation centers. Measures include subjective health, work ability, body weight, and physical activity behavior. Study Part 2 incorporates a mixed-methods design, involving both quantitative and qualitative assessments. The quantitative component aims to recruit a subsample from Study Part 1 to assess psychological determinants of aftercare health behaviors over 12 to 24 weeks using Ambulatory Assessment. The qualitative component aims to explore the reasons for maintenance and discontinuation of health behaviors and involves a reflexive thematic analysis of interviews with at least 16 individuals, analyzing the differences between those who adopt and those who discontinue their aftercare health behavior.DiscussionThis comprehensive research project may offer insights into the long-term effectivity of rehabilitation programs. Furthermore, it may foster a more profound understanding of the successful incorporation of health-promoting aftercare behaviors, such as physical activity, into everyday life. Therefore, this study may contribute significantly to the evolving field of patient-centered rehabilitation.Trial registrationThe trial has been registered at the German Register of Clinical Studies (DRKS) with the registration number: DRKS00032257

Klebsiella pneumoniae is a Gram-negative bacterium within the Enterobacteriaceae family that can cause multiple systemic infections, such as respiratory, blood, liver abscesses and urinary systems. Antibiotic resistance is a global health threat and K. pneumoniae warrants special attention due to its resistance to most modern day antibiotics. Biofilm formation is a critical obstruction that enhances the antibiotic resistance of K. pneumoniae. However, knowledge on the molecular mechanisms of biofilm formation and its relation with antibiotic resistance in K. pneumoniae is limited. Understanding the molecular mechanisms of biofilm formation and its correlation with antibiotic resistance is crucial for providing insight for the design of new drugs to control and treat biofilm-related infections. In this review, we summarize recent advances in genes contributing to the biofilm formation of K. pneumoniae, new progress on the relationship between biofilm formation and antibiotic resistance, and new therapeutic strategies targeting biofilms. Finally, we discuss future research directions that target biofilm formation and antibiotic resistance of this priority pathogen.

In recent years, considerable achievements have been made in pediatric oncology with the innovation and development of antitumor drugs. However, compared to adults, children as a special group have not yet matured fully in terms of liver and kidney function. Moreover, pediatric patients are prone to more adverse drug reactions (ADRs) from the accumulation of antineoplastic drugs due to their smaller body size and larger body surface area. Chemotherapy-related ADRs have become a non-negligible factor that affects cancer remission. To date, studies on ADRs in pediatric cancer patients have emerged internationally, but few systematic summaries are available. Here, we reviewed the various systemic ADRs associated with antitumor drugs in children and adolescent patients, as well as the advances in strategies to cope with ADRs, which consisted of neurotoxicity, hematological toxicity, cardiotoxicity, ADRs of the respiratory system and gastrointestinal system and urinary system, ADRs of the skin and its adnexa, allergic reactions, and other ADRs. For clinicians and researchers, understanding the causes, symptoms, and coping strategies for ADRs caused by anticancer treatments will undoubtedly benefit more children.

Akkermansia muciniphila is a gram-negative bacterium that colonizes the human gut, making up 3–5% of the human microbiome. A. muciniphila is a promising next-generation probiotic with clinical application prospects. Emerging studies have reported various beneficial effects of A. muciniphila including anti-cancer, delaying aging, reducing inflammation, improving immune function, regulating nervous system function, whereas knowledge on its roles and mechanism in infectious disease is currently unclear. In this review, we summarized the basic characteristics, genome and phenotype diversity, the influence of A. muciniphila and its derived components on infectious diseases, such as sepsis, virus infection, enteric infection, periodontitis and foodborne pathogen induced infections. We also provided updates on mechanisms how A. muciniphila protects intestinal barrier integrity and modulate host immune response. In summary, we believe that A. muciniphila is a promising therapeutic probiotic that may be applied for the treatment of a variety of infectious diseases.

Abstract Background This quasi-experimental study aimed to compare the effectiveness of a digital prevention intervention on work ability, physical health, and mental health with a conventional prevention program for employees with initial impairments. The study recruited 245 participants, of whom 173 completed the study, 98 (65 female, 66.3%) in the intervention group and 75 (55 female, 73.3%) in the control group. Both groups received prevention programs, with the intervention group using the Caspar digital platform and the control group using the conventional BETSI/RV Fit program. There were three measurement points in the study: T0 before the intervention, T1 in the middle of the intervention, and T2 at the end of the intervention. Participants’ health was assessed using the SF-12 health status questionnaire, while their work ability was measured using the short version of the Work Ability Index. Results Repeated-measures analyses of variance indicated that both prevention programs were effective in improving work ability and mental health, while physical health did not show any significant improvement. Additionally, the results of the study suggest that younger individuals benefited more from the digital prevention intervention, while older individuals benefited more from the conventional prevention program. Conclusion The study emphasizes the need for further research and improvements in both research and practice. Future studies should include larger sample sizes, randomized controlled trials, and follow-up assessments to enhance understanding of the effectiveness and the durability of effects of prevention programs.

Abstract High-risk neuroblastoma (HR-NB) has a significantly lower survival rate compared to low- and intermediate-risk NB (LIR-NB) due to the lack of risk classification diagnostic models and effective therapeutic targets. The present study aims to characterize the differences between neuroblastomas with different risks through transcriptomic and metabolomic, and establish an early diagnostic model for risk classification of neuroblastoma.Plasma samples from 58 HR-NB and 38 LIR-NB patients were used for metabolomics analysis. Meanwhile, NB tissue samples from 32 HR-NB and 23 LIR-NB patients were used for transcriptomics analysis. In particular, integrative metabolomics and transcriptomic analysis was performed between HR-NB and LIR-NB. A total of 44 metabolites (P 1.5) were altered, including 12 that increased and 32 that decreased in HR-NB. A total of 1,408 mRNAs (P 1) showed significantly altered in HR-NB, of which 1,116 were upregulated and 292 were downregulated. Joint analysis of both omic data identified 4 aberrant pathways (P

Abstract Beyond climate change, the planet faces several other environmental challenges that are at least as threatening, such as the loss of biodiversity. In each case, the problems are driven by similar factors, such as fossil fuels and intensive livestock farming. This paper presents a legal analysis concerning the binding nature of the Convention on Biological Diversity’s (CBD) overarching objective to halt biodiversity loss, within the framework of international environmental and human rights law. Using the established legal techniques encompassing grammatical, systematic, teleological, and historical interpretations, the article demonstrates that the CBD’s objective to halt biodiversity loss is indeed legally binding and justiciable. This conclusion is directly drawn from interpreting Article 1 CBD. Furthermore, a comparable obligation emerges indirectly from international climate law. The imperative to curtail biodiversity loss also finds grounding in human rights law, albeit necessitating a re-evaluation of certain aspects of freedom, similar to what has been explored in the context of climate protection. Moreover, the article underscores that various other biodiversity-related regulations within international law, including those laid out in the CBD, the Aichi Targets, and the Kunming–Montreal Global Biodiversity Framework, also carry partial legal significance. Nonetheless, it is crucial to note that these regulations, including the Kunming–Montreal Framework, do not modify the obligation mandate to halt biodiversity loss, which was established at the latest when the CBD entered into force in 1993. Because this obligation has been violated since then, states could potentially be subject to legal action before international or domestic courts for their actions or inactions contributing to global biodiversity loss.

The Coal Oil Point Reserve Annual Newsletter highlights the conservation, restoration, and research projects at the reserve in 2021.

Abstract Background Combined chemoradiation offers a promising therapeutic strategy for dogs with glioma. The alkylating agents temozolomide (TMZ) and lomustine (CCNU) penetrate the blood‐brain barrier, and doses for dogs are established. Whether such combinations are clinically advantageous remains to be explored together with tumour‐specific markers. Objective To investigate if triple combination of lomustine, temozolomide and irradiation reduces canine glioma cell survival in vitro. Methods We evaluated the sensitising effect of CCNU alone and in combination with TMZ‐irradiation in canine glioma J3T‐BG cells and long‐term drug‐exposed subclones by using clonogenic survival and proliferation assays. Bisulphite‐SEQ and Western Blot were used to investigate molecular alterations. Results TMZ (200 μM) or CCNU alone (5 μM) reduced the irradiated survival fraction (4 Gy) from 60% to 38% (p = 0.0074) and 26% (p = 0.0002), respectively. The double‐drug combination reduced the irradiated survival fraction (4 Gy) more potently to 12% (p < 0.0001). After long‐term drug exposure, both subclones show higher IC50 values against CCNU and TMZ. For CCNU‐resistant cells, both, single‐drug CCNU (p = 0.0006) and TMZ (p = 0.0326) treatment combined with irradiation (4 Gy) remained effective. The double‐drug‐irradiation combination reduced the cell survival by 86% (p < 0.0001), compared to 92% in the parental (nonresistant) cell line. For TMZ‐resistant cells, only the double‐drug combination with irradiation (4 Gy) reduced the cell survival by 88% (p = 0.0057) while single‐drug treatment lost efficacy. Chemoresistant cell lines demonstrated higher P‐gp expression while MGMT‐methylation profile analysis showed a general high methylation level in the parental and long‐term treated cell lines. Conclusions Our findings indicate that combining CCNU with TMZ‐irradiation significantly reduces canine glioma cell survival. Such a combination could overcome current challenges of therapeutic resistance to improve overall patient survival.

Abstract Converging evidence of high stress levels in the nursing profession as well as their detrimental effects on the execution of nursing actions, quality indicators of care, and self-reported job satisfaction justify the need for test environments that assess stress coping competences in dealing with domain-specific stress factors. Reliable and valid information on the test takers’ stress coping competence can help to identify individual deficits and supportive needs and thus, to design training measures that may contribute to job retention and a skilled workforce. This article describes the development and validation of a digital assessment that ensures authenticity by means of video-based situational judgement tests. Analyses of the performance data were conducted in four steps: (1) the scaling of the data with a partial credit model in order to identify items that are subject to measurement error, (2) differential-item-function analyses for different specializations in nursing education, (3) dimensionality tests, and (4) correlations between test performance and perceived psychological work stress in order to gauge criterion validity. The total sample consisted of n = 300 German nursing apprentices. The results show that the developed test instrument can be used for a reliable and valid measurement of coping skills of (prospective) nurses, covering two essential dimensions. Limitations of the current study and related objectives of future research are discussed together with questions of practical applicability.

Background The optimal reperfusion technique in patients with isolated posterior cerebral artery (PCA) occlusion is uncertain. We compared clinical and technical outcomes with first‐line stent retriever (SR), contact aspiration (CA), or combined techniques in patients with isolated PCA occlusion. Methods This international case–control study was conducted at 30 sites in Europe and North America and included consecutive patients with isolated PCA occlusion presenting within 24 hours of time last seen well from January 2015 to August 2022. The primary outcome was the first‐pass effect (FPE), defined as expanded Treatment in Cerebral Infarction (TICI) 2c/3 on the first pass. Patients treated with SR, CA, or combined technique were compared with multivariable logistic regression. Results There were 326 patients who met inclusion criteria, 56.1% male, median age 75 (interquartile range 65–82) years, and median National Institutes of Health Stroke Scale score 8 (5–12). Occlusion segments were PCA‐P1 (53.1%), P2 (40.5%), and other (6.4%). Intravenous thrombolysis was administered in 39.6%. First‐line technique was SR, CA, and combined technique in 43 (13.2%), 106 (32.5%), and 177 (54.3%) patients, respectively; FPE was achieved in 62.8%, 42.5%, and 39.6%, respectively. FPE was lower in patients treated with first‐line CA or combined technique compared with SR (CA versus SR: adjusted odds ratio 0.45 [0.19–1.06]; P=0.07; combined versus SR: adjusted odds ratio 0.35 [0.016–0.80]; P=0.01). There were lower odds of functional independence (modified Rankin scale score 0–2) in the first‐line CA versus SR alone group (adjusted odds ratio 0.52 [0.28–0.95]; P=0.04). FPE was associated with higher rates of favorable outcomes (modified Rankin scale score 0–2: 58% versus 43.4%; P=0.01; modified Rankin scale score 0–1: 36.6% versus 25.8%; P=0.05). Overall, symptomatic intracranial hemorrhage was present in 5.6% (18/326) and mortality in 10.9% (35/326) without difference between first‐line technique. Conclusion In patients with isolated PCA occlusion, SR was associated with a higher rate of FPE compared with CA or combined techniques with no difference in final successful reperfusion. Functional independence at 90 days was more likely with first‐line SR compared with CA. FPE was associated with better 90‐day clinical outcomes.

Introduction The optimal reperfusion technique in patients with isolated posterior cerebral artery (PCA) occlusion is uncertain. Previous studies in LVO and MeVO have demonstrated a correlation between good clinical outcomes and the first pass effect (FPE, eTICI 2c/3 on the first pass) but no differences in FPE rates or clinical outcomes between first‐line endovascular therapy techniques.1‐6 We compared clinical and technical outcomes with first‐line stent‐retriever (SR), contact aspiration (CA), or combined techniques in patients with isolated PCA occlusion. Methods This international cohort study was conducted at 30 sites in Europe and North America and included consecutive patients with isolated PCA occlusion and pre‐stroke modified Rankin Scale (mRS) 0‐3, presenting within 24 hours of time last seen well from January 2015 to August 2022.7 The primary outcome was the first‐pass effect (FPE), defined as eTICI 2c/3 on the first pass. Secondary outcomes included final successful reperfusion (eTICI 2b‐3), 90‐day excellent outcome (mRS 0 to 1), 90‐day functional independence (mRS 0 to 2), sICH, and 90‐day mortality. Patients treated with SR, CA, or combined technique were compared with multivariable logistic regression. This study was registered under NCT05291637. Results There were 326 patients who met inclusion criteria, consisting of 56.1% male, median age 75 (IQR 65‐82) years and median NIHSS 8 (5‐12). Occlusion segments were PCA P1 (53.1%), P2 (40.5%), and other (6.4%). Intravenous thrombolysis was administered in 39.6%. First‐line technique was SR, CA, and combined technique in 43 (13.2%), 106 (32.5%), and 177 (54.3%) patients, respectively; FPE was achieved in 62.8%, 42.5%, and 39.6%, respectively. Compared to SR, FPE was lower in patients treated with first‐line combined technique and similar in patients treated with first‐line CA (combined vs. SR: aOR 0.35 [0.016‐0.80], p=0.01; CA vs. SR: aOR 0.45 [0.19‐1.06], p=0.07). Final successful reperfusion (eTICI 2b‐3) was present in 81% of cases with no differences between treatment groups. Excellent outcome (mRS 0‐1) occurred in 30.7% of patients and functional independence (mRS 0‐2) occurred in 50.0% of patients. There were lower odds of functional independence in the first‐line CA versus SR alone group (aOR 0.52 [0.28‐0.95], p=0.04). FPE was associated with higher rates of favorable outcomes (mRS 0‐2: 58% vs. 43.4%, p=0.01; mRS 0‐1: 36.6% vs. 25.8%, p=0.05). sICH was observed in 5.6% (18/326) and mortality in 10.9% (35/326) with no differences between first‐line technique. Conclusion In patients with isolated PCA occlusion undergoing EVT, first line SR was associated with a higher rate of FPE compared to CA or combined techniques with no difference in final successful reperfusion. Functional independence at 90‐days was more likely with first‐line SR compared to CA in adjusted analyses. FPE was associated with higher rates of 90‐day excellent outcomes and functional independence. No difference in sICH or mortality was noted across the three techniques. As the endovascular field evolves to treat patients with distal vessel occlusion and milder severity of stroke, optimizing the efficacy and safety of the procedure is essential.8

Background For acute proximal intracranial artery occlusions, contact aspiration may be more effective than stent‐retriever for first‐line reperfusion therapy. Due to the lack of data regarding medium vessel occlusion thrombectomy, we evaluated outcomes according to first‐line technique in a large, multicenter registry. Methods Imaging, procedural, and clinical outcomes of patients with acute proximal medium vessel occlusions (M2, A1, or P1) or distal medium vessel occlusions (M3, A2, P2, or further) treated at 37 sites in 10 countries were analyzed according to first‐line endovascular technique (stent‐retriever versus aspiration). Multivariable logistic regression and propensity‐score matching were used to estimate the odds of the primary outcome, expanded Thrombolysis in Cerebral Infarction score of 2b–3 (“successful recanalization”), as well as secondary outcomes (first‐pass effect, expanded Thrombolysis in Cerebral Infarction 2c‐3, intracerebral hemorrhage, and 90‐day modified Rankin scale, 90‐day mortality) between treatment groups. Results Of the 440 included patients (44.5% stent‐retriever versus 55.5% aspiration), those treated with stent‐retriever had lower baseline Alberta Stroke Program Early Computed Tomography Scale scores (median 8 versus 9; P

The Indochina biomass burning (BB) season in springtime has a substantial environmental impact on the surrounding areas in Asia. In this study, we evaluated the environmental impact of a major long-range BB transport event on 19 March 2018 (a flight of the High Altitude and Long Range Research Aircraft (HALO; https://www.halo-spp.de, last access: 14 February 2023) research aircraft, flight F0319) preceded by a minor event on 17 March 2018 (flight F0317). Aircraft data obtained during the campaign in Asia of the Effect of Megacities on the transport and transformation of pollutants on the Regional to Global scales (EMeRGe) were available between 12 March and 7 April 2018. In F0319, results of 1 min mean carbon monoxide (CO), ozone (O3), acetone (ACE), acetonitrile (ACN), organic aerosol (OA), and black carbon aerosol (BC) concentrations were up to 312.0, 79.0, 3.0, and 0.6 ppb and 6.4 and 2.5 µg m−3, respectively, during the flight, which passed through the BB plume transport layer (BPTL) between the elevation of 2000–4000 m over the East China Sea (ECS). During F0319, the CO, O3, ACE, ACN, OA, and BC maximum of the 1 min average concentrations were higher in the BPTL by 109.0, 8.0, 1.0, and 0.3 ppb and 3.0 and 1.3 µg m−3 compared to flight F0317, respectively. Sulfate aerosol, rather than OA, showed the highest concentration at low altitudes ( m) in both flights F0317 and F0319 resulting from the continental outflow in the ECS. The transport of BB aerosols from Indochina and its impacts on the downstream area were evaluated using a Weather Research Forecasting with Chemistry (WRF-Chem) model. The modeling results tended to overestimate the concentration of the species, with examples being CO (64 ppb), OA (0.3 µg m−3), BC (0.2 µg m−3), and O3 (12.5 ppb) in the BPTL. Over the ECS, the simulated BB contribution demonstrated an increasing trend from the lowest values on 17 March 2018 to the highest values on 18 and 19 March 2018 for CO, fine particulate matter (PM2.5), OA, BC, hydroxyl radicals (OH), nitrogen oxides (NOx), total reactive nitrogen (NOy), and O3; by contrast, the variation of J(O1D) decreased as the BB plume's contribution increased over the ECS. In the lower boundary layer ( m), the BB plume's contribution to most species in the remote downstream areas was %. However, at the BPTL, the contribution of the long-range transported BB plume was as high as 30 %–80 % for most of the species (NOy, NOx, PM2.5, BC, OH, O3, and CO) over southern China (SC), Taiwan, and the ECS. BB aerosols were identified as a potential source of cloud condensation nuclei, and the simulation results indicated that the transported BB plume had an effect on cloud water formation over SC and the ECS on 19 March 2018. The combination of BB aerosol enhancement with cloud water resulted in a reduction of incoming shortwave radiation at the surface in SC and the ECS by 5 %–7 % and 2 %–4 %, respectively, which potentially has significant regional climate implications.

The identification of effects of vocational education and training conditions on competence development in nursing education requires longitudinal studies. An important precondition is the availability of a test of nursing competence which is economical in use, measures a homogeneous construct throughout years of nursing education and across nursing specializations, and can detect increases in the required competence, hence allowing for sensitive testing. This article describes a cross-sectional study that aimed to optimize a computer-based test measuring nursing competence in care for the elderly--the TEMA test--through the selection of items on the basis of measurement error, differential item functioning, and item difficulty. Evidence of the test sensitivity of the optimized TEMA-L instrument is presented for the second and third year of nursing education. The total sample consisted of n = 133 German nursing students from clinical and geriatric nursing. The resulting instrument includes two test booklets consisting of 36 (WLE = 0.72) and 35 items (WLE = 0.70) respectively for the second and third year of training. The cross-sectional data indicate that the test likely has good properties for sensitive testing of nursing competence in a future longitudinal study. Hence, it might be used to study factors contributing to increases in nursing competence in German VET and serve as an example for similar studies in other countries. Limitations of the current study and related subjects of future research are discussed.

Background and aimsOctogenarians are underrepresented in recently published studies that showed the benefit of endovascular stroke treatment (EST) for patients with acute basilar artery occlusion (BAO). We aimed to compare the clinical outcome of octogenarians with BAO and EST compared to younger patients (YPs) and identify independent outcome predictors.MethodsThis is a retrospective, single-center analysis of patients treated for BAO with EST from January 2013 until June 2021 in a tertiary stroke center. Octogenarians (80–89 years) were compared to YPs. A study endpoint was a favorable clinical outcome as per the modified Rankin Scale (mRS 0–3), 90 days after stroke onset. The study groups were compared using univariate analysis, and a multivariable logistic regression analysis was performed to define independent predictors for favorable and unfavorable (mRS 5–6) clinical outcomes.ResultsIn this study cohort, 74/191 (38.7%) octogenarians had a higher pre-stroke mRS [median, interquartile range (IQR): 2, 1–3 octogenarians vs. 0, 0–1 YP, p < 0.001] and a comparable National Institutes of Health Stroke Scale (NIHSS) before EST (median, IQR: 21, 10–38 vs. 20, 8–35 in YP, p = 0.487). They showed a comparable rate of favorable outcome (mRS 0–3, 90 days, 23.0 vs. 25.6% in YP, p = 0.725), but were less often functionally independent (mRS 0–2: 10.8% in octogenarians vs. 23.0% in YP, p = 0.049). The rate of unfavorable clinical outcome was comparable (mRS 5–6, n = 40, 54.1% in octogenarians vs. n = 64, 54.7% in YP, p = 0.831). A baseline NIHSS was an independent predictor for clinical outcome in YPs [e.g., for unfavorable clinical outcome: odds ratio (OR) 1.061, confidence interval (CI) 1.027–1.098, p = 0.005] and for favorable clinical outcome in octogenarians. Pre-stroke mRS predicted favorable outcomes in octogenarians (OR 0.54, CI 0.30–0.90, p = 0.0291), while age predicted unfavorable outcomes in YPs (OR 1.045, CI 1.011–1.086, p = 0.0137).ConclusionOctogenarians with acute BAO eligible for EST are as likely to achieve a favorable outcome as YPs, and the rate of death or severe disability is comparable. The admission NIHSS is an independent predictor for favorable and unfavorable outcomes in YP and for favorable outcomes in octogenarians. In this study cohort, pre-stroke mRS predicted favorable outcomes in octogenarians while age predicted an unfavorable outcome in YPs.

We report on airborne limb and nadir measurements of vertical profiles and total vertical column densities (VCDs) of glyoxal (C2H2O2) in the troposphere, which were performed aboard the German research aircraft HALO (High Altitude and LOng Range) in different regions and seasons around the globe between 2014 and 2019. The airborne nadir and integrated limb profiles agree excellently among each other. Our airborne observations are further compared to collocated glyoxal measurements of the TROPOspheric Monitoring Instrument (TROPOMI), with good agreement between both data sets for glyoxal observations in (1) pristine terrestrial, (2) pristine marine, (3) mixed polluted, and (4) biomass-burning-affected air masses with high glyoxal concentrations. Exceptions to the overall good agreement are observations of (1) faint and aged biomass burning plumes over the oceans and (2) of low-lying biomass burning or anthropogenic plumes in the terrestrial or marine boundary layer, both of which contain elevated glyoxal that is mostly not captured by TROPOMI. These differences in airborne and satellite-detected glyoxal are most likely caused by the overall small contribution of plumes of a limited extent to the total glyoxal absorption in the atmosphere and the difficulty in remotely detecting weak absorbers located close to low reflective surfaces (e.g. the ocean in the visible wavelength range) or within dense aerosol layers. Observations of glyoxal in aged biomass burning plumes (e.g. observed over the tropical Atlantic off the coast of West Africa in summer 2018, off the coast of Brazil by the end of the dry season 2019, and the East China Sea in spring 2018) could be traced back to related wildfires, such as a plume crossing over the Drake Passage that originated from the Australian bushfires in late 2019. Our observations of glyoxal in such aged biomass burning plumes confirm recent findings of enhanced glyoxal and presumably secondary organic aerosol (SOA) formation in aged wildfire plumes from yet-to-be-identified, longer-lived organic precursor molecules (e.g. aromatics, acetylene, or aliphatic compounds) co-emitted in the fires. Furthermore, elevated glyoxal (median 44 ppt – parts per trillion), as compared to other marine regions (median 10–19 ppt), is observed in the boundary layer over the tropical oceans, which is well in agreement with previous reports. The airborne data sets are further compared to glyoxal simulations performed with the global atmosphere chemistry model EMAC (ECHAM/MESSy Atmospheric Chemistry). When using an EMAC set up that resembles recent EMAC studies focusing on complex chemistry, reasonable agreement is found for pristine air masses (e.g. the unperturbed free and upper troposphere), but a notable glyoxal overestimation of the model exists for regions with high emissions of glyoxal and glyoxal-producing volatile organic compounds (VOCs) from the biosphere (e.g. the Amazon). In all other investigated regions, the model underpredicts glyoxal to varying degrees, in particular when probing mixed emissions from anthropogenic activities (e.g. over continental Europe, the Mediterranean, and East China Sea) and potentially from the sea (e.g. the tropical oceans). Also, the model tends to largely underpredict glyoxal in city plumes and aged biomass burning plumes. The potential causes for these differences are likely to be multifaceted, but they all point to missing glyoxal sources from the degradation of the mixture of potentially longer-chained organic compounds emitted from anthropogenic activities, biomass burning, and from the organic microlayer of the sea surface.

Abstract Purpose The treatment of vasospasms during endovascular stroke treatment (EST) with intra-arterial nimodipine (NM) is routinely performed. However, the efficacy of resolving iatrogenic vasospasms during the angiographic intervention and the infarct development in follow-up imaging after EST has not been studied yet. Methods Retrospective single-center analysis of patients receiving EST for anterior circulation vessel occlusion between 01/2015 and 12/2021. The primary endpoint was ASPECTS in follow-up imaging. Secondary endpoints were the clinical outcome (combined endpoint NIHSS 24 h after EST and difference between modified Rankin Scale (mRS) before stroke and at discharge (delta mRS)) and intracranial hemorrhage (ICH) in follow-up imaging. Patients with vasospasms receiving NM (NM+) or not (NM-) were compared in univariate analysis. Results Vasospasms occurred in 79/1283 patients (6.2%), who consecutively received intra-arterial NM during EST. The targeted vasospasm angiographically resolved in 84% (66/79) under NM therapy. ASPECTS was lower in follow-up imaging after vasospasms and NM-treatment (NM – 7 (6–9), NM + 6 (4.5-8), p = 0.013) and the clinical outcome was worse (NIHSS 24 h after EST was higher in patients treated with NM (median, IQR; NM+: 14, 5–21 vs. NM-: 9, 3–18; p = 0.004), delta-mRS was higher in the NM + group (median, IQR; NM+: 3, 1–4 vs. NM-: 2, 1–2; p = 0.011)). Any ICH (NM+: 27/79, 34.2% vs. NM-: 356/1204, 29.6%; p = 0.386) and symptomatic ICH (NM+: 2/79, 2.5% vs. NM-: 21/1204, 1.7%; p = 0.609) was equally distributed between groups. Conclusion Intra-arterial nimodipine during EST resolves iatrogenic vasospasms efficiently during EST without increasing intracranial hemorrhage rates. However, patients with vasospasms and NM treatment show higher infarct growth resulting in lower ASPECTS in follow-up imaging.

Abstract Background The purpose of this study was to evaluate the safety and efficacy of vancomycin-loaded calcium sulfate beads and negative-pressure wound therapy (NPWT) in treating children with acute hematogenous osteomyelitis (AHOM). Methods A retrospective cohort study was conducted from January 2017 to January 2020 examining children (n = 60) with AHOM who were treated with surgical debridement followed by vancomycin-loaded calcium sulfate beads and NPWT (n = 32) and compared to treatment by conventional surgical debridement (n = 28) followed by NPWT. Conventional surgical treatment consisted of fenestration of necrotic infected bone, debridement of surrounding soft tissue, and washing of the medullary canal before the application of NPWT. In the vancomycin group, the antibiotic-loaded beads were implanted after washing the medullary canal and before the application of NPWT. Epidemiological factors, complications during the procedure, outcomes at last follow-up (30.0 ± 11.7 months, range 13–58 months), and laboratory parameters were documented and compared between the two groups. Results Good outcomes were achieved at last follow-up in 71.4% of the conventional treatment group and 75% of the vancomycin group. In the vancomycin group, it took a mean of 4.8 ± 2.5 days for CRP levels to decrease to 50% of initial inflammatory levels compared to 13 ± 9.6 days for the conventional treatment group (p = 0.001, t-test). The conventional group also had seven patients who underwent four or more surgeries whereas no patients in the vancomycin group underwent more than three surgeries (p = 0.013, chi-square test). Conclusion Localized vancomycin delivery with NPWT effective for treating cases of AHOM that required. No perioperative adverse reactions or complications occurred from this treatment method. Based on the shortened recovery period of CRP levels, prolonged administration of post-operational parenteral antibiotics can possibly be reduced with this treatment method.

Existing curricula for entrepreneurship education do not necessarily represent the best way of teaching. How could entrepreneurship curricula be improved? To answer this question, we aim to identify and rank desirable teaching objectives, teaching contents, teaching methods, and assessment methods for higher entrepreneurship education. To this end, we employ an international real-time Delphi study with an expert panel consisting of entrepreneurship education instructors and researchers. The study reveals 17 favorable objectives, 17 items of content, 25 teaching methods, and 15 assessment methods, which are ranked according to their desirability and the group consensus. We contribute to entrepreneurship curriculum research by adding a normative perspective.

Entrepreneurship education research has a strong “output” focus on impact studies but pays much less attention to the “inside” or process perspective of the way entrepreneurship education occurs. In particular, the scattered previous entrepreneurship curriculum research has not managed to provide a current and comprehensive overview of the curricular elements that constitute entrepreneurship education. To overcome this shortcoming, we aim to identify the teaching objectives, teaching contents, teaching methods, and assessment methods discussed in entrepreneurship curriculum research. To this end, we conducted a systematic literature review on the four entrepreneurship curriculum dimensions and collected all mentioned curriculum items. We used a two-stage coding procedure to find the genuinely entrepreneurship-specific items. Among numerous items (also from business management and other subjects), we found 26 objectives, 34 contents, 11 teaching methods, and 7 assessment methods that were entrepreneurship-specific. Most of these items were addressed by only a few scholarly papers.