Intrahepatic neutrophil accumulation and extracellular trap formation are associated with posthepatectomy liver failure.

BACKGROUND: Posthepatectomy liver failure (PHLF) represents a life-threatening complication with limited therapeutic options. Neutrophils play a critical and dynamic role during regeneratory processes, but their role in human liver regeneration is incompletely understood, especially as underlying liver disease, detectable in the majority of patients, critically affects hepatic regeneration. Here we explored intrahepatic neutrophil accumulation and neutrophil extracellular traps (NETs) in patients with PHLF and validated the functional relevance of NETs in a murine partial hepatectomy (PHx) model. METHODS: We investigated the influx of neutrophils, macrophages, eosinophils, and mast cells and the presence of their respective extracellular traps in liver biopsies of 35 patients undergoing hepatectomy (10 patients with PHLF) before and after the initiation of liver regeneration by fluorescence microscopy. In addition, NET formation and neutrophil activation were confirmed by plasma analysis of 99 patients (24 patients with PHLF) before and up to 5 days after surgery. Furthermore, we inhibited NETs via DNase I in a murine PHx model of mice with metabolically induced liver disease. RESULTS: We detected rapid intrahepatic neutrophil accumulation, elevated levels of myeloperoxidase release, and NET formation in regenerating human livers, with a significantly higher increase of infiltrating neutrophils and NETs in patients with PHLF. Circulating markers of neutrophil activation, including elastase, myeloperoxidase, and citrullinated histone H3, correlated with markers of liver injury. In a murine PHx model, we showed that the inhibition of NET accelerated hepatocyte proliferation and liver regeneration. CONCLUSIONS: Patients with PHLF showed accelerated intrahepatic neutrophil infiltration and NET formation, which were associated with liver damage. Further, we identified postsurgical myeloperoxidase levels as predictive markers for adverse outcomes and observed that blocking NETs in a murine PHx model accelerated tissue regeneration.

Multimethod Approach to the Low-Overpotential Region of Micro- to Macro-Scale Working Electrodes of Sub-10 nm Gold Nanoparticles in the CO2 Reduction Reaction.

The electrochemical carbon dioxide reduction reaction (CO2RR) over carbon-supported gold nanoparticles (AuNP) was investigated using a broad variety of (electro)analytical methods, including linear sweep voltammetry with a rotating disk electrode (LSV-RDE), sample-generation tip-collection mode of scanning electrochemical microscopy (SG/TC-SECM), as well as full cell tests with highly sensitive online gas chromatography (GC). In contrast to most other studies, this work focuses on the low-overpotential region (0 to -0.4 V vs RHE) where initial product formation is already detected and addresses micro- to macro-sized electrodes. The sub-10 nm AuNPs supported on three different carbon supports (CNTs and carbon blacks) were pretreated in H2/Ar to remove the stabilizer used during AuNP synthesis. LSV-RDE points toward different CO2RR mechanisms at the samples, additionally confirmed by the SG/TC-SECM and full cell tests with online GC. Besides H2 and CO, the AuNP supported on carbon nanotubes showed significant evolution of H2CO in contrast to the other two samples, which was additionally confirmed by accumulating the product during chronoamperometric RDE experiments followed by mass spectroscopic analysis. Surface analysis indicated a complete removal of residual thiolate stabilizer molecules exclusively at the AuNPs supported on carbon nanotubes, which may result in a change in the adsorption geometry or reaction mechanism at this sample. The results demonstrate the effectiveness of the combination of these multiple methods to investigate the CO2RR in the low-overpotential region.

Assessing the heterogeneity in the transmission of infectious diseases from time series of epidemiological data.

Structural features and the heterogeneity of disease transmissions play an essential role in the dynamics of epidemic spread. But these aspects can not completely be assessed from aggregate data or macroscopic indicators such as the effective reproduction number. We propose in this paper an index of effective aggregate dispersion (EffDI) that indicates the significance of infection clusters and superspreading events in the progression of outbreaks by carefully measuring the level of relative stochasticity in time series of reported case numbers using a specially crafted statistical model for reproduction. This allows to detect potential transitions from predominantly clustered spreading to a diffusive regime with diminishing significance of singular clusters, which can be a decisive turning point in the progression of outbreaks and relevant in the planning of containment measures. We evaluate EffDI for SARS-CoV-2 case data in different countries and compare the results with a quantifier for the socio-demographic heterogeneity in disease transmissions in a case study to substantiate that EffDI qualifies as a measure for the heterogeneity in transmission dynamics.

[COVID-19 and Its Potential for Disruption and Transformation in Public Health: Lessons Learned from the Perspective of Young Professionals]. / COVID-19 zwischen Disruption und Transformation der öffentlichen Gesundheit: Erste Lehren aus Perspektive des Nachwuchses.

The COVID-19 pandemic has both exposed and intensified various challenges for Public Health and the Public Health service (ÖGD) in Germany. However, it also offers a window of opportunity for effective long-term transformation of the country's Public Health system. Against this backdrop, an online survey was carried out among the members of the German Network of Young Professionals in Public Health (Nachwuchsnetzwerk Öffentliche Gesundheit (NÖG)) in October and November 2020. It sought to elicit members' experiences and views related to Public Health during the COVID-19 pandemic. The resulting preliminary "lessons learned" for the German Public Health context are presented in this article. Based on the results of the survey, recommendations were formulated which are intended to provide targeted and concrete advice for the strengthening and transformation of Public Health in Germany. The main issues that preoccupied the young professionals were the increased public and political attention to Public Health and the narrow focus on infectious disease control, the standing of Public Health in Germany and the strengths and weaknesses of Public Health structures and workforce. The recommendations are aimed at promoting long-term and holistic strengthening of Public Health, with the training of an interdisciplinary workforce of young professionals presenting a key focus.

Implementation of Transforaminal Endoscopic Lumbar Sequestrectomy in a German University Hospital Setting: A Long and Rocky Road.

OBJECTIVE: Microsurgical diskectomy/sequestrectomy is the standard procedure for the surgical treatment of lumbar disk herniations. The transforaminal endoscopic sequestrectomy technique is a minimally invasive alternative with potential advantages such as minimal blood loss and tissue damage, as well as early mobilization of the patient. We report the implementation of this technique in a German university hospital setting. METHODS: One single surgeon performed transforaminal endoscopic sequestrectomy from February 2013 to July 2016 for lumbar disk herniation in 44 patients. Demographic as well as perioperative, clinical, and radiologic data were analyzed from electronic records. Furthermore, we investigated complications, intraoperative change of the procedure to microsurgery, and reoperations. The postoperative course was analyzed using the Macnab criteria, supplemented by a questionnaire for follow-up. Pre- and postoperative magnetic resonance imaging volumetric analyses were performed to assess the radiologic efficacy of the technique. RESULTS: Our study population had a median age of 52 years. The median follow-up was 15 months, and the median length of hospital stay was 4 days. Median duration of surgery was 100 minutes with a median blood loss of 50 mL. Surgery was most commonly performed at the L4-L5 level (63%) and in caudally migrated disk herniations (44%). In six patients, surgery was performed for recurrent disk herniations. The procedure had to be changed to conventional microsurgery in four patients. We observed no major complications. Minor complications occurred in six patients, and in four patients a reoperation was performed. Furthermore, a significantly lower Oswestry Disability Index score (p = 0.03), a lower Short Form 8 Health Survey (SF-8) score (p = 0.001), a lower visual analog scale (VAS) lower back pain score (p = 0.03) and VAS leg pain score (p = 0.0008) at the 12-month follow-up were observed in comparison with the preoperative examination. In MRI volumetry, we detected a median postoperative volume reduction of the disk herniation of 57.1% (p = 0.02). CONCLUSIONS: The transforaminal endoscopic sequestrectomy can be safely implemented in a university hospital setting in selected patients with primary and recurrent lumbar disk herniations, and it leads to good clinical and radiologic results. However, learning curve, caseload, and residents' microsurgical training requirements clearly affect the implementation process.

Know Thy Selves: Learning to Understand Oneself Increases the Ability to Understand Others.

Understanding others' feelings, intentions, and beliefs is a crucial social skill both for our personal lives and for meeting the challenges of a globalized world. Recent evidence suggests that the ability to represent and infer others' mental states (Theory of Mind, ToM) can be enhanced by mental training in healthy adults. The present study investigated the role of training-induced understanding of oneself for the enhanced understanding of others. In a large-scale longitudinal study, two independent participant samples (N = 80 and N = 81) received a 3-month contemplative training. This training focused on perspective taking and was inspired by the Internal Family Systems model that conceives the self as being composed of a complex system of inner personality aspects. Specifically, participants practiced perspective taking on their own inner states by learning to identify and classify different inner personality parts. Results revealed that the degree to which participants improved their understanding of themselves-reflected in the number of different inner parts they could identify-predicted their improvements in high-level ToM performance over training. Especially the number of identified parts that were negatively valenced showed a strong relation with enhanced ToM capacities. This finding suggests a close link between getting better in understanding oneself and improvement in social intelligence.