Structure-Based Identification and Functional Characterization of a Lipocalin in the Malaria Parasite Plasmodium falciparum

Highlights: • Crystal structure of the malaria parasite lipocalin • Comparative analysis of lipocalin superfamily members in alveolate genomes • Localization of PfLipocalin to the parasitophorous vacuole and food vacuole • Reverse genetics reveal PfLipocalin function in oxidative damage control Summary: Proteins of the lipocalin family are known to bind small hydrophobic ligands and are involved in various physiological processes ranging from lipid transport to oxidative stress responses. The genome of the malaria parasite Plasmodium falciparum contains a single protein PF3D7_0925900 with a lipocalin signature. Using crystallography and small-angle X-ray scattering, we show that the protein has a tetrameric structure of typical lipocalin monomers; hence we name it P. falciparum lipocalin (PfLCN). We show that PfLCN is expressed in the intraerythrocytic stages of the parasite and localizes to the parasitophorous and food vacuoles. Conditional knockdown of PfLCN impairs parasite development, which can be rescued by treatment with the radical scavenger Trolox or by temporal inhibition of hemoglobin digestion. This suggests a key function of PfLCN in counteracting oxidative stress-induced cell damage during multiplication of parasites within erythrocytes

Aortobronchial fistula and Listeria endograft infection after repeated T/EVAR: a rare combination

Here we present a rare combination of aortobronchial fistula and Listeria endograft infection after repeat endovascular aortic repair. Device retention, debridement and negative pressure wound therapy, in combination with suppressive antimicrobial therapy, led to satisfactory control of infection until the patient died due to another complication. The combination of an aortobronchial fistula and Listeria endograft infection has never been described before. This present case should encourage and show clinicians the importance of an interdisciplinary approach in highly difficult clinical courses

Use of Process Modelling for Optimization of Molecular Tumor Boards

In Molecular Tumor Boards, a team of experts discuss the individual therapy options of a cancer patient based on their individual molecular profile. The process—from recommendation request, through molecular diagnosis, to a personalized therapy recommendation—is complex and time-consuming. Therefore, process optimization is needed to decrease the workload of physicians and to standardize the process. For this purpose, we modeled the current workflow of the Molecular Tumor Board at the University Hospital Hamburg-Eppendorf on Service-Oriented Architecture using Business Process Modeling and Notation to highlight areas for improvement. This identified many manual tasks and an extensive workload for the physician. We then created a novel, simplified, more efficient workflow in which the physician is supported by additional software. In summary, we show that the use of Service-Oriented Architecture using Business Process Modeling and Notation for Molecular Tumor Board processes promotes rapid adaptability, standardization, interoperability, quality assurance, and facilitates collaboration

Sarcopenia, Precardial Adipose Tissue and High Tumor Volume as Outcome Predictors in Surgically Treated Pleural Mesothelioma

Background: We evaluated the prognostic value of Sarcopenia, low precardial adipose-tissue (PAT), and high tumor-volume in the outcome of surgically-treated pleural mesothelioma (PM). Methods: From 2005 to 2020, consecutive surgically-treated PM-patients having a pre-operative computed tomography (CT) scan were retrospectively included. Sarcopenia was assessed by CT-based parameters measured at the level of the fifth thoracic vertebra (TH5) by excluding fatty-infiltration based on CT-attenuation. The findings were stratified for gender, and a threshold of the 33rd percentile was set to define sarcopenia. Additionally, tumor volume as well as PAT were measured. The findings were correlated with progression-free survival and long-term mortality. Results: Two-hundred-seventy-eight PM-patients (252 male; 70.2 ± 9 years) were included. The mean progression-free survival was 18.6 ± 12.2 months, and the mean survival time was 23.3 ± 24 months. Progression was associated with chronic obstructive pulmonary disease (COPD) (p = p = 0.001), and type of surgery (p = 0.026). Three-year mortality was associated with higher patient age (p = 0.005), presence of COPD (p p = 0.015), and higher tumor-volume (p p = 0.002). While there was a negative correlation of progression-free survival and mortality with tumor volume (r = 0.281, p = 0.001 and r = −0.240, p p = 0.040). Conclusions: Sarcopenia as well as tumor volume are associated with long-term mortality in surgically treated PM-patients. Further, while there was a negative correlation of progression-free survival and mortality with tumor volume, a correlation with PAT could only be shown for epithelioid PM

Sarcopenia, Precardial Adipose Tissue and High Tumor Volume as Outcome Predictors in Surgically Treated Pleural Mesothelioma

BACKGROUND We evaluated the prognostic value of Sarcopenia, low precardial adipose-tissue (PAT), and high tumor-volume in the outcome of surgically-treated pleural mesothelioma (PM). METHODS From 2005 to 2020, consecutive surgically-treated PM-patients having a pre-operative computed tomography (CT) scan were retrospectively included. Sarcopenia was assessed by CT-based parameters measured at the level of the fifth thoracic vertebra (TH5) by excluding fatty-infiltration based on CT-attenuation. The findings were stratified for gender, and a threshold of the 33rd percentile was set to define sarcopenia. Additionally, tumor volume as well as PAT were measured. The findings were correlated with progression-free survival and long-term mortality. RESULTS Two-hundred-seventy-eight PM-patients (252 male; 70.2 ± 9 years) were included. The mean progression-free survival was 18.6 ± 12.2 months, and the mean survival time was 23.3 ± 24 months. Progression was associated with chronic obstructive pulmonary disease (COPD) (p = <0.001), tumor-stage (p = 0.001), and type of surgery (p = 0.026). Three-year mortality was associated with higher patient age (p = 0.005), presence of COPD (p < 0.001), higher tumor-stage (p = 0.015), and higher tumor-volume (p < 0.001). Kaplan-Meier statistics showed that sarcopenic patients have a higher three-year mortality (p = 0.002). While there was a negative correlation of progression-free survival and mortality with tumor volume (r = 0.281, p = 0.001 and r = -0.240, p < 0.001; respectively), a correlation with PAT could only be shown for epithelioid PM (p = 0.040). CONCLUSIONS Sarcopenia as well as tumor volume are associated with long-term mortality in surgically treated PM-patients. Further, while there was a negative correlation of progression-free survival and mortality with tumor volume, a correlation with PAT could only be shown for epithelioid PM

Structure-Based Identification and Functional Characterization of a Lipocalin in the Malaria Parasite Plasmodium falciparum

Proteins of the lipocalin family are known to bind small hydrophobic ligands and are involved in various physiological processes ranging from lipid transport to oxidative stress responses. The genome of the malaria parasite Plasmodium falciparum contains a single protein PF3D7_0925900 with a lipocalin signature. Using crystallography and small-angle X-ray scattering, we show that the protein has a tetrameric structure of typical lipocalin monomers; hence we name it P. falciparum lipocalin (PfLCN). We show that PfLCN is expressed in the intraerythrocytic stages of the parasite and localizes to the parasitophorous and food vacuoles. Conditional knockdown of PfLCN impairs parasite development, which can be rescued by treatment with the radical scavenger Trolox or by temporal inhibition of hemoglobin digestion. This suggests a key function of PfLCN in counteracting oxidative stress-induced cell damage during multiplication of parasites within erythrocytes