In-depth investigations into Salmonella infection sources, reservoirs, and intervention measures in herds with a high hygiene level

The paper describes the in-depth analysis of the reasons for an extreme high Salmonella load of a high-health and well-managed pork production system and the measures that were taken to reduce the prevalence of Salmonella antibody positive finisher pigs produced by the system. The results and experiences gained during the study are discussed

Pain Management Program in Cardiology: A Template for Application of Normalization Process Theory and Social Marketing to Implement a Change in Practice Quality Improvement

Quality improvement plays a major role in healthcare, and numerous approaches have been developed to implement changes. However, the reasons for success or failure of the methods applied often remains obscure. Normalization process theory, recently developed in sociology, provides a flexible framework upon which to construct quality improvement. We sought to determine if examination of a successful quality improvement project, using normalization process theory and social marketing, provided insight into implementation. We performed a retrospective analysis of the steps taken to implement a pain management program in an electrophysiology clinic. We mapped these steps, and the corresponding social marketing tools used, to elements of normalization process theory. The combination of mapping implementation steps and marketing approaches to the theory provided insight into the quality-improvement process. Specifically, examination of the steps in the context of normalization process theory highlighted barriers to implementation at individual, group, and organizational levels. Importantly, the mapping also highlighted how facilitators were able to overcome the barriers with marketing techniques. Furthermore, integration with social marketing revealed how promotion of tangibility of benefits aided communication and how process co-creation between stakeholders enhanced value. Our implementation of a pain-management program was successful in a challenging environment composed of several stakeholder groups with entrenched initial positions. Therefore, we propose that the behavior change elements of normalization process theory combined with social marketing provide a flexible framework to initiate quality improvement

Dynamic changes in the signal-averaged electrocardiogram are associated with the long-term outcomes after ablation of ischemic ventricular tachycardia

Abstract Purpose Signal-averaged ECG (SAECG) can detect inhomogeneous myocardial conduction in patients presenting with ventricular tachycardia (VT) after myocardial infarction. Radiofrequency ablation (RFCA) aims at elimination of the endocardial late potentials and non-inducibility of VT. Previously, we demonstrated that abnormal SAECG at baseline can return to normal after a successful VT ablation. The present research investigates the post-ablation changes in SAECG after RFCA of VT and their relation to the procedural long-term outcomes. Methods Thirty-three patients (31 male; age 68 ± 9 years; EF 36 ± 12%) with ischemic VT were prospectively enrolled to receive RFCA. One VT (range 1–7) per patient was ablated using substrate-guided RFCA and complete success was achieved in 28 (85%) cases. SAECG was performed before (t1), immediately after (t2), and at least 6 months (t3) after the RFCA. Results After RFCA, the amount of patients showing abnormal SAECG decreased from 82% initially (t1) to 57.6% post-interventionally (t2); P = 0.008; and remained unchanged thereafter in 57% (t3). Patients who experienced VT recurrence (VT+) during the follow-up period had broader averaged QRS (t2): (VT+) 150 ± 26 vs. (VT−) 129 ± 21 ms; P = 0.015, as well as longer LAS40 (t2): (VT+) 60 ± 26 vs. (VT−) 43 ± 18 ms; P = 0.03. Abnormal SAECG (t2) was a strong predictor for VT recurrence: HR 5.4; 95% CI 1.5–21. SAECG detected more late potentials in patients with inferior than in those with anterior scars: 95% vs. 58%; P = 0.016. Conclusions RFCA of VT in the left ventricle can improve an abnormal SAECG in some patients after myocardial infarction. Normal SAECG after RFCA of VT is associated with a lower risk for VT recurrence and death

Platelets Boost Recruitment of CD133+ Bone Marrow Stem Cells to Endothelium and the Rodent Liver-The Role of P-Selectin/PSGL-1 Interactions

Lehwald N, Duhme C, Pinchuk I, et al. Platelets Boost Recruitment of CD133+ Bone Marrow Stem Cells to Endothelium and the Rodent Liver-The Role of P-Selectin/PSGL-1 Interactions. International journal of molecular sciences. 2020;21(17): 6431.We previously demonstrated that clinical administration of mobilized CD133+ bone marrow stem cells (BMSC) accelerates hepatic regeneration. Here, we investigated the potential of platelets to modulate CD133+BMSC homing to hepatic endothelial cells and sequestration to warm ischemic livers. Modulatory effects of platelets on the adhesion of CD133+BMSC to human and mouse liver-sinusoidal- and micro- endothelial cells (EC) respectively were evaluated in in vitro co-culture systems. CD133+BMSC adhesion to all types of EC were increased in the presence of platelets under shear stress. This platelet effect was mostly diminished by antagonization of P-selectin and its ligand P-Selectin-Glyco-Ligand-1 (PSGL-1). Inhibition of PECAM-1 as well as SDF-1 receptor CXCR4 had no such effect. In a model of the isolated reperfused rat liver subsequent to warm ischemia, the co-infusion of platelets augmented CD133+BMSC homing to the injured liver with heightened transmigration towards the extra sinusoidal space when compared to perfusion conditions without platelets. Extravascular co-localization of CD133+BMSC with hepatocytes was confirmed by confocal microscopy. We demonstrated an enhancing effect of platelets on CD133+BMSC homing to and transmigrating along hepatic EC putatively depending on PSGL-1 and P-selectin. Our insights suggest a new mechanism of platelets to augment stem cell dependent hepatic repair

Investing in Threatened Species Conservation: Does Corruption Outweigh Purchasing Power?

In many sectors, freedom in capital flow has allowed optimization of investment returns through choosing sites that provide the best value for money. These returns, however, can be compromised in countries where corruption is prevalent. We assessed where the best value for money might be obtained for investment in threatened species that occur at a single site, when taking into account corruption. We found that the influence of corruption on potential investment decisions was outweighed by the likely value for money in terms of pricing parity. Nevertheless global conservation is likely to get best returns in terms of threatened species security by investing in “honest” countries than in corrupt ones, particularly those with a high cost of living

A prognostic neural epigenetic signature in high-grade glioma

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance of malignant stemcell-like cells in high-neural glioblastoma, primarily of the neural lineage. These cells are further classified as neural-progenitor-cell-like, astrocyte-like and oligodendrocyte-progenitor-like, alongside oligodendrocytes and excitatory neurons. In line with these findings, high-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature is associated with decreased overall and progression-free survival. High-neural tumors also exhibit increased functional connectivity in magnetencephalography and resting-state magnet resonance imaging and can be detected via DNA analytes and brain-derived neurotrophic factor in patients' plasma. The prognostic importance of the neural signature was further validated in patients diagnosed with diffuse midline glioma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant. High-neural gliomas likely require a maximized surgical resection approach for improved outcomes

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

In-depth investigations into Salmonella infection sources, reservoirs, and intervention measures in herds with a high hygiene level

The paper describes the in-depth analysis of the reasons for an extreme high Salmonella load of a high-health and well-managed pork production system and the measures that were taken to reduce the prevalence of Salmonella antibody positive finisher pigs produced by the system. The results and experiences gained during the study are discussed.</p