Low Endotoxin Recovery : Wiederfindung und pyrogene Aktivität von Endotoxinen in pharmazeutischen Produkten

Eine zuverlässige Überwachung bakterieller Kontaminationen ist entscheidend für die Herstellung und Sicherheit biopharmazeutischer Produkte. Die mikrobielle Sicherheit wird in der Regel (zusätzlich zu Sterilitätstests und Umweltüberwachung) durch Tests auf das Vorhandensein von Endotoxin, mit Limulus-basierten Testmethoden (BET) gewährleistet. Endotoxin dient hierbei als Indikator für potenzielle Gram-negative bakterielle Kontaminationen. Trotz einer breiten Akzeptanz des BET als Sicherheits- und Freigabetest wird dessen Anwendbarkeit seit der Entdeckung des Low-Endotoxin-Recovery (LER) Effektes intensiv diskutiert. Dieses Phänomen beschreibt die Unfähigkeit von Limulus-basierten (LAL) Methoden, Lipopolysaccharide (LPS) aufgrund eines Matrix-assoziierten Maskierungseffekts angemessen zu erkennen. Während die zugrunde liegenden Mechanismen und die Kinetik von LER-Phänomenen in bekannten Maskierungsformulierungen und in Bezug auf ihre Auswirkungen auf LAL-Systeme gut beschrieben sind, bleibt die biologische Aktivität und Pyrogenität des maskierten Endotoxins oft unbeachtet. Darüber hinaus warf die Endotoxinheterogenität die Frage auf, wie und bis zu welchem Umfang LER einerseits durch die Quelle von LPS und andererseits durch seine Wechselwirkung mit komplexen Matrizen, wie z. B. tatsächlichen pharmazeutischen Produkten, beeinflusst wird. In dieser Studie wurde die Maskierungskapazität verschiedener Pufferformulierungen sowie zugelassener pharmazeutischer Produkte untersucht und mit der Pyrogenität des maskierten Endotoxins in diesen Systemen verglichen. Dazu wurden unverdünnten Proben aufgereinigte Endotoxinpräparationen sowie Membranvesikel (OMVs, natürlich vorkommende Endotoxine) unterschiedlicher bakterieller Herkunft zugesetzt und anschließend auf Endotoxinwiederfindung und biologische Aktivität hin analysiert. Es konnte gezeigt werden, dass isoliertes LPS sowie natürlich vorkommende Endotoxine (NOE) nicht nur in künstlichen Puffersystemen, sondern auch in komplexeren Matrizen zugelassener pharmazeutischer Produkte maskiert werden. Die vorgestellten Daten veranschaulichen die große Abhängigkeit von LER in Bezug auf die Matrixzusammensetzung und die Quelle und den Ursprung des bakteriellen Endotoxins. Zusätzlich werden zwei verschiedene biophysikalische Detektionssysteme auf ihre mögliche Verwendung beim Nachweis von maskiertem Endotoxin untersucht. Neben ersten Hinweisen und vielversprechenden Ergebnissen für ihre allgemeine Anwendung im Endotoxin-Nachweis war es in dieser Studie jedoch nicht möglich, einen funktionellen Test für den Nachweis von maskiertem Endotoxin zu etablieren

El contexto de la comunicación corporativa

Communication and everything that is related to it, is suffering a massive change in the last years, the digitalization of media and tools of communication have made an impact in all the industries and how the communicate, especially on how the communicate internally...La comunicación y todo lo que se relaciona con ella, está sufriendo un cambio muy masivo en los últimos años, la digitalización de los medios y de las herramientas de comunicación han afectado todas las industrias y la manera en que se comunican, sobre todo en las maneras que se comunican internamente..

What is considered to be emotional suffering by psychotherapy patients and their therapists in Eastern versus Western Germany? : A mixed-methods study

PURPOSE This study examined what aspects of life in Eastern and Western Germany are considered by patients, therapists and society to cause (or indicate) emotional suffering so that outpatient psychotherapy is sought and warranted. METHODS In Germany, psychotherapy is covered by health insurance after patients submit an application accompanied by a written report from the therapist. We took a random sample of such applications and performed a qualitative text analysis of the reports, identifying all text units where some form of emotional suffering, distress or handicap was described. A coding system was developed based on the units, and all units were subsequently coded. The proportion of units per category was compared between reports from Western and Eastern Germany using chi-square tests. RESULTS Out of 500 randomly selected reports, 25 were from Eastern Germany. An age- and sex-matched sample from Western Germany was added. From these 50 reports, a total of 716 text units describing some form of emotional suffering were extracted (359 units from reports from Eastern Germany and 357 from Western Germany). Thirteen categories of emotional suffering emerged. In Eastern Germany, emotional suffering was considerably more frequently described in terms of somatic symptoms and in feeling nervous and tense. Patients from Western Germany were more often described as feeling depressed and hopeless, helpless, anxious and without drive (ϕ = 0.19, p = .02). CONCLUSION There is evidence that there are differences between Eastern and Western Germany in how emotional suffering is expressed and/or described

Benefit of Action Naming Over Object Naming for Visualization of Subcortical Language Pathways in Navigated Transcranial Magnetic Stimulation-Based Diffusion Tensor Imaging-Fiber Tracking

Visualization of functionally significant subcortical white matter fibers is needed in neurosurgical procedures in order to avoid damage to the language network during resection. In an effort to achieve this, positive cortical points revealed during preoperative language mapping with navigated transcranial magnetic stimulation (nTMS) can be employed as regions of interest (ROIs) for diffusion tensor imaging (DTI) fiber tracking. However, the effect that the use of different language tasks has on nTMS mapping and subsequent DTI-fiber tracking remains unexplored. The visualization of ventral stream tracts with an assumed lexico-semantic role may especially benefit from ROIs delivered by the lexico-semantically demanding verb task, Action Naming. In a first step, bihemispheric nTMS language mapping was administered in 18 healthy participants using the standard task Object Naming and the novel task Action Naming to trigger verbs in a small sentence context. Cortical areas in which nTMS induced language errors were identified as language-positive cortical sites. In a second step, nTMS-based DTI-fiber tracking was conducted using solely these language-positive points as ROIs. The ability of the two tasks’ ROIs to visualize the dorsal tracts Arcuate Fascicle and Superior Longitudinal Fascicle, the ventral tracts Inferior Longitudinal Fascicle, Uncinate Fascicle, and Inferior Fronto-Occipital Fascicle, the speech-articulatory Cortico-Nuclear Tract, and interhemispheric commissural fibers was compared in both hemispheres. In the left hemisphere, ROIs of Action Naming led to a significantly higher fraction of overall visualized tracts, specifically in the ventral stream’s Inferior Fronto-Occipital and Inferior Longitudinal Fascicle. No difference was found between tracking with Action Naming vs. Object Naming seeds for dorsal stream tracts, neither for the speech-articulatory tract nor the inter-hemispheric connections. While the two tasks appeared equally demanding for phonological-articulatory processes, ROI seeding through the task Action Naming seemed to better visualize lexico-semantic tracts in the ventral stream. This distinction was not evident in the right hemisphere. However, the distribution of tracts exposed was, overall, mirrored relative to those in the left hemisphere network. In presurgical practice, mapping and tracking of language pathways may profit from these findings and should consider inclusion of the Action Naming task, particularly for lesions in ventral subcortical regions

Bihemispheric Navigated Transcranial Magnetic Stimulation Mapping for Action Naming Compared to Object Naming in Sentence Context

Preoperative language mapping with navigated transcranial magnetic stimulation (nTMS) is currently based on the disruption of performance during object naming. The resulting cortical language maps, however, lack accuracy when compared to intraoperative mapping. The question arises whether nTMS results can be improved, when another language task is considered, involving verb retrieval in sentence context. Twenty healthy German speakers were tested with object naming and a novel action naming task during nTMS language mapping. Error rates and categories in both hemispheres were compared. Action naming showed a significantly higher error rate than object naming in both hemispheres. Error category comparison revealed that this discrepancy stems from more lexico-semantic errors during action naming, indicating lexico-semantic retrieval of the verb being more affected than noun retrieval. In an area-wise comparison, higher error rates surfaced in multiple right-hemisphere areas, but only trends in the left ventral postcentral gyrus and middle superior temporal gyrus. Hesitation errors contributed significantly to the error count, but did not dull the mapping results. Inclusion of action naming coupled with a detailed error analysis may be favorable for nTMS mapping and ultimately improve accuracy in preoperative planning. Moreover, the results stress the recruitment of both left- and right-hemispheric areas during naming

Myocardial Deformation in the Pediatric Age Group: Normal Values for Strain and Strain Rate Using 2D Magnetic Resonance Feature Tracking

Purpose To provide pediatric MR reference values for strain and strain rate for all four heart chambers. Study type Retrospective. Subjects One hundred and fifty-seven healthy children from two institutions (102 male, age 4.7-18 years). Field strength/sequence 1.5 T; balanced steady-state free precession sequence. Assessment Left ventricular (LV) global and regional longitudinal, circumferential, and radial strain and strain rate as well as right ventricular (RV) and atrial global and regional longitudinal strain and strain rate were measured in two-, three-, and four-chamber views and the short axis stack. The relationships between strain parameters and age, height, weight, and gender were investigated. Age- and height-specific centile curves and tables were created for LV strain and strain rate. For all other global strain parameters, the mean was calculated as a reference. Statistical tests Lambda-mu-sigma (LMS)-method of Cole and Green, univariable, and multivariable linear regression models. A P value <0.05 was considered to be statistically significant. Results Age, height and weight had a significant influence on LV global strain values. These parameters also showed an influence on RV strain but only in boys (girls P = 0.12) and none of the variables had a significant influence on atrial strain (P = 0.19-0.49). Gender differences were only found for RV strain values. Data conclusion Pediatric potential reference values for myocardial deformation parameters of both ventricles and atria are provided. The values may serve as a reference in future studies and clinical practice. Level of evidence 3 TECHNICAL EFFICACY: Stage 5

Surgical and functional outcome after resection of 64 petroclival meningiomas

Objective: The management of petroclival meningiomas (PCMs) remains notoriously difficult due to their close association with neurovascular structures and their complex anatomy, hence the surgical paradigm change from radical to functional resection in the past. With this study, we aimed to analyze surgical and functional outcomes of a modern consecutive series of patients with PCMs. Methods: We reviewed patient charts and imaging data of 64 consecutive patients from 2006 to 2018 with a PCM resected at our institution and compared surgical and functional outcomes between subgroups stratified by surgical approach. Results: Females comprised 67.2% of patients (n = 43), with a mean age of 55 years (median 56; range 21–84). Follow-up data were available for 68.8% and reached a mean of 42.3 months (range 1–129) with a median of 28.5 months. The mean tumor diameter was 37.3 mm (standard deviation (SD) 15.4; median 37.0). Infiltration of the cavernous sinus was observed in 34 cases (53.1%), and the lesions affected the brain stem in 28 cases (43.8%). Preoperative cranial nerve palsy was observed in 73.4% of cases; trigeminal neuropathy (42.2%), hearing loss (32.8%), and impairment of vision (18.8%) were the most common. A retrosigmoid approach was employed in 47 cases (78.1%), pterional in 10 (15.6%), combined petrosal in 2 (3.1%), and transnasal and subtemporal in 1 (1.6%). Fifteen cases (23.4%) were resected in a two-staged fashion. Gross total resection (GTR) was attempted in 30 (46.9%) cases without cavernous sinus infiltration and was achieved in 21 (70.0%) of these cases. Surgical complications occurred in 13 cases (20.3%), most commonly meningitis (n = 4; 6.3%). Postoperatively, 56 patients (87.5%) developed new cranial nerve palsy, of which 36 (63.6%) had improved or resolved on last follow up. Achieving GTR was not significantly associated with higher rates of surgical complications (chi-square; p = 0.288) or postoperative cranial nerve palsy (chi-square; p = 0.842). Of all cases, 20 (31.3%) underwent postoperative radiation. Tumor progression was observed in 10 patients (15.9%) after a mean 102 months (median 124). Conclusions: Surgical resection remains the mainstay of treatment for PCMs, with perioperative cranial neuropathies exhibiting favorable recovery rates. Most essentially, the preselection of patients with hallmarks of brain stem affection and cavernous sinus infiltration should dictate whether to strive for a functionally oriented strategy in favor of radical resection