Muscarinic Receptor Sequestration in SH-SY5Y Neuroblastoma Cells Is Inhibited when Clathrin Distribution Is Perturbed

The possibility that clathrin plays a role in the agonist-mediated sequestration of muscarinic cholinergic receptors in human SH-SY5Y neuroblastoma cells has been investigated by the application of experimental paradigms previously established to perturb clathrin distribution and receptor cycling events. Preincubation of SH-SY5Y cells under hypertonic conditions resulted in a pronounced inhibition of agonist-induced muscarinic receptor sequestration (70–80% at 550 mOsm), which was reversed when cells were returned to isotonic medium. Depletion of intracellular K + or acidification of the cytosol also resulted in >80% inhibition of muscarinic receptor sequestration. Under conditions of hypertonicity, depletion of intracellular K + , or acidification of cytosol, muscarinic receptor-stimulated phosphoinositide hydrolysis and Ca 2+ signaling events were either unaffected or markedly less inhibited than receptor sequestration. That these same experimental conditions did perturb clathrin distribution was verified by immunofluorescence studies. Hypertonicity and depletion of intracellular K + resulted in a pronounced accumulation of clathrin in the perinuclear region, whereas acidification of the cytosol resulted in the appearance of microaggregates of clathrin throughout the cytoplasm and at the plasma membrane. The results are consistent with the possibility that muscarinic receptors in SH-SY5Y cells are endocytosed via a clathrin-dependent mechanism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66348/1/j.1471-4159.1996.66010186.x.pd

The Interactions between Nanoparticles and the Innate Immune System from a Nanotechnologist Perspective

Inflamació; Immunitat innata; NanopartículesInflamación; Inmunidad innata; NanopartículasInflammation; Innate immunity; NanoparticlesThe immune system contributes to maintaining the body’s functional integrity through its two main functions: recognizing and destroying foreign external agents (invading microorganisms) and identifying and eliminating senescent cells and damaged or abnormal endogenous entities (such as cellular debris or misfolded/degraded proteins). Accordingly, the immune system can detect molecular and cellular structures with a spatial resolution of a few nm, which allows for detecting molecular patterns expressed in a great variety of pathogens, including viral and bacterial proteins and bacterial nucleic acid sequences. Such patterns are also expressed in abnormal cells. In this context, it is expected that nanostructured materials in the size range of proteins, protein aggregates, and viruses with different molecular coatings can engage in a sophisticated interaction with the immune system. Nanoparticles can be recognized or passed undetected by the immune system. Once detected, they can be tolerated or induce defensive (inflammatory) or anti-inflammatory responses. This paper describes the different modes of interaction between nanoparticles, especially inorganic nanoparticles, and the immune system, especially the innate immune system. This perspective should help to propose a set of selection rules for nanosafety-by-design and medical nanoparticle design.This research was funded by the EU Commission H2020 project PANDORA (GA 671881; to D.B., P.I. and V.P.). Additional funds were provided by the EU Commission H2020 project ENDONANO (GA 812661; to P.I. and D.B.), the Italian MIUR InterOmics Flagship projects MEMORAT and MAME (to D.B. and P.I.), the Italian MIUR/PRIN-20173ZECCM (to P.I.), the CAS President’s International Fellowship Programme (PIFI; award 2020VBA0028; to D.B.), Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) (RTI2018-099965-B-I00, AEI/FEDER, UE), and Generalitat de Catalunya (2017-SGR-1431) (V.P.)

Im Spannungsfeld zwischen «safety first» und «patient first»: Freiheitseinschränkende Massnahmen im Akutspital

Bei selbst- oder fremdgefährdendem Verhalten können im Akutspital freiheitseinschränkende Massnahmen (FEM) unvermeidlich sein, um das Wohl und die Interessen betroffener und beteiligter Personen zu schützen. Handlungsleitende Vorgaben aus dem ethischen und rechtlichen Bereich sehen primär personenbezogene Gründe vor, die eine Einschränkung der Freiheit rechtfertigen. In der Praxis spielen jedoch auch kontextbezogene Gründe eine Rolle. Vor diesem Hintergrund zeigt unser Beitrag das Spannungsfeld zwischen rechtlichen Vorgaben, ethischen Orientierungen und klinischer Praxis im Kontext eines Schweizer Universitätsspitals auf. Wir beschreiben Strategien für den Umgang mit diesem Spannungsfeld. Zentral ist die Sensibilisierung der Fachpersonen für den Ausnahmecharakter der FEM. Ebenso erweisen sich die Transparenz des Entscheidungsprozesses und die Nachvollziehbarkeit der Dokumentation bzw. Evaluation als wichtig

Periprosthetic joint infections in femoral neck fracture patients treated with hemiarthroplasty – should we use antibiotic-loaded bone cement?

BACKGROUND Hemiarthroplasty is the most common treatment in elderly patients with displaced intra-capsular femoral neck fracture (FNF). Prosthetic joint infection (PJI) is one of the most feared and frequent complications post-surgery because of the frail health status of these patients and the need for fast track surgery. Therefore, priorities should lie in effective preventive strategies to mitigate this burden. AIM To determine how much the implementation of the routine use of antibiotic-loaded bone cement (ALBC) as a relatively easy-to-apply amendment to the surgical practice reduces the infection rate in our hemiarthroplasty cohort. METHODS We retrospectively assessed all demographic, health status and treatment-related data of our FNF patients undergoing cemented hemiarthroplasty in the period from 2011 to 2017; 241 patients were further analyzed after exclusion of patients with cancer-related sequelae and those who died before the end of the 1-year observation period. The PJI rate as diagnosed on basis of the Musculoskeletal Infection Society (MSIS) criteria 2011 was determined for each included patient and compared in function of the bone cement used for hip stem fixation. Patients were split into a group receiving a plain bone cement in the period from January 2011 to June 2013 (non-ALBC group) and into a group receiving an ALBC in the period July 2013 to December 2017 (ALBC group). Data analysis was performed with statistical software. We further calculated the cost-efficacy of the implementation of routine use of ALBC in the second group balancing the in-hospital infection related treatment costs with the extra costs of use of ALBC. RESULTS In total 241 FNF patients who received cemented hemiarthroplasty in the period from January 2011 to January 2017 were eligible for inclusion in this retrospective study. There were 8 PJI cases identified in the ALBC group among n = 94 patients, whereas 28 PJI cases were observed in the non-ALBC group among n = 147 patients. The statistical analysis showed an infection risk reduction of 55.3% (in particular due to the avoidance of chronic delayed infections) in the ALBC group (95%CI: 6.2%-78.7%; P = 0.0025). The cost-evaluation analysis demonstrated a considerable cost saving of 3.500 € per patient, related to the implementation of routine use of ALBC in this group. CONCLUSION Use of ALBC is a potent infection preventive factor in FNF patients receiving cemented hemiarthroplasties. It was further found to be highly cost-effective.post-print314 K

The Grizzly, April 13, 2006

Relay a Success • New Healthcare Scholarship Available • Lurking Beneath the Skin: Scabies Infection • Day of Museums • Shopping with Eco-labels • Airband a Hit • Opinions: Drawing the Line: Moral Predicament of Abortion, Part II • Importance of CoSA: A Message • Bears Battle Back • Real Deal on Steroidshttps://digitalcommons.ursinus.edu/grizzlynews/1712/thumbnail.jp

The Grizzly, February 16, 2006

Hoodoo Man Arthur Flowers Delivers Captivating Speech at Ursinus • USGA Holds First Meeting of Semester • Francophone Film Festival: Almost Peaceful • Georgetown Professor to Lecture at Ursinus • Getting to Know Your Glands • Spiritual Experiences in Paris • Meet the New Director of Facilities Services and Keep Current with Bomberger Renovations • Recycling Myths Revealed • Retraction on Parking Article • Broken Social Scene a Must Have for Indie Fans • Lone Senior Walks Off a Winnerhttps://digitalcommons.ursinus.edu/grizzlynews/1706/thumbnail.jp

The Grizzly, April 27, 2006

Full Auditorium Discusses Solutions to Diversity Issues at Forum • A Senior Reflects on Her Ursinus Experience • Annual Student Art Show Opens • Crowding First Base • One Last Look Back • Students\u27 Artwork Featured Permanently in Myrin Library • Exploring the Nature of Suburban Sprawl • Opinions: Unnecessary Police Watch; Organic Obsession • Year in Review, Dynasties and Disappointmentshttps://digitalcommons.ursinus.edu/grizzlynews/1714/thumbnail.jp

Absence of chronic hepatitis E in a German cohort of common variable immunodeficiency patients

Cases of chronic or prolonged hepatitis E virus (HEV) infections have been described in solid organ transplant recipients, HIV infected patients and in patients with malignancies or idiopathic CD4+ T lymphopenia. It is unknown if HEV infection also takes chronic courses in patients with common variable immunodeficiency (CVID). We studied a cohort of 73 CVID patients recruited in a low endemic Central European country. None of the subjects tested positive for HEV RNA or anti-HEV IgG. Immunoglobulin transfusions (n=10) tested negative for HEV RNA but all were anti-HEV positive. To verify that such pooled blood products contain anti-HEV protective antibodies we measured the anti-HEV IgG optical density (OD) values in patients before and after transfusion. Anti-HEV OD values increased after infusion but did not reach the cut-off considered as positive. Thus, chronic HEV infections seem to be rare events in CVID patients in Germany. Commercially available immuno globulin infusions contain anti HEV antibodies and may contribute to protection from HEV infectio