Über den Zusammenhang zwischen Serum-Testosteron und dem Schweregrad der Psoriasis vulgaris bei Männern

Die häufig in Schüben verlaufende Psoriasis stellt eine chronisch entzündliche Dermatose dar, die mit verschiedenen Komorbiditäten - wie dem Metabolischen Syndrom - assoziiert wurde. Eine Koinzidenz der Psoriasis und erniedrigten Serum-Testosteronwerten im Rahmen eines Hypogonadismus wurde ebenfalls postuliert, jedoch bislang nicht systematisch untersucht. Übergeordnetes Ziel dieser Studie war deswegen die Untersuchung von Serum-Testosteronwerten bei Männern mit Psoriasis und der Bezug zum Schweregrad der Erkrankung. Bei 53 männlichen Psoriasis-Patienten wurden prospektiv nach schriftlichem Einverständnis das Gesamt-Testosteron und freie Testosteron bestimmt. Zudem wurden Komorbiditäten erfasst. Der Schweregrad der Psoriasis wurde durch den Psoriasis area and severity index (PASI) ermittelt. Die Studie wurde von der Ethikkommission der Universität Bonn genehmigt. Bei 42% der untersuchten männlichen Psoriasis-Patienten kamen erniedrigte Testosteronwerte zur Darstellung. Es zeigte sich eine signifikante inverse Korrelation sowohl des Gesamt-Testosterons als auch des freien Testosterons zum PASI (jeweils r = -0,3; p Psoriasis bei Männern kann einhergehen mit erniedrigtem Testosteron. Ob es sich dabei um ein Epiphänomen handelt oder ob diese Gruppe von einer Hormonsubstitution in Bezug auf die Psoriasis profitieren, müssen weitere Studien zeigen

Chronic thoracic hemisection spinal cord injury in adult rats induces a progressive decline in transmission from uninjured fibers to lumbar motoneurons

Although most spinal cord injuries are anatomically incomplete, only limited functional recovery has been observed in people and rats with partial lesions. To address why surviving fibers cannot mediate more complete recovery, we evaluated the physiological and anatomical status of spared fibers after unilateral hemisection (HX) of thoracic spinal cord in adult rats. We made intracellular and extracellular recordings at L5 (below HX) in response to electrical stimulation of contralateral white matter above (T6) and below (L1) HX. Responses from T6 displayed reduced amplitude, increased latency and elevated stimulus threshold in the fibers across from HX, beginning 1-2 weeks after HX. Ultrastructural analysis revealed demyelination of intact axons contralateral to the HX, with a time course similar to the conduction changes. Behavioral studies indicated partial recovery which arrested when conduction deficits began. These findings suggest a chronic pathological state in intact fibers and necessity for prompt treatment to minimize it

Development Concepts for Mars Ascent Vehicle (MAV) Solid and Hybrid Vehicle Systems

The Advanced Concepts Office (ACO) at Marshall Space Flight Center (MSFC) has conducted ongoing studies and trades into options for both hybrid and solid vehicle systems for potential Mars Ascent Vehicle (MAV) concepts for the Jet Propulsion Laboratory (JPL). Two MAV propulsion options are being studied for use in a potential Mars Sample Retrieval (MSR) campaign. The following paper describes the current concepts for hybrid and solid propulsion vehicles for MAV as part of a potential MSR campaign, and provides an overview of the ongoing studies and trades for both hybrid and solid vehicle system concepts. Concepts and options under consideration for vehicle subsystems include reaction control system (RCS), separation, and structures will be described in terms of technology readiness level (TRL), benefit to the vehicle design, and associated risk. A hybrid propulsion system, which uses a solid fuel core and liquid oxidizer, is currently being developed by JPL with support from MSFC. This type of hybrid propulsion vehicle would allow the MAV to be more flexible at the cost of higher complexity, in contrast to the solid propulsion vehicle that is simpler, but allows less flexibility. The solid propulsion vehicle study performed by MSFC in 2018 further refined the solid propulsion system sizing as well as added definition to vehicle subsystem concepts, including the RCS, structures and configuration, interstage and separation, aerodynamics, and power/avionics. The studies were performed using an iterative concept design methodology, engaging subject matter experts from across MSFCs propulsion and vehicle systems disciplines as well as seeking trajectory feedback from analysts at JPL

Differential effects of anti-Nogo-A antibody treatment and treadmill training in rats with incomplete spinal cord injury

Locomotor training on treadmills can improve recovery of stepping in spinal cord injured animals and patients. Likewise, lesioned rats treated with antibodies against the myelin associated neurite growth inhibitory protein, Nogo-A, showed increased regeneration, neuronal reorganization and behavioural improvements. A detailed kinematic analysis showed that the hindlimb kinematic patterns that developed in anti-Nogo-A antibody treated versus treadmill trained spinal cord injured rats were significantly different. The synchronous combined treatment group did not show synergistic effects. This lack of synergistic effects could not be explained by an increase in pain perception, sprouting of calcitonin gene-related peptide (CGRP) positive fibres or by interference of locomotor training with anti-Nogo-A antibody induced regeneration and sprouting of descending fibre tracts. The differential mechanisms leading to behavioural recovery during task-specific training and in regeneration or plasticity enhancing therapies have to be taken into account in designing combinatorial therapies so that their potential positive interactive effects can be fully expresse

Nogo-A expressed in Schwann cells impairs axonal regeneration after peripheral nerve injury

Înjured axons in mammalian peripheral nerves often regenerate successfully over long distances, in contrast to axons in the brain and spinal cord (CNS). Neurite growth-inhibitory proteins, including the recently cloned membrane protein Nogo-A, are enriched in the CNS, in particular in myelin. Nogo-A is not detectable in peripheral nerve myelin. Using regulated transgenic expression of Nogo-A in peripheral nerve Schwann cells, we show that axonal regeneration and functional recovery are impaired after a sciatic nerve crush. Nogo-A thus overrides the growth-permissive and -promoting effects of the lesioned peripheral nerve, demonstrating its in vivo potency as an inhibitor of axonal regeneration

Building a Personal Protective Equipment Monitor Team as Part of a Comprehensive COVID-19 Prevention Strategy

We instituted Personal Protective Equipment (PPE) Monitors as part of our care of COVID-19 patients in high-risk zones. PPE Monitors aided healthcare personnel (HCP) in donning and doffing, which contributed to nearly zero transmission of COVID-19 to HCP, despite their care of over 1400 COVID-19 patients

Mucosal Immunization of Cynomolgus Macaques with the VSVΔG/ZEBOVGP Vaccine Stimulates Strong Ebola GP-Specific Immune Responses

(ZEBOV) produces a lethal viral hemorrhagic fever in humans and non-human primates.We demonstrate that the VSVΔG/ZEBOVGP vaccine given 28 days pre-challenge either intranasally (IN), orally (OR), or intramuscularly (IM) protects non-human primates against a lethal systemic challenge of ZEBOV, and induces cellular and humoral immune responses. We demonstrated that ZEBOVGP-specific T-cell and humoral responses induced in the IN and OR groups, following an immunization and challenge, produced the most IFN-γ and IL-2 secreting cells, and long term memory responses.We have shown conclusively that mucosal immunization can protect from systemic ZEBOV challenge and that mucosal delivery, particularly IN immunization, seems to be more potent than IM injection in the immune parameters we have tested. Mucosal immunization would be a huge benefit in any emergency mass vaccination campaign during a natural outbreak, or following intentional release, or for mucosal immunization of great apes in the wild

Restricting Glycolysis Preserves T Cell Effector Functions and Augments Checkpoint Therapy

Tumor-derived lactic acid inhibits T and natural killer (NK) cell function and, thereby, tumor immunosurveillance. Here, we report that melanoma patients with high expression of glycolysis-related genes show a worse progression free survival upon anti-PD1 treatment. The non-steroidal anti-inflammatory drug (NSAID) diclofenac lowers lactate secretion of tumor cells and improves anti-PD1-induced T cell killing in vitro. Surprisingly, diclofenac, but not other NSAIDs, turns out to be a potent inhibitor of the lactate transporters monocarboxylate transporter 1 and 4 and diminishes lactate efflux. Notably, T cell activation, viability, and effector functions are preserved under diclofenac treatment and in a low glucose environment in vitro. Diclofenac, but not aspirin, delays tumor growth and improves the efficacy of checkpoint therapy in vivo. Moreover, genetic suppression of glycolysis in tumor cells strongly improves checkpoint therapy. These findings support the rationale for targeting glycolysis in patients with high glycolytic tumors together with checkpoint inhibitors in clinical trials

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)