A cross-sectional comparison of performance, neurophysiological and MRI outcomes of responders and non-responders to fampridine treatment in multiple sclerosis - An explorative study

OBJECTIVE: To compare baseline physical and cognitive performance, neurophysiological, and magnetic resonance imaging (MRI) outcomes and examinetheir interrelationship inparticipants with Multiple Sclerosis (MS), already established aseither responder or non-responder to Fampridine treatment, andto examine associationswiththe expanded disability status scale (EDSS) and 12-item MS walking scale (MSWS-12). METHODS: Baseline data from an explorative longitudinal observational study were analyzed. Participants underwent the Timed 25-Foot Walk Test (T25FW), Six Spot Step Test (SSST), Nine-Hole Peg Test, Five Times Sit-to-Stand Test, Symbol Digit Modalities Test (SDMT), neurophysiological testing, including central motor conduction time (CMCT), peripheral motor conduction time (PMCT), motor evoked potential (MEP) amplitudesand electroneuronographyof the lower extremities, and brain MRI (brain volume, number and volume of T2-weighted lesions and lesion load normalized to brain volume). RESULTS: 41 responders and 8 non-responders were examined. There were no intergroup differences inphysical performance, cognitive, neurophysiological, andMRI outcomes (p > 0.05).CMCT was associated withT25FW, SSST, EDSS, and MSWS-12,(p < 0.05). SDMT was associated with the number and volume of T2-weighted lesions, and lesion load normalized to brain volume (p < 0.05). CONCLUSION: No differences were identified between responders and non-responders to Fampridine treatment regarding physical and cognitive performance, neurophysiological or MRI outcomes. The results call for cautious interpretation and further large-scale studies are needed to expand ourunderstanding of underlying mechanisms discriminating Fampridine responders and non-responders.CMCT may be used as a marker of disability and walking impairment, while SDMT was associated with white matter lesions estimated by MRI. ClinicalTrials.gov identifier: NCT03401307

Local infusion of Staphylococcus aureus into the porcine internal carotid artery as a model of sepsis-related brain abscesses - A pilot study

Brain pathology is an important aspect of human sepsis but is difficult to study in human patients. Therefore, animal models of sepsis-related brain pathology are needed. As pigs mirror multiple aspects of sepsis-related brain pathology in humans, this makes the pig a potentially suitable model.&nbsp; Unfortunately, models of sepsis in pigs are difficult to manage due to the accompanying massive systemic inflammatory response. To overcome these difficulties we designed a model in pigs of brain bacteremia established by local brain infusion in order to evaluate if this approach could reduce the systemic responses but still reflect the brain pathology of sepsis in humans. As a pilot study to obtain basic knowledge, we evaluated two methods of local infusion: long term infusion (60 minutes) of Staphylococcus aureus suspended in saline and, short-term infusion (10 minutes) of S. aureus embedded in autologous microthrombi. The study revealed: 1) bacteria suspended in saline as well as embedded in microthrombi can pass through the rete mirabile and thereby cause local brain bacteremia; 2) despite the high dose of S. aureus used for infusion, only mild clinical signs developed; and 3) despite the mild clinical signs, one pig had developed a brain microabscess by 48 h after infusion. The brain pathology present in this pig thereby reflected human cases of S. aureus-sepsis with microabscess formation as the predominant lesion. In addition, the abscess morphology mirrored previously observed microabscesses in experimental porcine S. aureus sepsis models

GLP−1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading

BackgroundGLP‐1 (glucagon‐like peptide‐1) receptor agonists exert beneficial long‐term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP‐1 depends on GLP‐1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP‐1 increases renal medullary perfusion in healthy humans.Methods and ResultsHealthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1‐hour infusion of either GLP‐1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R2*), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP‐1 infusion increased medullary perfusion (32±7%, P<0.001) and cortical perfusion (13±4%, P<0.001) compared with placebo. Here, NaCl infusion decreased medullary perfusion (−5±2%, P=0.007), whereas cortical perfusion remained unchanged. R2* values increased by 3±2% (P=0.025) in the medulla and 4±1% (P=0.008) in the cortex during placebo, indicative of decreased oxygenation, but remained unchanged during GLP‐1. Blood flow in the renal artery was not altered significantly by either intervention.ConclusionsGLP‐1 increases predominantly medullary but also cortical perfusion in the healthy human kidney and maintains renal oxygenation during NaCl loading. In perspective, suppression of angiotensin II by GLP‐1 may account for the increase in regional perfusion

Prenatal exposure to perfluoroalkyl substances and anogenital distance at 3 months of age in a Danish mother-child cohort

In the Odense child cohort, serum concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 638 pregnant women. Birth weight, head and abdominal circumferences and gestational age were determined. Anogenital distance (AGD), the distance from the anus to the genital organs, and penile width were measured 3 months after expected date of birth in 511 children. PFOS, PFHxS, PFNA and PFDA were associated with a decreased AGD in girls (p-trend < 0.05) after adjusting for age and weight-for-age standard deviation score. PFOS in the highest quartile was associated with a 2.8 mm (95% confidence intervals -4.5; -1.1) reduction in AGD in girls. No such tendencies were seen in boys. However, a tendency toward increased birth weight in girls and reduced birth weight in boys suggests that sex-dimorphic effects may occur from endocrine disrupting effects of these substances

A pig model of acute Staphylococcus aureus induced pyemia

<p>Abstract</p> <p>Background</p> <p>Sepsis caused by <it>Staphylococcus aureus </it>constitutes an important cause of morbidity and mortality in humans, and the incidence of this disease-entity is increasing. In this paper we describe the initial microbial dynamics and lesions in pigs experimentally infected with <it>S. aureus</it>, with the aim of mimicking human sepsis and pyemia.</p> <p>Methods</p> <p>The study was conducted in anaesthetized and intravenously inoculated pigs, and was based on bacteriological examination of blood and testing of blood for IL-6 and C-reactive protein. Following killing of the animals and necropsy bacteriological and histological examinations of different organs were performed 4, 5 or 6 h after inoculation.</p> <p>Results</p> <p>Clearance of bacteria from the blood was completed within the first 2 h in some of the pigs and the highest bacterial load was recorded in the lungs as compared to the spleen, liver and bones. This probably was a consequence of both the intravenous route of inoculation and the presence of pulmonary intravascular macrophages. Inoculation of bacteria induced formation of acute microabscesses in the lungs, spleen and liver, but not in the kidneys or bones. No generalized inflammatory response was recorded, i.e. IL-6 was not detected in the blood and C-reactive protein did not increase, probably because of the short time course of the study.</p> <p>Conclusion</p> <p>This study demonstrates the successful induction of acute pyemia (microabscesses), and forms a basis for future experiments that should include inoculation with strains of <it>S. aureus </it>isolated from man and an extension of the timeframe aiming at inducing sepsis, severe sepsis and septic shock.</p

Chronic fatigue syndromes: real illnesses that people can recover from

The ‘Oslo Chronic Fatigue Consortium’ consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation. Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them