Serotonin Reduction in Post-acute Sequelae of Viral Infection

Post-acute sequelae of COVID-19 (PASC, Long COVID ) pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes

Promising mid-term results of total hip arthroplasties using an uncemented lateral-flare hip prosthesis: a clinical and radiographic study

The clinical results after total hip replacements using noncemented stems have shown considerable variability over the years; the design and characteristics of the implant seemed to play a role in explaining this fact. The purpose of this paper is to report the clinical, radiographic and densitometry results of total hip arthroplasties using a stem designed for noncemented implantation and to engage and load the femur proximally. Fifty-eight consecutive patients (62 hips) followed for an average of 4.3 years (range 36–70 months) were clinically and radiographically followed up at three weeks, three months, six months, one year, and yearly thereafter. The average pre-operative Harris hip score was 49 increasing to 98 at the latest follow-up. There were no cases of aseptic or septic loosening. The average subsidence at three years was 0.45 mm (SD ± 0.36 mm). Radiographically all hips were classified as stable, and evident changes compatible with new bone apposition were observed in 64% of the cases. The extended proximal geometry of the device seems to favour initial and secondary stability as reflected by the low subsidence values over time. The maintenance of periprosthetic bone stock and the absence of stress shielding can be explained by the predominantly proximal loading pattern of the stem

Weak Functional Coupling of the Melanocortin-1 Receptor Expressed in Human Adipocytes

The melanocortin (MC) receptor type-1 (MC1-R) is the only one of the five MC receptor subtypes expressed in human adipose tissue explants, human mesenchymal stem cells (MSCs), and MSC-derived adipocytes. Following our recent expression studies (Obesity 2007, 15, 40-49), we now investigated the functional role of MC1-R in these tissues and cells to deduce the coupling state of MC1-R to intracellular output signals in human fat cells and tissue. Expression of MC1-R by undifferentiated and differentiated MSCs was quantified by real-time TaqMan PCR. Intracellular output signals (cAMP, lipolysis, secretion of IL-6, IL-10, and TNF-alpha), as well as effects on the metabolic rate and proliferation of human MSCs were analyzed by standard assays, exposing undifferentiated and differentiated MSCs and, in part, human adipose tissue explants to the potent MC1-R agonist, [Nle(4), D-Phe(7)]-alpha-MSH (NDP-MSH). This agonist induced a weak cAMP signal in MSC-derived adipocytes. However, it did not affect lipolysis in these cells or in adipose tissue explants, nor did it modulate cytokine release and mRNA expression of IL-6, IL-8, and TNF-alpha upon LPS stimulation. In undifferentiated MSCs, NDP-MSH did not alter the metabolic rate, but it showed a significant antiproliferative effect. Therefore, it appears that MC1-R-effector coupling in (differentiated) human adipocytes is too weak to induce a regulatory effect on lipolysis or inflammation; by contrast, MC1-R stimulation in undifferentiated MSCs induces an inhibitory signal on cell proliferation