Thomsenbladt3359
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Acid-sensing ion channel 3 (ASIC3) upregulation has been reported in dorsal root ganglion neurons after incision and contributes to postoperative nociception. This study hypothesized that upregulation of ASIC3 in incised tissues is induced by nerve growth factor through the phosphoinositide 3-kinase/protein kinase B signaling pathway.
A plantar incision model was established in adult male and female Sprague-Dawley rats. ASIC3 was inhibited by APETx2 treatment, small interfering RNA treatment, or ASIC3 knockout. Sciatic nerve ligation was performed to analyze ASIC3 transport. A nerve growth factor antibody and a phosphoinositide 3-kinase inhibitor were used to investigate the mechanism by which nerve growth factor regulates ASIC3 expression.
Acid-sensing ion channel 3 inhibition decreased incisional guarding and mechanical nociception. ASIC3 protein levels were increased in skin and muscle 4 h after incision (mean ± SD 5.4 ± 3.2-fold in skin, n = 6, P = 0.001; 4.3 ± 2.2-fold in muscle, n = 6, P = 0.001). Sciatic nerve ligation revealed bidirectional ASIC3 transport. Nerve growth factor antibody treatment inhibited the expression of ASIC3 (mean ± SD antibody 2.3 ± 0.8-fold vs. vehicle 4.9 ± 2.4-fold, n = 6, P = 0.036) and phosphorylated protein kinase B (mean ± SD antibody 0.8 ± 0.3-fold vs. vehicle 1.8 ± 0.8-fold, n = 6, P = 0.010) in incised tissues. Intraplantar injection of nerve growth factor increased the expression of ASIC3 and phosphorylated protein kinase B. ASIC3 expression and incisional pain-related behaviors were inhibited by pretreatment with the phosphoinositide 3-kinase inhibitor LY294002.
Acid-sensing ion channel 3 overexpression in incisions contributes to postoperative guarding and mechanical nociception. selleck chemicals Bidirectional transport of ASIC3 between incised tissues and dorsal root ganglion neurons occurs through the sciatic nerve. Nerve growth factor regulates ASIC3 expression after plantar incision through the phosphoinositide 3-kinase/protein kinase B signaling pathway.
Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a newly described condition. It has a spectrum of presentations proposed to occur as part of a post-infectious immune response. We report the first case of PIMS-TS in a child on established anti-Tumor Necrosis Factor-alpha (anti-TNF-α) therapy; a 10 year-old girl with ulcerative colitis treated with infliximab. The patient had 6-weeks of daily fever with mucocutaneous, gastrointestinal, renal and hematologic involvement. Biomarkers of hyperinflammation were present including hyperferritinaemia (up to 691 µ/L; normal 15-80 µg/L), C-reactive protein (CRP) (>100mg/L for >10 days, normal 0-5 mg/L), erythrocyte sedimentation rate (ESR) consistently >100mm/hr (normal 0-15 mm/hr), raised white cell count with neutrophilia, elevated D-dimer and lactate dehydrogenase (LDH), anaemia and Mott cells on bone marrow analysis. Extensive investigations for alternative diagnoses for pyrexia of unknown origin (PUO) were negative. The condition was refractory to treatment with intravenous immunoglobulin (IVIG) but improved within 24hrs of high dose methylprednisolone. Infliximab treatment followed and the patient has remained well at follow up. Polymerase chain reaction (PCR) and serology for SARS-CoV-2 were negative. Current series report such negative findings in up to half of cases. The patient experienced a milder clinical phenotype without cardiac involvement, shock or organ failure. Accepting the wide spectrum of PIMS-TS presentations, it is possible that prior anti-TNF-α therapy may have attenuated the disease course. Given the uncertainty around therapeutic strategies for PIMS-TS this case supports the need for further investigation into continuing infliximab as a treatment option for the condition.
A smaller lumbar multifidus (LM) muscle was reported to be a strong predictor of lower limb injury in professional Australian Football League players. However, despite the high prevalence of low back pain (LBP) and lower limb injury in rugby players, their LM characteristics have yet to be explored.
To (1) examine LM characteristics in male and female university rugby players and their possible associations with LBP and lower limb injury and (2) investigate the relationship between LM characteristics and body composition in this group of athletes.
Cross-sectional study.
University research center.
Thirty-four university rugby players (20 women, 14 men).
Ultrasound measurements of LM cross-sectional area (CSA), thickness, and percentage change in thickness during contraction were obtained bilaterally, at the L5-S1 level, in prone and standing positions. Body composition measures were obtained using dual-energy x-ray absorptiometry. Self-reported questionnaires were used to obtain LBP and lower limbts further investigation. Our findings also provide preliminary evidence of an association among LM morphology, LBP, and lower limb injury in university rugby players.Single-cell RNA sequencing (scRNA-seq) is a burgeoning field where experimental techniques and computational methods have been under rapid evolution in the past six years. These technological advances have allowed biomedical researchers to identify new cell types, delineate cell sub-populations, and infer cell differentiation trajectories in various tissue samples. Among the important features extractable from scRNA-seq data, the predominant ones are individual genes' expression levels in single cells. Most analyses require a preprocessing step that converts a scRNA-seq dataset into a count matrix, where rows correspond to cells (or genes), columns correspond to genes (or cells), and entries are counts, i.e. a count is the number of sequenced reads or uniquely mapped identifiers (UMIs) mapped to a gene in a cell. Single-cell count matrices are highly sparse; for example, a typical matrix constructed from a droplet-based dataset may have >90% of counts as zeros.