Can exercise interventions reduce external knee adduction moment during gait? A systematic review and meta-analysis.

BACKGROUND: An increased external knee adduction moment has been identified as a factor contributing to the progression of medial knee osteoarthritis. Interventions that reduce knee adduction moment may help prevent knee osteoarthritis onset and progression. While exercise interventions have been commonly used to treat knee osteoarthritis, whether exercises can modulate knee adduction moment in knee osteoarthritis patients remains unknown. This systematic review and meta-analysis aimed to determine if exercise interventions are effective in reducing knee adduction moment during gait. METHODS: Study reports published through May 2023 were screened for pre-specified inclusion/exclusion criteria. Nine studies met the eligibility criteria and yielded 24 effect sizes comparing the reduction in knee adduction moment of the exercise intervention groups to the control groups. Moderator/experimental variables concerning characteristics of the exercise interventions and included subjects (e.g., sex, BMI, type of exercise, muscle group targeted, training volume, physical therapist supervision) that may contribute to variation among studies were explored through subgroup analysis and meta-regression. FINDINGS: The effect of exercise intervention on modulating knee adduction moment during gait was no better than control (ES = -0.004, P = 0.946). Sub-group analysis revealed that the effect sizes of studies containing only females (positive exercise effect) were significantly greater than studies containing both males and females. INTERPRETATION: Exercise may not be effective in reducing knee adduction moment during gait. Clinicians aiming to decrease knee adduction moment in patients with medial knee osteoarthritis should consider alternative treatment options. Exploring the underlying mechanism(s) regarding a more positive response to exercises in females may help design more effective exercise interventions.

Detection and modulation of capsaicin perception in the human oral cavity.

Capsaicin causes a burning or spicy sensation when this vanilloid compound comes in contact with trigeminal neurons of the tongue. This compound has low solubility in water, which presents difficulties in examining the psychophysical properties of capsaicin by standard aqueous chemosensory tests. This report describes a new approach that utilizes edible strips for delivering precise amounts of capsaicin to the human oral cavity for examining threshold and suprathreshold amounts of this irritant. When incorporated into pullulan-based edible strips, recognition thresholds for capsaicin occurred over a narrow range, with a mean value near 1 nmol. When incorporated into edible strips at suprathreshold amounts, capsaicin yielded robust intensity values that were readily measured in our subject population. Maximal capsaicin intensity was observed 20 s after strips dissolved on the tongue surface, and then decreased in intensity. Suprathreshold studies showed that complete blockage of nasal airflow diminished capsaicin perception in the oral cavity. Oral rinses with vanillin-linoleic acid emulsions decreased mean intensity values for capsaicin by approximately 75%, but only modestly affected recognition threshold values. Also, oral rinses with isointense amounts of aqueous sucrose and sucralose solutions decreased mean intensity values for capsaicin by approximately 50%. In addition, this decrease in capsaicin intensity following an oral rinse with sucrose was partially reversed by the sweet taste inhibitor lactisole. These results suggest that blockage of nasal airflow, vanillin, sucrose, and sucralose modulate capsaicin perception in the human oral cavity. The results further suggest a chemosensory link between receptor cells that detect sweet taste stimuli and trigeminal neurons that detect capsaicin.

Decreased MAPK- and PGE2-dependent IL-11 production in Gialpha2-/- colonic myofibroblasts.

Mice deficient in the G-protein alpha subunit G(i)alpha(2) spontaneously develop colitis and colon cancer. IL-11 is a pleiotropic cytokine known to protect the intestinal epithelium from injury in animal models of colitis and is produced by subepithelial myofibroblasts in response to inflammatory mediators including TGF-beta, IL-1beta, and PGE(2). Arachidonic acid release and subsequent PGE(2) production is significantly decreased in the colonic mucosa of G(i)alpha(2)-/- mice, and we hypothesized that this would affect mucosal IL-11 production. Mucosal levels of IL-11 were found to be significantly decreased in G(i)alpha(2)-/- mice despite the presence of mild colitis. Primary cultures of G(i)alpha(2)-/- intestinal and colonic myofibroblasts (IMF and CMF, respectively) produced less basal and TGF-beta or IL-1beta-stimulated IL-11 mRNA and protein than wild-type cells. Inhibitors of ERK or p38 MAPK activation dose dependently inhibited IMF and CMF IL-11 production in response to TGF-beta stimulation, whereas 16,16 dimethyl-PGE(2) and prostanoid receptor subtype-selective agonists induced IL-11 production. Treatment of animals with the EP4-specific agonist ONO-AE1-329 resulted in enhanced mucosal levels of IL-11, and increased IL-11 production by ex vivo cultured CMF. Modulation of cAMP levels produced diverging results, with enhancement of TGF-beta-induced IL-11 release in IMF pretreated with 8-Br-cAMP and inhibition in cells treated either with pertussis toxin or the PKA inhibitor H-89. These data suggest a physiological role for prostaglandins, MAPK signaling, and cAMP signaling for the production of myofibroblast-derived IL-11 in the mouse intestinal mucosa.