The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9.

Siglec-9 is a sialic-acid-binding lectin expressed predominantly on myeloid cells. Aberrant glycosylation occurs in essentially all types of cancers and results in increased sialylation. Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. Moreover, MUC1-ST induced macrophages to display a tumor-associated macrophage (TAM)-like phenotype, with increased expression of the checkpoint ligand PD-L1. Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. This work defines a critical role for aberrantly glycosylated MUC1 and identifies an activating pathway that follows engagement of Siglec-9.

Herbal remedies as a potential cause of hypoadrenalism.

A 37-year-old woman presented with nausea, vomiting and headache. She was found to be profoundly hyponatraemic with a sodium of 121 mmol/L, which deteriorated following a fluid challenge. An initial hyponatraemia screen identified adrenal insufficiency, with cortisol of 48 nmol/L. History confirmed she had been taking the herbal plant, ashwagandha. After 3 days of fluid restriction and steroid replacement, her sodium returned to normal (139 mmol/L). This article reviews the possible harmful effects of over-the-counter herbal remedies and highlights the importance of considering a wide differential diagnosis in patients presenting with non-specific symptoms.

Competition Anxiety in Combat Sports and the Importance of Mental Toughness.

Combat sports require participants to engage in potentially dangerous forms of contact-based competition. Pressure to succeed, coupled with the risk of severe injury can induce significant levels of anxiety, which if uncontrolled, can negatively impact performance and possibly promote unsporting conduct. The present study examined competitive anxiety levels of combat sports athletes and determined whether self-reported scores were associated with mental toughness and Sportspersonship attitudes. A cross-sectional survey design was used whereby participants (N = 194) completed a battery of questionnaires measuring competitive combat sport experiences, demographic details, Sportspersonship traits (compliance towards rules, respect for opponents, and game perspective), and competition anxiety (somatic, cognitive, and self-confidence; reported retrospectively). Results suggest that mentally tough athletes experience lower levels of cognitive and somatic anxiety, and higher self-confidence, prior to competitions. Findings also found that athletes endorsing more altruistic and respectful attitudes in sport (Sportspersonship) reported higher levels of competition anxiety. The findings demonstrate that mental toughness is allied to positive attributes and could potentially be operationalized to improve both the retention and performance of combat sports athletes. Thus, the authors advocate the use of mental toughness coaching interventions within combat sports.