Tongue-Palate Interaction in Discrete and Sequential Swallowing

Historically, swallowing motor control was thought to involve a central mechanism that generated patterned responses with little use of sensory input. Although increasing evidence of peripheral modulation has altered this concept, our knowledge about the flexibility in deglutitive motor control and performance is incomplete. This study sought to gain a better understanding by examining lingual motor strategies in light of changing bolus properties (volume, consistency) and task demands (discrete vs. sequential swallowing). Specifically, the timing and patterns of tongue-palate contact and the associated changes in tongue shape and action were examined in five normal adults using simultaneous electropalatography (EPG) and ultrasound. Tasks for discrete swallowing included 5 and 30 cc of water, 5 and 30 cc of gelatin, and saliva. Tasks for sequential swallowing involved drinking 200 cc of water at normal and fast rates. Two analysis schemes were used to make timing and percent-contact measurements: segmentation of the EPG time series into four stages (prepropulsion, propulsion, full contact, withdrawal), and compartmentalization of the pseudopalate into six bins (front, central, back, lateral, medial, midline). Results showed little variation in contact pattern as a function of bolus property or subject, suggesting considerable stereotypy in lingual motor strategies for movement sequencing. However, unlike the conventional description, tongue-palate contact during propulsion was multidimensional with two distinct degrees of freedom in the front-to-back and the lateral-to-midline continua. Significant (Q<. 0 I) timing differences were found in that larger and thinner boluses were propelled faster than smaller and thicker ones, and dry swallows had longer full contact than water. For sequential swallowing during continuous drinking, the tongue used faster movement speed and overlapping gestures to meet the task demands, while propulsive contact pattern remained invariant. Thus, the change was not in motor strategies per se but in the timing coordination of the "drink" and "swallow" sequences. A 3-D model of oral lingual action for swallowing was proposed. Clinical implications were discussed. In sum, results of this study support the theory that swallowing motor control includes a peripheral mechanism capable of modulating centrally generated responses, and that the deglutitive motor program has both invariant and variant parameters

Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo