Update on population-based preconception and prenatal cystic fibrosis carrier screening

Implementation of population-based cystic fibrosis (CF) carrier screening for all preconception and prenatal patients has encountered numerous challenges. Continuing education of the practitioner and patient is critical for ensuring the successful implementation of CF population-based carrier screening as well as other anticipated population-based molecular screening tests resulting from the completion of the Human Genome Project. To assist the practitioner, this article provides a brief review of cystic fibrosis genetics, the recommended screening guidelines and benefits of carrier screening, in addition to highlighting clinical dilemmas that have arisen since widespread CF carrier screening was initiated.     

Temperature-Acclimated Brown Adipose Tissue Modulates Insulin Sensitivity in Humans

In rodents, brown adipose tissue (BAT) regulates cold- and diet-induced thermogenesis (CIT; DIT). Whether BAT recruitment is reversible and how it impacts on energy metabolism have not been investigated in humans. We examined the effects of temperature acclimation on BAT, energy balance, and substrate metabolism in a prospective crossover study of 4-month duration, consisting of four consecutive blocks of 1-month overnight temperature acclimation (24°C [month 1] → 19°C [month 2] → 24°C [month 3] → 27°C [month 4]) of five healthy men in a temperature-controlled research facility. Sequential monthly acclimation modulated BAT reversibly, boosting and suppressing its abundance and activity in mild cold and warm conditions (P < 0.05), respectively, independent of seasonal fluctuations (P < 0.01). BAT acclimation did not alter CIT but was accompanied by DIT (P < 0.05) and postprandial insulin sensitivity enhancement (P < 0.05), evident only after cold acclimation. Circulating and adipose tissue, but not skeletal muscle, expression levels of leptin and adiponectin displayed reciprocal changes concordant with cold-acclimated insulin sensitization. These results suggest regulatory links between BAT thermal plasticity and glucose metabolism in humans, opening avenues to harnessing BAT for metabolic benefits.     

Further evidence of construct validity of standardized patient‐based performance examinations

The purpose of this study was to gather additional evidence pertinent to the construct validity of standardized patient‐based clinical performance examinations. Specifically, the study determined whether students who indicated they had previously read about, seen, or worked up a case on the examination performed differently on that case from those students who had not. Overall, it was found that students with previous reading or direct experiences with cases on the test tended to have higher case mean scores on those cases than those who had not. These results demonstrated that scores on standardized patient‐based performance examinations are sensitive to the examinees’ various learning experiences.     

Halothane Inhibits Contraction and Action Potential Duration to a Greater Extent in Subendocardial than Subepicardial Myocytes from the Rat Left Ventricle

Background : Halothane inhibits the 4-aminopyridine-sensitive transient outward K+ current (Ito), which in many species, including humans, plays an important role in determining action potential duration. As Ito is greater in the ventricular subepicardium than subendocardium, halothane may have differential effects on action potential duration and, therefore, contraction in cells isolated from these two regions.

Methods : Myocytes were isolated from the subendocardium and subepicardium of the rat left ventricle. Myocytes from each region were electrically stimulated at 1 Hz to measure contractions and action potentials and exposed to 0.6 mm halothane (approximately 2 x minimum alveolar concentration50 for the rat) for 1 min. The time from the peak of the action potential to repolarization at 0 and -50 mV was measured to assess the effects of halothane on action potential duration.

Results : Halothane inhibited contraction to a significantly (P = 0.002) greater extent in subendocardial myocytes than in subepicardial myocytes: the amplitude of contraction during control conditions was 3.6 +/- 0.4 [mu]m and 3.2 +/- 0.7 [mu]m in subendocardial and subepicardial cells, respectively, and this was reduced to 1.1 +/- 0.2 [mu]m (29 +/- 2% of control, P < 0.0001, n = 10) and 1.4 +/- 0.3 [mu]m (46 +/- 3% of control, P = 0.007, n = 7), respectively, after a 1-min exposure to 0.6 mm halothane. Control action potential duration (at -50 mV) was 67 +/- 10 and 28 +/- 4 ms in subendocardial and subepicardial myocytes, respectively, and these values were reduced to 39 +/- 6 ms (58 +/- 3% of control, P < 0.001) and 20 +/- 3 ms (73 +/- 5% of control, P = 0.009) by halothane, respectively.     

Association of Prehospital Step 1 Vital Sign Criteria and Vital Sign Decline with Increased Emergency Department and Hospital Death

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