Can You Keep a Secret--You May Discover the Answer Is Yes under Missouri\u27s Privilege for Trade Secrets

This Note examines which factors give rise to classification of information, patterns, formulas and the like as trade secrets. Missouri\u27s legislature, in its Uniform Trade Secrets Act, has offered a noncomprehensive definition of trade secret. \u27 While this and other proffered definitions provide some guidance, attempting to define any term of art cannot be done in absolute measures

Spatial Localization and Quantitation of Androgens in Mouse Testis by Mass Spectrometry Imaging

Androgens are essential for male development and reproductive function. They are transported to their site of action as blood-borne endocrine hormones but can also be produced within tissues to act in intracrine and paracrine fashions. Because of this, circulating concentrations may not accurately reflect the androgenic influence within specific tissue microenvironments. Mass spectrometry imaging permits regional analysis of small molecular species directly from tissue surfaces. However, due to poor ionization and localized ion suppression, steroid hormones are difficult to detect. Here, derivatization with Girard T reagent was used to charge-tag testosterone and 5α-dihydrotestosterone allowing direct detection of these steroids in mouse testes, in both basal and maximally stimulated states, and in rat prostate. Limits of detection were ∼0.1 pg for testosterone. Exemplary detection of endogenous steroids was achieved by matrix-assisted laser desorption ionization and either Fourier transform ion cyclotron resonance detection (at 150 μm spatial resolution) or quadrupole-time-of-flight detection (at 50 μm spatial resolution). Structural confirmation was achieved by collision induced fragmentation following liquid extraction surface analysis and electrospray ionization. This application broadens the scope for derivatization strategies on tissue surfaces to elucidate local endocrine signaling in health and disease

Relative adrenal insufficiency in mice deficient in 5α-reductase 1

Patients with critical illness or hepatic failure exhibit impaired cortisol responses to ACTH, a phenomenon known as ‘relative adrenal insufficiency’. A putative mechanism is that elevated bile acids inhibit inactivation of cortisol in liver by 5α-reductases type 1 and type 2 and 5β-reductase, resulting in compensatory downregulation of the hypothalamic–pituitary–adrenal axis and adrenocortical atrophy. To test the hypothesis that impaired glucocorticoid clearance can cause relative adrenal insufficiency, we investigated the consequences of 5α-reductase type 1 deficiency in mice. In adrenalectomised male mice with targeted disruption of 5α-reductase type 1, clearance of corticosterone was lower after acute or chronic (eightfold, P<0.05) administration, compared with WT control mice. In intact 5α-reductase-deficient male mice, although resting plasma corticosterone levels were maintained, corticosterone responses were impaired after ACTH administration (26% lower, P<0.05), handling stress (2.5-fold lower, P<0.05) and restraint stress (43% lower, P<0.05) compared with WT mice. mRNA levels of Nr3c1 (glucocorticoid receptor), Crh and Avp in pituitary or hypothalamus were altered, consistent with enhanced negative feedback. These findings confirm that impaired peripheral clearance of glucocorticoids can cause ‘relative adrenal insufficiency’ in mice, an observation with important implications for patients with critical illness or hepatic failure, and for patients receiving 5α-reductase inhibitors for prostatic disease

Performance characteristics of upper airway critical collapsing pressure measurements during sleep

Objective: The critical pressure (PCRIT), a measurement of upper airway collapsibility, is a determinant of the severity of upper airway obstruction during sleep. We examined the performance characteristics of the passive and active PCRIT by examining both within-night and between-night variability in the measurements. Methods: We studied 54 sleep apnea patients (39 men, 15 women) and 34 normal subjects (20 men, 14 women) on either 1 or 2 nights during sleep. The PCRIT was measured during relative hypotonia ( passive state) or during periods of sustained upper airway obstruction used to recruit upper airway neuromuscular responses ( active state) within- and between-nights. In a subgroup of 10 normal subjects, we performed repeated measurements during hypnotic-induced sleep. Bland-Altman analyses were used to determine the within-night and between-night reliability of the PCRIT measurements. Results: There were no significant within-night or between-night differences for the mean passive PCRIT. The active PCRIT was ∼1 cm H 2O more collapsible on the second night than on the first night. The limits of agreement, which bound the passive and active PCRIT, was ∼ ± 3 cm H2O and was reduced to ∼ ± 1 cm H 2O for the passive PCRIT with hypnotic-induced sleep. Conclusion: Passive and active PCRIT measurements are reasonably reliable within and between nights. An approximately 3 cm H2O change in passive or active PCRIT appears to represent the minimally significant change in PCRIT necessary to assess the effect of an intervention (e.g., positional therapy, surgical interventions, oral appliance effects, and pharmacotherapy) on upper airway mechanical loads or neuromuscular responses

Performance Characteristics of Upper Airway Critical Collapsing Pressure Measurements during Sleep

Objective: The critical pressure (PCRIT), a measurement of upper airway collapsibility, is a determinant of the severity of upper airway obstruction during sleep. We examined the performance characteristics of the passive and active PCRIT by examining both within-night and between-night variability in the measurements. Methods: We studied 54 sleep apnea patients (39 men, 15 women) and 34 normal subjects (20 men, 14 women) on either 1 or 2 nights during sleep. The PCRIT was measured during relative hypotonia ( passive state) or during periods of sustained upper airway obstruction used to recruit upper airway neuromuscular responses ( active state) within- and between-nights. In a subgroup of 10 normal subjects, we performed repeated measurements during hypnotic-induced sleep. Bland-Altman analyses were used to determine the within-night and between-night reliability of the PCRIT measurements. Results: There were no significant within-night or between-night differences for the mean passive PCRIT. The active PCRIT was ∼1 cm H 2O more collapsible on the second night than on the first night. The limits of agreement, which bound the passive and active PCRIT, was ∼ ± 3 cm H2O and was reduced to ∼ ± 1 cm H 2O for the passive PCRIT with hypnotic-induced sleep. Conclusion: Passive and active PCRIT measurements are reasonably reliable within and between nights. An approximately 3 cm H2O change in passive or active PCRIT appears to represent the minimally significant change in PCRIT necessary to assess the effect of an intervention (e.g., positional therapy, surgical interventions, oral appliance effects, and pharmacotherapy) on upper airway mechanical loads or neuromuscular responses

Contribution of male sex, age, and obesity to mechanical instability of the upper airway during sleep

Male sex, obesity, and age are risk factors for obstructive sleep apnea, although the mechanisms by which these factors increase sleep apnea susceptibility are not entirely understood. This study examined the interrelationships between sleep apnea risk factors, upper airway mechanics, and sleep apnea susceptibility. In 164 (86 men, 78 women) participants with and without sleep apnea, upper airway pressure-flow relationships were characterized to determine their mechanical properties [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] during non-rapid eye movement sleep. In multiple linear regression analyses, the effects of body mass index and age on passive Pcrit were determined in each sex. A subset of men and women matched by body mass index, age, and disease severity was used to determine the sex effect on passive Pcrit . The passive Pcrit was 1.9 cmH 2 O [95% confidence interval (CI): 0.1-3.6 cmH 2 O] lower in women than men after matching for body mass index, age, and disease severity. The relationship between passive Pcrit and sleep apnea status and severity was examined. Sleep apnea was largely absent in those individuals with a passive Pcrit less than -5 cmH 2 O and increased markedly in severity when passive Pcrit rose above -5 cmH 2 O. Passive Pcrit had a predictive power of 0.73 (95% CI: 0.65-0.82) in predicting sleep apnea status. Upper airway mechanics are differentially controlled by sex, obesity, and age, and partly mediate the relationship between these sleep apnea risk factors and obstructive sleep apnea