Therapeutic Benefit and Gene Network Regulation by Combined Gene Transfer of Apelin,FGF2, and SERCA2a into Ischemic Heart

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High-resolution wrist-worn overnight oximetry has high positive predictive value for obstructive sleep apnea in a sleep study referral population

Background

Reducing the need for diagnostic sleep studies for obstructive sleep apnea (OSA) would reduce direct and opportunity costs while expediting time to treatment for this common and morbid disorder. We sought to determine if an established sleep apnea screening questionnaire (STOP-BANG) and wrist-worn overnight oximetry data could provide high positive predictive value for the presence of OSA.

Methods

We conducted a prospective observational study of consecutive unattended sleep study patients at a single facility. Patients were referred for sleep testing after chart review by a sleep physician. We assessed area under the receiver-operating characteristic curve (ROC AUC) and positive predictive value (PPV) of STOP-BANG score and oxygen desaturation index (ODI) for a respiratory disturbance index (RDI) ≥15/h.

Results

Among 234 test patients, 65 % had an RDI ≥15/h. STOP-BANG had poor ability to discriminate these patients (ROC AUC 0.62). ODI added significant diagnostic information to the STOP-BANG score, increasing the ROC AUC to 0.86. Having the ODI, the STOP-BANG score no longer contributed significant diagnostic information, and the ODI alone discriminated as well as the combination (ROC AUC 0.86). Forty nine percent had an ODI ≥7/h, which had PPV of 92 % (95 % confidence interval (CI), 86 to 96 %). In the validation sample of 1,196 consecutive patients, ODI?≥?7/h had a PPV of 97 % (95 % CI, 95 to 97 %).

Conclusions

Among patients with a high prevalence of OSA, high ODI is common and its presence has high PPV for OSA. These data suggest that overnight oximetry prior to sleep testing could significantly reduce the number of patients requiring sleep studies, thereby reducing costs and time to treatment.

     

Alternative Gnas gene products have opposite effects on glucose and lipid metabolism

Gnas is an imprinted gene with multiple gene products resulting from alternative splicing of different first exons onto a common exon 2. These products include stimulatory G protein alpha-subunit (G(s)alpha), the G protein required for receptor-stimulated cAMP production; extralarge G(s)alpha (XLalphas), a paternally expressed G(s)alpha isoform; and neuroendocrine-specific protein (NESP55), a maternally expressed chromogranin-like protein. G(s)alpha undergoes tissue-specific imprinting, being expressed primarily from the maternal allele in certain tissues. Heterozygous mutation of exon 2 on the maternal (E2m-/+) or paternal (E2+/p-) allele results in opposite effects on energy metabolism. E2m-/+ mice are obese and hypometabolic, whereas E2+/p- mice are lean and hypermetabolic. We now studied the effects of G(s)alpha deficiency without disrupting other Gnas gene products by deleting G(s)alpha exon 1 (E1). E1+/p- mice lacked the E2+/p- phenotype and developed obesity and insulin resistance. The lean, hypermetabolic, and insulin-sensitive E2+/p- phenotype appears to result from XLalphas deficiency, whereas loss of paternal-specific G(s)alpha expression in E1+/p- mice leads to an opposite metabolic phenotype. Thus, alternative Gnas gene products have opposing effects on glucose and lipid metabolism. Like E2m-/+ mice, E1m-/+ mice had s.c. edema at birth, presumably due to loss of maternal G(s)alpha expression. However, E1m-/+ mice differed from E2m-/+ mice in other respects, raising the possibility for the presence of other maternal-specific gene products. E1m-/+ mice had more severe obesity and insulin resistance and lower metabolic rate relative to E1+/p- mice. Differences between E1m-/+ and E1+/p- mice presumably result from differential effects on G(s)alpha expression in tissues where G(s)alpha is normally imprinted.