Florida doctors seeing Medicaid patients show broad interest in federal incentives for adopting electronic health records.

The Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009 aims to expand the use of electronic health records by offering financial incentives to physicians to fully adopt and implement them. We surveyed Florida physicians who deliver care to Medicaid participants to identify their interest in participating in the incentive program. More than 60 percent of all respondents expressed interest in applying for the incentives; of those already using electronic health record systems, 86 percent intend to apply for funding. This relatively high proportion of physicians creates the potential to reach the overall policy goals of the law. Among those not planning to seek incentives, common barriers--especially among nonusers of electronic health records--were "costs involved" (69 percent), "need more information about incentive program" (42 percent), and uncertainty about what system to purchase (42 percent). We suggest that these findings hold implications for the Regional Extension Centers working to help physicians achieve the federal meaningful-use criteria that are a condition of receiving the incentives. In particular, the centers should focus on providing physicians with information about costs of electronic health record systems.

Effects of acute ethanol exposure on regulatory mechanisms of Bcl-2-associated apoptosis promoter, bad, in neonatal rat cerebellum: differential effects during vulnerable and resistant developmental periods.

BACKGROUND: Prenatal alcohol exposure produces anatomical and behavioral abnormalities associated with fetal alcohol syndrome (FAS). Animal FAS models have demonstrated temporal windows of vulnerability in the developing cerebellum, with substantial ethanol (EtOH)-mediated apoptotic activation during these periods. In rodents, the cerebellum is most sensitive to EtOH on postnatal days 4 to 6 (P4 to P6). At slightly later ages (P7 and later), this region is less vulnerable to EtOH. The present study investigated EtOH effects on mechanisms related to activities of Bad, a proapoptotic member of the Bcl-2 gene family, to further characterize processes underlying these disparate EtOH sensitivities. In healthy cells, Bad is retained in the cytosol by association with 14-3-3, a primarily cytosolic protein. Bad promotes apoptosis by disassociating from 14-3-3 and sequestering Bcl-xL through heterodimerization. This dimerization prevents the neutralizing association of Bcl-xL with Bax, freeing Bax to perform in a prodeath manner. Caspase-dependent cleavage of Bad to a 15-kDa fragment increases its proapoptogenic capacity. METHODS: Two hours following EtOH exposure of P4 and P7 animals via inhalation, we determined how exposure affects intracellular localization and proteolytic cleavage of Bad and expression of cerebellar 14-3-3, using subcellular fractionation and Western blot techniques. Ethanol effects on interactions between Bad and 14-3-3 or Bcl-xL at the more vulnerable and less vulnerable ages were determined using an enzyme-linked immunosorbent assay-based technique to detect native protein-protein interactions. RESULTS: At P4, EtOH increased mitochondrial localization of Bad, expression of a 15-kDa fragment recognized by Bad antibody, and formation of Bad:Bcl-xL complexes. At that more vulnerable age, EtOH also decreased formation of Bad:14-3-3 complexes. At P7, EtOH increased Bad:14-3-3 complexes and reduced Bad:Bcl-xL complexes. Cytosolic 14-3-3 remained unchanged by EtOH at P4 and P7. CONCLUSIONS: Ethanol-induced alterations of Bad-related mechanisms at P4 favor a prodeath response. EtOH does not influence these same mechanisms in a manner that promotes cell death at P7. Divergent Bad-related responses at these 2 developmental ages likely contribute to their differential EtOH vulnerability.

Functional mechanisms of apoptosis-related proteins in neonatal rat cerebellum are differentially influenced by ethanol at postnatal days 4 and 7.

Exposure of the developing nervous system to ethanol (EtOH) produces neurological aberrations associated with fetal alcohol syndrome. During a well-defined period, cerebellar neurons are highly susceptible to EtOH-induced death, primarily through apoptosis. Neonatal rodent cerebellum is exquisitely sensitive to EtOH on postnatal days 4-6 (P4-6); however, at slightly later developmental ages (P7 and later), EtOH effects are minimal. We have previously shown that EtOH differentially influences expression of apoptosis-related proteins of the Bcl-2 survival-regulatory gene family in P4 and P7 cerebellum. In the present study, the effects of EtOH on multiple functional mechanisms of Bcl-2, Bcl-xL, and Bax were investigated to characterize further the processes underlying these disparate EtOH sensitivities. For these analyses, we addressed the following questions, by using P4 and P7 cerebellar tissue following in vivo exposure: 1) Are there differential patterns of expression of antiapoptotic Bcl-2 or proapoptotic Bax in EtOH-vulnerable Purkinje cells that could contribute to the different degrees of temporal EtOH vulnerability? 2) How does EtOH affect intracellular localization of apoptosis-related proteins? 3) Does cleavage of Bax contribute to EtOH sensitivity? 4) Does EtOH differentially modulate cerebellar protein-protein interactions of Bcl-2, Bcl-xL, and Bax at the vulnerable vs. the resistant ages? Overall, we show that, at P4, the EtOH-mediated effects on Bcl-2, Bcl-xL, and Bax favor a prodeath response, whereas most of the intracellular responses to EtOH exposure at P7 promote survival. Such differential responsiveness likely plays a major role in the disparate ethanol vulnerability at these two postnatal ages.

Mitochondrially targeted vitamin E and vitamin E mitigate ethanol-mediated effects on cerebellar granule cell antioxidant defense systems.

Ethanol (EtOH) disrupts the structure and function of the developing nervous system, sometimes leading to birth defects associated with fetal alcohol syndrome (FAS). Animal FAS models indicate that cellular membrane peroxidation, intracellular oxidant accumulation, and suppression of endogenous antioxidant enzymes contribute to the toxic effects of EtOH. Mitochondrially targeted vitamin E (MitoVit E), a chemically engineered form of vitamin E (VE) designed to accumulate in the mitochondria, has been shown to inhibit intracellular oxidant accumulation and cell death more effectively than VE. In previous investigations, we have shown that, in vivo, VE reduces neuronal death in the developing cerebellum of EtOH-exposed animals, and, in vitro, VE prevents apoptotic and necrotic death of EtOH-exposed cerebellar granule cells (CGCs). The present investigation shows that, in a FAS CGC model, 1 nM MitoVit E renders significant neuroprotection against EtOH concentrations as high as 1600 mg/dL. The present study also demonstrates that, in this same model, MitoVit E mitigates EtOH-induced accumulation of intracellular oxidants and counteracts suppression of glutathione peroxidase/glutathione reductase (GSH-Px/GSSG-R) functions, protein expression of gamma-glutamylcysteine synthetase (gamma-GCS), and total cellular glutathione (GSH) levels. In the presence and absence of EtOH, VE amplifies the protein expression levels of gamma-GCS, an enzyme that performs the rate-limiting step for GSH synthesis, and total GSH levels. These results suggest that MitoVit E and VE ameliorate EtOH toxicity through non-oxidant mechanisms-modulations of endogenous cellular proteins-and antioxidant means.

Ethanol-induced reduction of neurotrophin secretion in neonatal rat cerebellar granule cells is mitigated by vitamin E.

Ethanol exposure during nervous system development produces a range of abnormalities, and in humans may lead to the fetal alcohol syndrome. Among the mechanisms hypothesized to play roles in ethanol neurotoxicity are altered expression of supportive neurotrophic factors (NTFs), and cellular disturbances in oxidative processes. In this study, ethanol effects on secretion of two NTFs, brain-derived neurotrophic factor, and neurotrophin-3 were analyzed in neonatal rat cerebellar granule cells, and the potential of the antioxidant vitamin E to modulate ethanol effects was investigated. Ethanol exposure in these preparations reduced NTF secretion, but vitamin E appreciably ameliorated the ethanol effects. Possible mechanisms underlying both the ethanol effects on NTF secretion, and the protection of this antioxidant are considered.

Protective mechanisms of pycnogenol in ethanol-insulted cerebellar granule cells.

Pycnogenol (PYC), a patented combination of bioflavonoids extracted from the bark of French maritime pine (Pinus maritima), inhibits apoptosis and necrosis of developing neurons exposed acutely to ethanol (EtOH). The present study shows that the protective mechanisms of PYC in EtOH-exposed postnatal day 9 cerebellar granule cells (P9 CGCs) include (1) reduction of reactive oxygen species (ROS) production; (2) counteraction of suppressed copper/zinc superoxide dismutase (Cu/Zn SOD) and glutathione peroxidase/reductase (GSH-Px/GSSG-R) system activities; (3) upregulation of Cu/Zn SOD protein expression; (4) mitigation of the EtOH-mediated exacerbation of catalase (CAT) activity; and, (5) specific binding and inhibition of active caspase-3. These results indicate that the mechanisms by which PYC antagonizes EtOH-induced oxidative stress include oxidant scavenging and modulation of endogenous, cellular proteins. Using findings from the present and previous studies, a model delineating the mechanisms of EtOH effects on the system of antioxidant enzymes in developing CGCs is presented.

Pycnogenol and vitamin E inhibit ethanol-induced apoptosis in rat cerebellar granule cells.

Pycnogenol (PYC), a patented combination of bioflavonoids extracted from the bark of French maritime pine (Pinus maritima), scavenges free radicals and promotes cellular health. The protective capacity of PYC against ethanol toxicity of neurons has not previously been explored. The present study demonstrates that in postnatal day 9 (P9) rat cerebellar granule cells the antioxidants vitamin E (VE) and PYC (1) dose dependently block cell death following 400, 800, and 1600 mg/dL ethanol exposure (2) inhibit the ethanol-induced activation of caspase-3 in the same model system; and (3) reduce neuronal membrane disruption as assayed by phosphatidylserine translocation to the cell surface. These results suggest that both PYC and VE have the potential to act as therapeutic agents, antagonizing the induction of neuronal cell death by ethanol exposure.

Vitamin E amelioration of ethanol neurotoxicity involves modulation of apoptotis-related protein levels in neonatal rat cerebellar granule cells.

Developmental ethanol exposure leads to a variety of abnormalities in the central nervous system (CNS). Mechanisms proposed as underlying these effects include alterations of protective antioxidant support, increased generation of harmful free radicals, and altered expression of apoptosis-related proteins. In prior studies, exogenous antioxidant application has been found to reduce ethanol neurotoxicity, but the mechanisms by which this protection is afforded have not been defined. This study was designed to investigate the interactions between ethanol and the antioxidant vitamin E (alpha-tocopherol), with respect to neuronal survival and levels of proteins related to the Bcl-2 survival-regulatory gene family. Neonatal rat cerebellar granule cell cultures were used as a model system. It was found that ethanol significantly impaired neuronal survival in these preparations, and that survival in the presence of ethanol was enhanced by inclusion of vitamin E in the culture medium. This elevated survival was paralleled by increased levels of anti-apoptotic proteins (e.g., Bcl-2, Bcl-xl, activated Akt kinase), and concurrent downregulation of pro-apoptotic proteins (e.g., Bcl-xs). These results suggest that such alterations may represent an important mechanism whereby antioxidants protect against the neurotoxic effects of ethanol in the developing CNS. The possible manner by which these changes are effected are considered.