Access to care barriers for patients with Bipolar disorder in the United States.

BACKGROUND: The five major comorbidities associated with Bipolar Disorder (BPD) include anxiety disorder, substance abuse, attention deficit hyperactivity disorder, personality disorder, and other medical conditions. These conditions are extremely prevalent among patients with BPD. Additionally, the medications used to treat this disorder can cause severe weight gain, which leads to cardiovascular disease, type 2 diabetes, and other endocrine disorders. PURPOSE: The purpose of this paper is to inform the medical community and health policymakers of the causes and comorbidities associated with BPD; stigma, acceptance of insurance, shortage of providers and costs as barriers to access care; and the collaborative care model and policy-based solutions to improve the access to high quality care and the quality of life of people living with bipolar disorder. RESULTS: Recent policy developments that address mental health in the United States, such as, the Mental Health Parity and Addiction Equity Act (MHPAEA) and the Helping Families in Mental Health Crisis Act are opportunities to improve access to care. Though not specifically targeting BPD, collaborative programs and mental health policies can start monitoring the comorbidities associated with BPD. By focusing on prevention and collaborative care, providers can slow the acceleration of symptoms and allow for quicker channels of treatment for comorbidities.

Is obesity a risk factor for readmission after acute myocardial infarction?

INTRODUCTION AND OBJECTIVES: Hospital readmissions are a major concern in terms of both cost and quality of care. The purpose of this study was to determine which patients were more likely to experience hospital readmissions after acute myocardial infarction in order to help develop more targeted programs and policies. PATIENTS AND MATERIALS AND METHODS: The 2014 Nationwide Readmissions Database was used to calculate the national readmission rate by patient characteristics. All U.S. patients who presented to the hospital with acute myocardial infarction in 2014 and incurred a readmission were included in this analysis. The main outcome of interest was the rate of readmission by obesity. Obesity was measured using the comorbidity indicator found in the dataset. National secondary data of a sample of U.S. hospital discharges was used to measure hospital readmission rates. Bivariate analysis and logistic regression were used to determine if a significant relationship existed between readmissions and the patient characteristics. For this purpose odds ratio (OR) and 95% confidence interval has been calculated. RESULTS: There were 11.66% hospital readmissions in the database. Non-obese adults were 21% less likely to be readmitted than obese adults. Non-obese patients were 21.2% less likely to be readmitted than obese patients (OR 0.788, CI 0.751-0.827, p-value <.0001). Obese patients with no insurance had significantly higher readmissions compared to obese Medicare patients. CONCLUSIONS: The Hospital Readmissions Reduction Program has been effective at reducing hospital readmissions. However, greater focus needs to be placed on reducing hospital readmissions for patients with chronic conditions, especially obesity.

Non-Arrhenius ionic conductivities in glasses due to a distribution of activation energies.

Previously observed non-Arrhenius behavior in fast ion conducting glasses [J. Kincs and S. W. Martin, Phys. Rev. Lett. 76, 70 (1996)] occurs at temperatures near the glass transition temperature, T(g), and is attributed to changes in the ion mobility due to ion trapping mechanisms that diminish the conductivity and result in a decreasing conductivity with increasing temperature. It is intuitive that disorder in glass will also result in a distribution of the activation energies (DAE) for ion conduction, which should increase the conductivity with increasing temperature, yet this has not been identified in the literature. In this Letter, a series of high precision ionic conductivity measurements are reported for 0.5Na(2)S + 0.5[xGeS(2) + (1-x)PS(5/2)] glasses with compositions ranging from 0 ≤ x ≤ 1. The impact of the cation site disorder on the activation energy is identified and explained using a DAE model. The absence of the non-Arrhenius behavior in other glasses is explained and it is predicted which glasses are expected to accentuate the DAE effect on the ionic conductivity.

Nitric oxide production by rat bronchoalveolar macrophages or polymorphonuclear leukocytes following intratracheal instillation of lipopolysaccharide or silica.

Exposure of the lung to lipopolysaccharide (LPS) or silica results in an activation of alveolar macrophages (AMs), recruitment of polymorphonuclear leukocytes (PMNs) into bronchoalveolar spaces, and the production of free radicals. Nitric oxide (NO) is one of the free radicals generated by bronchoalveolar lavage (BAL) cell populations following either LPS or silica exposure. The purpose of the present study was to assess the relative contributions of AMs and PMNs to the amounts of NO produced by BAL cells following intratracheal (IT) instillation of either LPS or silica. Male Sprague Dawley rats (265-340 g body wt.) were given LPS (10 mg/100 g body wt.) or silica (5 mg/100 g body wt.). BAL cells were harvested 18-24 h post-IT and enriched for AMs or PMNs using density gradient centrifugation. Media levels of nitrate and nitrite (NOx; the stable decomposition products of NO) were then measured 18 h after ex vivo culture of these cells. Following IT exposure to either LPS or silica, BAL cell populations were approximately 20% AMs and approximately 80% PMNs. After density gradient centrifugation of BAL cells from LPS- or silica-treated rats, cell fractions were obtained which were relatively enriched for AMs (approximately 60%) or PMNs (approximately 90%). The amounts of NOx produced by the AM-enriched fractions from LPS- or silica-treated rats were approximately 2-4-fold greater than that produced by the PMN-enriched fractions. Estimations of the relative contribution of AMs or PMNs to the NOx produced indicated that: (i) following LPS treatment, 75%-89% of the NOx was derived from AMs and 11%-25% from PMNs; and (ii) following silica treatment, 76%-100% of the NOx was derived from AMs and 0-24% from PMNs. Immunohistochemistry for inducible NO synthase on lung tissue sections supported these findings. We conclude that AMs are the major source of the NO produced by BAL cells during acute pulmonary inflammatory responses to LPS or silica.

Cytokine and nitric oxide release by J774A.1 macrophages is not regulated by estradiol.

Estradiol is able to regulate the release of inflammatory mediators by macrophages; however, the presence, extent, and direction of this modulation varies with species, tissue of origin, and cell culture conditions. This study examines the effects of 17-beta-estradiol (E2) on the release of inflammatory mediators by the J774A.1 mouse macrophage cell line. For experiments, cells were plated in phenol red-free DMEM containing 5% charcoal-dextran stripped calf serum. Western analysis showed that J774A.1 cells contain the estrogen receptor alpha (ER alpha) protein. We found that physiological and pharmacological levels of E2 (10(-12) M-10(-6) M) have no effect on the release of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), or monocyte chemoattractant protein-1 (MCP-1). This suggests that J774A.1 cells grown under these culture conditions would be useful for the investigation of non-estrogen-dependent mechanisms by which certain endocrine disruptors may affect their targets in macrophages.

Transformation of Lotus japonicus using the herbicide resistance bar gene as a selectable marker.

Transgenic plants of the model legume Lotus japonicus were regenerated by hypocotyl transformation using a bar gene as a selectable marker. The bar encodes for Phosphinothricin Acetyl Transferase that detoxifies phosphinothricin (PPT), the active ingredient of herbicides such as Ignite (AgrEvo) and Basta (Hoechst). Transgenic L. japonicus plants resistant to PPT were positive upon PCR by bar gene-specific primers. In 5 out of 7 independent lines tested, PPT resistance segregated as a single dominant allele indicating a single T-DNA insertion into the plant genome. All regenerated plants were fertile and void of visible somaclonal abnormalities contrary to 14% infertility when antibiotic selectable markers were used. The lack of somaclonal variation, ease of PPT application and low cost of PPT makes this protocol an attractive alternative for the regeneration of transgenic L. japonicus. The production of PPT herbicide-resistant L. japonicus plants may have significant commercial applications in crop production.

Monovalent Cation Activation of Plant Pyruvate Dehydrogenase Kinase.

The pyruvate dehydrogenase kinase-catalyzed inactivation of the pyruvate dehydrogenase complex was studied using dialyzed, soluble proteins from mitochondria purified from green leaf tissue of Pisum sativum L. seedlings. At subsaturating ATP concentrations, K+ or NH4+, but not Na+, stimulated the pyruvate dehydrogenase kinase by lowering the Km(ATP). Micromolar concentrations of NH4+ were required to produce the same effect as millimolar concentrations of K+. This is apparent from the observations that the activation constant (Kact) for NH4+ was 0.1 mM, whereas the Kact(K+) was 0.7 mM. Maximal pyruvate dehydrogenase kinase velocities attained with NH4+ were higher than those with K+, and, therefore, NH4+ was able to stimulate PDH kinase further in the presence of saturating K+. This result supports our conclusion that photorespiratory NH4+ production in plant mitochondria may be involved in regulating the entry of carbon into the Krebs cycle by way of the pyruvate dehydrogenase complex.

Phosphorylation of Soybean (Glycine max L.) Nodule Phosphoenolpyruvate Carboxylase in Vitro Decreases Sensitivity to Inhibition by L-Malate.

Phosphoenolpyruvate carboxylase (PEPC) from soybean (Glycine max L.Merr.) nodules was purified 187-fold to a final specific activity of 56 units mg-1 of protein. Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) revealed one major polypeptide band, with a molecular mass of 110 kD, after the final purification step. Two-dimensional PAGE resolved four isoelectric forms of the purified enzyme. Antibodies raised against the purified enzyme immunoprecipitated PEPC activity from a desalted nodule extract. Two cross-reacting bands were obtained when protein immunoblots of crude nodule extracts subjected to SDS-PAGE were probed with the antiserum. One of these corresponded to the 110-kD subunit of PEPC, and the other had a molecular mass of about 60 kD. PEPC was shown to be activated in a time-dependent manner when desalted soybean nodule extracts were preincubated with Mg.ATP in vitro. Activation was observed when PEPC was assayed at pH 7 in the absence of glycerol but not at pH 8 in the presence of glycerol. When o.5 mM L-malate was included in the assay, activation was much more pronounced than without malate. Maximal activation was 30% in the absence of L-malate and 200% in its presence. The L-malate concentrations producing 50% inhibition of PEPC activity were o.35 and 1.24 mM, respectively, before and after preincubation with Mg.ATP. The antiserum against soybean nodule PEPC was used to immunoprecipitate PEPC from a desalted nodule extract that had been preincubated with Mg.[[gamma]-32P]ATP. The immunoprecipitate was then subjected to SDS-PAGE, followed by autoradiography. The autoradiograph revealed intense labeling of the 110-kD subunit of PEPC following preincubation with [[gamma]-32P]ATP. The data suggest that soybean nodule PEPC becomes phosphorylated by an endogenous protein kinase, resulting in decreased sensitivity of the enzyme to inhibition by L-malate in vitro. The results are discussed in relation to the proposed functions of PEPC in legume nodules.

Metabolite regulation of partially purified soybean nodule phosphoenolpyruvate carboxylase.

Phosphoenolpyruvate carboxylase (PEPC) was purified 40-fold from soybean (Glycine max L. Merr.) nodules to a specific activity of 5.2 units per milligram per protein and an estimated purity of 28%. Native and subunit molecular masses were determined to be 440 and 100 kilodaltons, respectively, indicating that the enzyme is a homotetramer. The response of enzyme activity to phosphoenolpyruvate (PEP) concentration and to various effectors was influenced by assay pH and glycerol addition to the assay. At pH 7 in the absence of glycerol, the K(m) (PEP) was about twofold greater than at pH 7 in the presence of glycerol or at pH 8. At pH 7 or pH 8 the K(m) (MgPEP) was found to be significantly lower than the respective K(m) (PEP) values. Glucose-6-phosphate, fructose-6-phosphate, glucose-1-phosphate, and dihydroxyacetone phosphate activated PEPC at pH 7 in the absence of glycerol, but had no effect under the other assay conditions. Malate, aspartate, glutamate, citrate, and 2-oxoglutarate were potent inhibitors of PEPC at pH 7 in the absence of glycerol, but their effectiveness was decreased by raising the pH to 8 and/or by adding glycerol. In contrast, 3-phosphoglycerate and 2-phosphoglycerate were less effective inhibitors at pH 7 in the absence of glycerol than under the other assay conditions. Inorganic phosphate (up to 20 millimolar) was an activator at pH 7 in the absence of glycerol but an inhibitor under the other assay conditions. The possible significance of metabolite regulation of PEPC is discussed in relation to the proposed functions of this enzyme in legume nodule metabolism.

Relationship between NH(4) Assimilation Rate and in Vivo Phosphoenolpyruvate Carboxylase Activity : Regulation of Anaplerotic Carbon Flow in the Green Alga Selenastrum minutum.

The rate of NH(4) (+) assimilation by N-limited Selenastrum minutum (Naeg.) Collins cells in the dark was set as an independent variable and the relationship between NH(4) (+) assimilation rate and in vivo activity of phosphoenolpyruvate carboxylase (PEPC) was determined. In vivo activity of PEPC was measured by following the incorporation of H(14)CO(-) (3) into acid stable products. A linear relationship of 0.3 moles C fixed via PEPC per mole N assimilated was observed. This value agrees extremely well with the PEPC requirement for the synthesis of the amino acids found in total cellular protein. Determinations of metabolite levels in vivo at different rates of N assimilation indicated that the known metabolite effectors of S. minutum PEPC in vitro (KA Schuller, WC Plaxton, DH Turpin, [1990] Plant Physiol 93: 1303-1311) are important regulators of this enzyme during N assimilation. As PEPC activity increased in response to increasing rates of N assimilation, there was a corresponding decline in the level of PEPC inhibitors (2-oxoglutarate, malate), an increase in the level of PEPC activators (glutamine, dihydroxyacetone phosphate), and an increase in the Gln/Glu ratio. Treatment of N-limited cells with azaserine caused an increase in the Gln/Glu ratio resulting in increased PEPC activity in the absence of N assimilation. We suggest glutamate and glutamine play a key role in regulating the anaplerotic function of PEPC in this C(3) organism.

Regulation of Phosphoenolpyruvate Carboxylase from the Green Alga Selenastrum minutum: Properties Associated with Replenishment of Tricarboxylic Acid Cycle Intermediates during Ammonium Assimilation.

Two isoforms of phosphoenolpyruvate carboxylase (PEPC) with very different regulatory properties were partially purified from the green alga Selenastrum minutum. They were designated PEPC(1) and PEPC(2). PEPC(1) showed sigmoidal kinetics with respect to phosphoenolpyruvate (PEP) whereas PEPC(2) exhibited a typical Michaelis-Menten response. The S(0.5)(PEP) of PEPC(1) was 2.23 millimolar. This was fourfold greater than the S(0.5)(PEP) of PEPC(2), which was 0.57 millimolar. PEPC(1) was activated more than fourfold by 2.0 millimolar glutamine and sixfold by 2.0 millimolar dihydroxyacetone phosphate (DHAP) at a subsaturating PEP concentration of 0.625 millimolar. In contrast, PEPC(2) showed only 8% and 52% activation by glutamine and DHAP, respectively. The effects of glutamine and DHAP were additive. PEPC(1) was more sensitive to inhibition by glutamate, 2-oxoglutarate, and aspartate than PEPC(2). Both isoforms were equally inhibited by malate. All of these metabolites affected only the S(0.5)(PEP) not the V(max). The regulatory properties of S. minutum PEPC in vitro are discussed in terms of (a) increased rates of dark carbon fixation (shown to be catalyzed predominantly by PEPC) and (b) changes in metabolite levels in vivo during enhanced NH(4+) assimilation. Finally, a model is proposed for the regulation of PEPC in vivo in relation to its role in replenishing tricarboxylic acid cycle intermediates consumed in NH(4+) assimilation.

Mechanism of pyruvate inhibition of plant pyruvate dehydrogenase kinase and synergism with ADP.

The effects of various metabolites on pyruvate dehydrogenase (PDH) kinase-catalyzed inactivation of the pyruvate dehydrogenase complex (PDC) were studied in extracts of mitochondria purified from green leaf tissue of Pisum sativum L. Pyruvate was an uncompetitive inhibitor of PDH kinase with respect to ATP whereas ADP was a competitive inhibitor. In the absence of pyruvate a fivefold excess of ADP over ATP was required to inhibit PDH kinase, however, in the presence of pyruvate much lower ADP concentrations were required. Inhibition of PDH kinase by pyruvate and ADP was synergistic and the addition of ADP changed pyruvate from an uncompetitive inhibitor to a noncompetitive inhibitor. This result indicates that pyruvate acts as a "dead-end" inhibitor, binding to the PDH kinase-ADP reaction intermediate. Evidence is also presented that inhibition by pyruvate in the presence of thiamine pyrophosphate is due to the formation of hydroxyethyl thiamine pyrophosphate. The results are discussed in terms of the regulation of PDC activity by pyruvate and ADP during periods of increased demand for carbon skeleton biosynthesis by way of the tricarboxylic acid (TCA) cycle despite constraints imposed on TCA cycle flux by a high ATP/ADP ratio.

Regulation of pea mitochondrial pyruvate dehydrogenase complex : does photorespiratory ammonium influence mitochondrial carbon metabolism?

Inactivation of the pyruvate dehydrogenase complex catalyzed by pyruvate dehydrogenase kinase was studied using intact mitochondria purified from green leaf tissue of pea (Pisum sativum L.) and dialyzed mitochondrial extracts. Thiamine pyrophosphate was inhibitory in dialyzed extracts but not in intact mitochondria, except in the presence of high concentrations of Na(+). NH(4) (+), at concentrations as low as 20 micromolar, markedly stimulated inactivation in dialyzed extracts. K(+) in the range 1 to 10 millimolar also enhanced inactivation. In contrast, Na(+) was without affect at lower concentrations but was inhibitory at 10 to 100 millimolar levels. The effect of NH(4) (+) is discussed in relation to a possible regulatory interaction between photorespiratory NH(4) (+) production and the entry of carbon into the tricarboxylic acid cycle by way of the pyruvate dehydrogenase complex.

Enzymes of ammonia assimilation and ureide biosynthesis in soybean nodules: effect of nitrate.

The effect of nitrate on N(2) fixation and the assimilation of fixed N(2) in legume nodules was investigated by supplying nitrate to well established soybean (Glycine max L. Merr. cv Bragg)-Rhizobium japonicum (strain 3I1b110) symbioses. Three different techniques, acetylene reduction, (15)N(2) fixation and relative abundance of ureides ([ureides/(ureides + nitrate + alpha-amino nitrogen)] x 100) in xylem exudate, gave similar results for the effect of nitrate on N(2) fixation by nodulated roots. After 2 days of treatment with 10 millimolar nitrate, acetylene reduction by nodulated roots was inhibited by 48% but there was no effect on either acetylene reduction by isolated bacteroids or in vitro activity of nodule cytoplasmic glutamine synthetase, glutamine oxoglutarate aminotransferase, xanthine dehydrogenase, uricase, or allantoinase. After 7 days, acetylene reduction by isolated bacteroids was almost completely inhibited but, except for glutamine oxoglutarate aminotransferase, there was still no effect on the nodule cytoplasmic enzymes. It was concluded that, when nitrate is supplied to an established symbiosis, inhibition of nodulated root N(2) fixation precedes the loss of the potential of bacteroids to fix N(2). This in turn precedes the loss of the potential of nodules to assimilate fixed N(2).