Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to altered dysbindin-1 gene expression

DTNBP1 (dystrobrevin binding protein 1) remains one of the top candidate genes in schizophrenia. Reduced expression of this gene and the protein it encodes, dysbindin-1, has been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia cases. It has not been established, however, if all dysbindin-1 isoforms are reduced in the DLPFC or if the reduction is associated with reduced DTNBP1 gene expression. Using Western blotting of whole-tissue lysates of the DLPFC with antibodies differentially sensitive to the three major isoforms of this protein (dysbindin-1A, -1B, and -1C), we found no significant differences between our schizophrenia cases and matched controls in dysbindin-1A or -1B, but did find a mean 46% reduction in dysbindin-1C in 71% of 28 case-control pairs (p = 0.022). This occurred in the absence of the one DTNBP1 risk haplotype for schizophrenia reported in the US and without alteration in levels of dysbindin-1C transcripts. Conversely, the absence of changes in the dysbindin-1A and -1B isoforms was accompanied by increased levels of their transcripts. We thus found no correspondence between alterations in dysbindin-1 gene and protein expression, the latter of which might be due to posttranslational modifications such as ubiquitination. Reduced DLPFC dysbindin-1C in schizophrenia probably occurs in PSDs, where we find dysbindin-1C to be heavily concentrated in the human brain. Given known postsynaptic effects of dysbindin-1 reductions in the rodent homolog of the prefrontal cortex, these findings suggest that reduced dysbindin-1C in the DLPFC may contribute to cognitive deficits of schizophrenia by promoting NMDA receptor hypofunction

Association Between Public Reporting of Outcomes With Procedural Management and Mortality for Patients With Acute Myocardial Infarction

AbstractBackgroundPublic reporting of procedural outcomes may create disincentives to provide percutaneous coronary intervention (PCI) for critically ill patients.ObjectivesThis study evaluated the association between public reporting with procedural management and outcomes among patients with acute myocardial infarction (AMI).MethodsUsing the Nationwide Inpatient Sample, we identified all patients with a primary diagnosis of AMI in states with public reporting (Massachusetts and New York) and regionally comparable states without public reporting (Connecticut, Maine, Maryland, New Hampshire, Rhode Island, and Vermont) between 2005 and 2011. Procedural management and in-hospital outcomes were stratified by public reporting.ResultsAmong 84,121 patients hospitalized with AMI, 57,629 (69%) underwent treatment in a public reporting state. After multivariate adjustment, percutaneous revascularization was performed less often in public reporting states than in nonreporting states (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.67 to 0.96), especially among older patients (OR: 0.75, 95% CI: 0.62 to 0.91), those with Medicare insurance (OR: 0.75, 95% CI: 0.62 to 0.91), and those presenting with ST-segment elevation myocardial infarction (OR: 0.63, 95% CI: 0.56 to 0.71) or concomitant cardiac arrest or cardiogenic shock (OR: 0.58, 95% CI: 0.47 to 0.70). Overall, patients with AMI in public reporting states had higher adjusted in-hospital mortality rates (OR: 1.21, 95% CI: 1.06 to 1.37) than those in nonreporting states. This was observed predominantly in patients who did not receive percutaneous revascularization in public reporting states (adjusted OR: 1.30, 95% CI: 1.13 to 1.50), whereas those undergoing the procedure had lower mortality (OR: 0.71, 95% CI: 0.62 to 0.83).ConclusionsPublic reporting is associated with reduced percutaneous revascularization and increased in-hospital mortality among patients with AMI, particularly among patients not selected for PCI

Association between diagnosis code expansion and changes in 30-day risk-adjusted outcomes for cardiovascular diseases

BACKGROUND In January 2011, Centers for Medicare and Medicaid Services expanded the number of inpatient diagnosis codes from 9 to 25, which may influence comorbidity counts and risk-adjusted outcome rates for studies spanning January 2011. This study examines the association between (1) limiting versus not limiting diagnosis codes after 2011, (2) using inpatient-only versus inpatient and outpatient data, and (3) using logistic regression versus the Centers for Medicare and Medicaid Services risk-standardized methodology and changes in risk-adjusted outcomes. METHODS AND RESULTS Using 100% Medicare inpatient and outpatient files between January 2009 and December 2013, we created 2 cohorts of fee-for-service beneficiaries aged ≥65 years. The acute myocardial infarction cohort and the heart failure cohort had 578 728 and 1 595 069 hospitalizations, respectively. We calculate comorbidities using (1) inpatient-only limited diagnoses, (2) inpatient-only unlimited diagnoses, (3) inpatient and outpatient limited diagnoses, and (4) inpatient and outpatient unlimited diagnoses. Across both cohorts

Serologic and Molecular Detection of Granulocytic Ethrlichiosis in Rhode Island

A new indirect fluorescent-antibody (IFA) assay with antigen produced in vitro in the human promyelocytic leukemia cell line HL60 was used to identify the first recognized case of human granulocytic ehrlichiosis in Rhode Island. This IFA assay was used to detect granulocytic ehrlichiae in white-footed mice and in a dog inhabiting the area surrounding the patient’s residence. Host-seeking Ixodes scapularis ticks found in the same habitat also were infected. I. scapularis ticks collected from other locations were fed on dogs and New Zealand White rabbits to assess the competency of these species as hosts of granulocytotropic Ehrlichia. Tick-induced infections of dogs were confirmed by serologic testing, tissue culture isolation, and PCR amplification, whereas several rabbits seroconverted but were PCR and culture negative. PCR amplification of the 16S rRNA gene and DNA sequencing of the PCR products or culture isolation was used to confirm granulocytic Ehrlichia infections in humans, dogs, white-footed mice, and ticks

Andreev Reflection and Spin Injection into s−s- and d−d-wave Superconductors

We study the effect of spin injection into $s-$ and $d-$wave superconductors, with an emphasis on the interplay between boundary and bulk spin transport properties. The quantities of interest include the amount of non-equilibrium magnetization ($m$), as well as the induced spin-dependent current ($I_s$) and boundary voltage ($V_s$). In general, the Andreev reflection makes each of the three quantities depend on a different combination of the boundary and bulk contributions. The situation simplifies either for half-metallic ferromagnets or in the strong barrier limit, where both $V_s$ and $m$ depend solely on the bulk spin transport/relaxation properties. The implications of our results for the on-going spin injection experiments in high $T_c$ cuprates are discussed.Comment: 4 pages, REVTEX, 1 figure included; typos correcte

Clinical Prediction Model Suitable for Assessing Hospital Quality for Patients Undergoing Carotid Endarterectomy

Background: Assessing hospital quality in the performance of carotid endarterectomy (CEA) requires appropriate risk adjustment across hospitals with varying case mixes. The aim of this study was to develop and validate a prediction model to assess the risk of in‐hospital stroke or death after CEA that could aid in the assessment of hospital quality. Methods and Results: Patients from National Cardiovascular Data Registry (NCDR)'s Carotid Artery Revascularization and Endarterectomy (CARE) Registry undergoing CEA without acute evolving stroke from 2005 to 2013 were included. In‐hospital stroke or death was modeled using hierarchical logistic regression with 20 candidate variables and accounting for hospital‐level clustering. Internal validation was achieved with bootstrapping; model discrimination and calibration were assessed. A total of 213 (1.7%) primary end point events occurred during 12 889 procedures. Independent predictors of stroke or death included age, prior peripheral artery disease, diabetes mellitus, prior coronary artery disease, having a symptomatic carotid lesion, having a contralateral carotid occlusion, or having New York Heart Association Class III or IV heart failure. The model was well calibrated and demonstrated moderate discriminative ability (c‐statistic 0.65). The NCDR CEA score was then developed to support simple, prospective risk quantification in the clinical setting. Conclusions: The NCDR CEA score, comprising 7 clinical variables, predicts in‐hospital stroke or death after CEA. This model can be used to estimate hospital risk‐adjusted outcomes for CEA and to assist with the assessment of hospital quality

Risk‐Treatment Paradox in the Selection of Transradial Access for Percutaneous Coronary Intervention

Background: Access site complications contribute to morbidity and mortality during percutaneous coronary intervention (PCI). Transradial arterial access significantly lowers the risk of access site complications compared to transfemoral arteriotomy. We sought to develop a prediction model for access site complications in patients undergoing PCI with femoral arteriotomy, and assess whether transradial access was selectively used in patients at high risk for complications. Methods and Results: We analyzed 17 509 patients who underwent PCI without circulatory support from 2008 to 2011 at 5 institutions. Transradial arterial access was used in 17.8% of patients. In those who underwent transfemoral access, 177 (1.2%) patients had access site complications. Using preprocedural clinical and demographic data, a prediction model for femoral arteriotomy complications was generated. The variables retained in the model included: elevated age (P<0.001), female gender (P<0.001), elevated troponin (P<0.001), decreased renal function or dialysis (P=0.002), emergent PCI (P=0.01), prior PCI (P=0.005), diabetes (P=0.008), and peripheral artery disease (P=0.003). The model showed moderate discrimination (optimism‐adjusted c‐statistic=0.72) and was internally validated via bootstrap resampling. Patients with higher predicted risk of complications via transfemoral access were less likely to receive transradial access (P<0.001). Similar results were seen in patients presenting with and without ST‐segment myocardial infarction and when adjusting for individual physician operator. Conclusions: We generated and validated a model for transfemoral access site complications during PCI. Paradoxically, patients most likely to develop access site complications from transfemoral access, and therefore benefit from transradial access, were the least likely to receive transradial access