PAK1 Protein Expression in the Auditory Cortex of Schizophrenia Subjects

Deficits in auditory processing are among the best documented endophenotypes in schizophrenia, possibly due to loss of excitatory synaptic connections. Dendritic spines, the principal post-synaptic target of excitatory projections, are reduced in schizophrenia. p21-activated kinase 1 (PAK1) regulates both the actin cytoskeleton and dendritic spine density, and is a downstream effector of both kalirin and CDC42, both of which have altered expression in schizophrenia. This study sought to determine if there is decreased auditory cortex PAK1 protein expression in schizophrenia through the use of quantitative western blots of 25 schizophrenia subjects and matched controls. There was no significant change in PAK1 level detected in the schizophrenia subjects in our cohort. PAK1 protein levels within subject pairs correlated positively with prior measures of total kalirin protein in the same pairs. PAK1 level also correlated with levels of a marker of dendritic spines, spinophilin. These latter two findings suggest that the lack of change in PAK1 level in schizophrenia is not due to limited sensitivity of our assay to detect meaningful differences in PAK1 protein expression. Future studies are needed to evaluate whether alterations in PAK1 phosphorylation states, or alterations in protein expression of other members of the PAK family, are present in schizophrenia

Evaluating Disparities Affecting Time from Emergency Department Door to Electrocardiogram in Chest Pain Patients

Introduction: For patients presenting to an emergency department with a chief complaint of chest pain, current American Heart Association guidelines recommend that time from emergency department arrival to completion of electrocardiogram be 10 minutes or less. The aim of this study is to evaluate if differences still exist amongst a diverse patient population presenting to a busy urban emergency department with a chief complaint of chest pain. Methods: This retrospective study looked at 3,419 patients who presented to the Emergency Department with any complaint of chest pain during the medical screening examination. Arrival time and time of first electrocardiogram along with age, gender, race, ethnicity and primary language were extracted from electronic health records. Results: For all patients, the mean time to electrocardiogram was 12.5 minutes (95% CI: 12.1-12.7) and 49.9% of all patients received an electrocardiogram within 10 minutes of arrival. Mean time for men was 11.6 minutes and for women 13.3 minutes (P<0.0001); in addition 54% of men and 44.4% of women had electrocardiogram done within 10 minutes of arrival (P<0.0001). No differences were found with regards to primary language, race or ethnicity of patients. Mean time to electrocardiogram for patients less than 40 years old was 14.6 minutes, which was significantly longer than patients equal or older than 40 years, who’s mean time was 11.9 minutes (p<0.0001). The effect of age was observed across gender, race, ethnicity and primary language spoken by the patients.  Conclusions: Patient presenting to the emergency department with chest pain are subject to several biases that potentially create health disparities. In this study we show that younger patients and women had a delay in time to electrocardiogram showing biases are still an issue

Increased expression of Kalirin-9 in the auditory cortex of schizophrenia subjects: Its role in dendritic pathology

Reductions in dendritic arbor length and complexity are among the most consistently replicated changes in neuronal structure in post mortem studies of cerebral cortical samples from subjects with schizophrenia, however, the underlying molecular mechanisms have not been identified. This study is the first to identify an alteration in a regulatory protein which is known to promote both dendritic length and arborization in developing neurons, Kalirin-9. We found Kalirin-9 expression to be paradoxically increased in schizophrenia. We followed up this observation by overexpressing Kalirin-9 in mature primary neuronal cultures, causing reduced dendritic length and complexity. Kalirin-9 overexpression represents a potential mechanism for dendritic changes seen in schizophrenia