Correction to: Lung cancer screening: an emerging cancer control issue presents opportunities for an awareness campaign in rural Michigan.

In the original publication of the article, the co-author name (Antoinette Percy-Laurry) was misspelled during the publication process. The coauthor name has been corrected in this correction.

Lung cancer screening: an emerging cancer control issue presents opportunities for an awareness campaign in rural Michigan.

Lung cancer is the leading cause of cancer deaths in the United States representing about 25% of all cancer deaths. The risk from smoking has increased over time with racial/ethnic minorities and disadvantaged populations having higher smoking rates and experiencing greater burden of lung cancer compared to other populations. Rural populations, in particular, experience higher rates of tobacco usage associated with increased incidence of lung cancer. National efforts to identify lung cancer in its early stage would greatly benefit high-risk populations, consequently reducing advanced cancers and potentially decreasing smoking rates. In 2013, lung cancer screening with low-dose computed tomography was recommended by the US Preventive Services Task Force for early detection of lung cancer. These guidelines were developed after the results of the National Lung Screening Trial. The National Lung Screening Trial study showed a 20% reduction in deaths of participants who were current or former heavy smokers who were screened with low-dose computed tomography versus those screened by chest X-ray. In response to this evidence and using state lung cancer burden data and local smoking rates as a guide, Michigan implemented a lung cancer screening awareness campaign in the rural northern, lower peninsula. Awareness of lung cancer screening was increased through the use of a variety of media including gas station/convenience store small media, digital media, radio broadcast media, and the use and marketing of a website that provided lung cancer screening information and resources.

Notch-Mediated Epigenetic Regulation of Voltage-Gated Potassium Currents.

RATIONALE: Ventricular arrhythmias often arise from the Purkinje-myocyte junction and are a leading cause of sudden cardiac death. Notch activation reprograms cardiac myocytes to an induced Purkinje-like state characterized by prolonged action potential duration and expression of Purkinje-enriched genes. OBJECTIVE: To understand the mechanism by which canonical Notch signaling causes action potential prolongation. METHODS AND RESULTS: We find that endogenous Purkinje cells have reduced peak K+ current, Ito, and IK,slow when compared with ventricular myocytes. Consistent with partial reprogramming toward a Purkinje-like phenotype, Notch activation decreases peak outward K+ current density, as well as the outward K+ current components Ito,f and IK,slow. Gene expression studies in Notch-activated ventricles demonstrate upregulation of Purkinje-enriched genes Contactin-2 and Scn5a and downregulation of K+ channel subunit genes that contribute to Ito,f and IK,slow. In contrast, inactivation of Notch signaling results in increased cell size commensurate with increased K+ current amplitudes and mimics physiological hypertrophy. Notch-induced changes in K+ current density are regulated at least in part via transcriptional changes. Chromatin immunoprecipitation demonstrates dynamic RBP-J (recombination signal binding protein for immunoglobulin kappa J region) binding and loss of active histone marks on K+ channel subunit promoters with Notch activation, and similar transcriptional and epigenetic changes occur in a heart failure model. Interestingly, there is a differential response in Notch target gene expression and cellular electrophysiology in left versus right ventricular cardiac myocytes. CONCLUSIONS: In summary, these findings demonstrate a novel mechanism for regulation of voltage-gated potassium currents in the setting of cardiac pathology and may provide a novel target for arrhythmia drug design.

Localized prostate cancer treatment decision-making information online: improving its effectiveness and dissemination for nonprofit and government-supported organizations.

The current study reports findings from evaluation research conducted to identify how online prostate cancer treatment decision-making information can be both improved and more effectively disseminated to those who need it most. A multi-method, multi-target approach was used and guided by McGuire's Communication Matrix Model. Focus groups (n = 31) with prostate cancer patients and their family members, and in-depth interviews with physicians (n = 8), helped inform a web survey (n = 89). Results indicated that physicians remain a key information source for medical advice and the Internet is a primary channel used to help make informed prostate cancer treatment decisions. Participants reported a need for more accessible information related to treatment options and treatment side effects. Additionally, physicians indicated that the best way for agencies to reach them with new information to deliver to patients is by contacting them directly and meeting with them one-on-one. Advice for organizations to improve their current prostate cancer web offerings and further ways to improve information dissemination are discussed.

Differential Expression and Remodeling of Transient Outward Potassium Currents in Human Left Ventricles.

BACKGROUND: Myocardial, transient, outward currents, Ito, have been shown to play pivotal roles in action potential (AP) repolarization and remodeling in animal models. The properties and contribution of Ito to left ventricular (LV) repolarization in the human heart, however, are poorly defined. METHODS AND RESULTS: Whole-cell, voltage-clamp recordings, acquired at physiological (35°C to 37°C) temperatures, from myocytes isolated from the LV of nonfailing human hearts identified 2 distinct transient currents, Ito,fast (Ito,f) and Ito,slow (Ito,s), with significantly (P<0.0001) different rates of recovery from inactivation and pharmacological sensitives: Ito,f recovers in ≈10 ms, 100× faster than Ito,s, and is selectively blocked by the Kv4 channel toxin, SNX-482. Current-clamp experiments revealed regional differences in AP waveforms, notably a phase 1 notch in LV subepicardial myocytes. Dynamic clamp-mediated addition/removal of modeled human ventricular Ito,f, resulted in hyperpolarization or depolarization, respectively, of the notch potential, whereas slowing the rate of Ito,f inactivation resulted in AP collapse. AP-clamp experiments demonstrated that changes in notch potentials modified the time course and amplitudes of voltage-gated Ca2+ currents, ICa. In failing LV subepicardial myocytes, Ito,f was reduced and Ito,s was increased, notch and plateau potentials were depolarized (P<0.0001) and AP durations were prolonged (P<0.001). CONCLUSIONS: Ito,f and Ito,s are differentially expressed in nonfailing human LV, contributing to regional heterogeneities in AP waveforms. Ito,f regulates notch and plateau potentials and modulates the time course and amplitude of ICa. Slowing Ito,f inactivation results in dramatic AP shortening. Remodeling of Ito,f in failing human LV subepicardial myocytes attenuates transmural differences in AP waveforms.

Malingering in toxic exposure: classification accuracy of reliable digit span and WAIS-III Digit Span scaled scores.

This study examined the sensitivity and false-positive error rate of reliable digit span (RDS) and the WAIS-III Digit Span (DS) scaled score in persons alleging toxic exposure and determined whether error rates differed from published rates in traumatic brain injury (TBI) and chronic pain (CP). Data were obtained from the files of 123 persons referred for neuropsychological evaluation related to alleged exposure to environmental and industrial substances. Malingering status was determined using the criteria of Slick, Sherman, and Iverson (1999). The sensitivity and specificity of RDS and DS in toxic exposure are consistent with those observed in TBI and CP. These findings support the use of these malingering indicators in cases of alleged toxic exposure and suggest that the classification accuracy data of indicators derived from studies of TBI patients may also be validly applied to cases of alleged toxic exposure.

Modulation of BK channels contributes to activity-dependent increase of excitability through MTORC1 activity in CA1 pyramidal cells of mouse hippocampus.

Memory acquisition and synaptic plasticity are accompanied by changes in the intrinsic excitability of CA1 pyramidal neurons. These activity-dependent changes in excitability are mediated by modulation of intrinsic currents which alters the responsiveness of the cell to synaptic inputs. The afterhyperpolarization (AHP), a major contributor to the regulation of neuronal excitability, is reduced in animals that have acquired several types of hippocampus-dependent memory tasks and also following synaptic potentiation by high frequency stimulation. BK channels underlie the fast AHP and contribute to spike repolarization, and this AHP is reduced in animals that successfully acquired trace-eyeblink conditioning. This suggests that BK channel function is activity-dependent, but the mechanisms are unknown. In this study, we found that blockade of BK channels with paxilline (10 µM) decreased I AHP amplitude and increased spike half-width and instantaneous frequency in response to a +100 pA depolarization. In addition, induction of long term potentiation (LTP) by theta burst stimulation (TBS) in CA1 pyramidal neurons reduced BK channel's contribution to I AHP, spike repolarization, and instantaneous frequency. This result indicates that BK channel activity is decreased following synaptic potentiation. Interestingly, blockade of mammalian target of rapamycin (MTORC1) with rapamycin (400 nM) following synaptic potentiation restored BK channel function, suggesting a role for protein translation in signaling events which decreased postsynaptic BK channel activity following synaptic potentiation.