Author Correction: Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death.

There was an error introduced into Figures 4, 5, and 7 during the proofing stage which has since been corrected.

Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death.

The mitogen-activated protein kinase (MAPK) pathway has been shown to be involved in both neurodevelopment and neurodegeneration. c-Jun N-terminal kinase (JNK), a MAPK important in retinal development and after optic nerve crush injury, is regulated by two upstream kinases: MKK4 and MKK7. The specific requirements of MKK4 and MKK7 in retinal development and retinal ganglion cell (RGC) death after axonal injury, however, are currently undefined.

Analysis of a practical surgical skills laboratory for nerve sparing radical prostatectomy.

Purpose: With the rapidly expanding anatomical and technical knowledge surrounding nervesparing radical prostatectomy (NSRP), anatomical and operative textbooks have failed to keep pace with the literature. A surgical skill laboratory (SSL) was designed to educate urology trainees on surgical anatomy and techniques for NSRP. The objective was to assess the validity of a SSL program.

Jnk2 deficiency increases the rate of glaucomatous neurodegeneration in ocular hypertensive DBA/2J mice.

The cJun N-terminal kinases (JNKs; JNK1, JNK2, and JNK3) promote degenerative processes after neuronal injury and in disease. JNK2 and JNK3 have been shown to promote retinal ganglion cell (RGC) death after optic nerve injury. In their absence, long-term survival of RGC somas is significantly increased after mechanical optic nerve injury.

Assessment of intrinsic and extrinsic signaling pathway in excitotoxic retinal ganglion cell death.

Excitotoxicity leads to the activation of a cytotoxic cascade that causes neuronal death. In the retina, retinal ganglion cells (RGCs) die after an excitotoxic insult. Multiple pathways have been proposed to contribute to RGC death after an excitotoxic insult, including TNF signaling, JNK activation, and ER stress.

Role of SARM1 and DR6 in retinal ganglion cell axonal and somal degeneration following axonal injury.

Optic neuropathies such as glaucoma are characterized by the degeneration of retinal ganglion cells (RGCs) and the irreversible loss of vision. In these diseases, focal axon injury triggers a propagating axon degeneration and, eventually, cell death. Previous work by us and others identified dual leucine zipper kinase (DLK) and JUN N-terminal kinase (JNK) as key mediators of somal cell death signaling in RGCs following axonal injury.

Together JUN and DDIT3 (CHOP) control retinal ganglion cell death after axonal injury.

Background: Optic nerve injury is an important pathological component in neurodegenerative diseases such as traumatic optic neuropathies and glaucoma. The molecular signaling pathway(s) critical for retinal ganglion cell (RGC) death after axonal insult, however, is/are not fully defined. RGC death after axonal injury is known to occur by BAX-dependent apoptosis.

KLF9 and JNK3 Interact to Suppress Axon Regeneration in the Adult CNS.

Neurons in the adult mammalian CNS decrease in intrinsic axon growth capacity during development in concert with changes in Krüppel-like transcription factors (KLFs). KLFs regulate axon growth in CNS neurons including retinal ganglion cells (RGCs). Here, we found that knock-down of KLF9, an axon growth suppressor that is normally upregulated 250-fold in RGC development, promotes long-distance optic nerve regeneration in adult rats of both sexes.

JUN is important for ocular hypertension-induced retinal ganglion cell degeneration.

Ocular hypertension, a major risk factor for glaucoma, is thought to trigger glaucomatous neurodegeneration through injury to retinal ganglion cell (RGC) axons. The molecular signaling pathway leading from ocular hypertension to RGC degeneration, however, is not well defined. JNK signaling, a component of the mitogen-activated protein kinase (MAPK) family, and its canonical target, the transcription factor JUN, have been shown to regulate neurodegeneration in many different systems.

Impact of Unrestricted Access to Pregabalin on the Use of Opioids and Other CNS-Active Medications: A Cross-Sectional Time Series Analysis.

Objective: Access to pregabalin via Ontario's public drug insurance program was expanded to an unrestricted model on April 1, 2013, from a prior authorization model. This study aims to identify the effect of expanded access on the rate of pregabalin use by publicly insured persons and to assess the characteristics of new patients initiating pregabalin following this expanded access.

Methods: We conducted a cross-sectional time series analysis using the linked health administrative records of residents of Ontario, Canada, with public drug coverage who were dispensed a prescription for pregabalin between April 1, 2006, and December 31, 2014.

The effect of surgery type on survival and recurrence in very young women with breast cancer.

Background: The impact of surgical treatment on outcomes in breast cacner in very young women remains unclear. We sought to determine the effect of surgery type on risk of recurrence and survival in a population-based cohort.

Methods: All women diagnosed with breast cancer aged ≤35 (1994-2003) were identified from the Ontario Cancer Registry.

High-Dose Opioid Prescribing and Opioid-Related Hospitalization: A Population-Based Study.

Aims: To examine the impact of national clinical practice guidelines and provincial drug policy interventions on prevalence of high-dose opioid prescribing and rates of hospitalization for opioid toxicity.

Design: Interventional time-series analysis.

Setting: Ontario, Canada, from 2003 to 2014.

Persistence of Antipsychotic Treatment in Elderly Dementia Patients: A Retrospective, Population-Based Cohort Study.

Background: Antipsychotics are commonly used to manage behavioral and psychological symptoms of dementia. Concerns over their safety and efficacy in this role have resulted in antipsychotics typically being recommended for short-term usage only when used among dementia patients. However, there is little work examining the duration of antipsychotic treatment in the elderly dementia patient population.

Small-area variation in screening for cancer, glucose and cholesterol in Ontario: a cross-sectional study.

Background: Screening for cervical, breast and colon cancers, and elevations of cholesterol and glucose, reduces premature cause-specific mortality from these cancers and circulatory diseases. Despite primary care reforms and incentives, and promotion of cancer-screening programs among individuals, participation is suboptimal. We aimed to examine participation as of Dec.

Cancer Mortality Among Recipients of Solid-Organ Transplantation in Ontario, Canada.

Importance: Solid-organ transplant recipients (SOTRs) are at greater risk of developing some cancers than the general population; however, because they are also at increased risk of mortality from noncancer causes, the effect of transplantation on cancer mortality is unclear.

Objective: To describe cancer mortality in SOTRs and to assess whether SOTRs are at increased risk of cancer mortality compared with the general population.

Design, Setting, And Participants: Population-based cohort study of patients who underwent solid-organ transplantation in Ontario, Canada, between 1991 and 2010 with 85 557 person-years of follow-up through December 31, 2011.

Sensitivity and specificity of administrative mortality data for identifying prescription opioid-related deaths.

Background: Comprehensive systems for surveilling prescription opioid-related harms provide clear evidence that deaths from prescription opioids have increased dramatically in the United States. However, these harms are not systematically monitored in Canada. In light of a growing public health crisis, accessible, nationwide data sources to examine prescription opioid-related harms in Canada are needed.

Quantitative measurement of retinal ganglion cell populations via histology-based random forest classification.

The inner surface of the retina contains a complex mixture of neurons, glia, and vasculature, including retinal ganglion cells (RGCs), the final output neurons of the retina and primary neurons that are damaged in several blinding diseases. The goal of the current work was two-fold: to assess the feasibility of using computer-assisted detection of nuclei and random forest classification to automate the quantification of RGCs in hematoxylin/eosin (H&E)-stained retinal whole-mounts; and if possible, to use the approach to examine how nuclear size influences disease susceptibility among RGC populations. To achieve this, data from RetFM-J, a semi-automated ImageJ-based module that detects, counts, and collects quantitative data on nuclei of H&E-stained whole-mounted retinas, were used in conjunction with a manually curated set of images to train a random forest classifier.

Ticagrelor and bradycardia: a nested case-control study.

Purpose: Ticagrelor increases serum adenosine concentrations, slowing conduction and possibly leading to bradycardia. Clinical trial data have shown numerically, though not statistically significantly, higher rates of bradyarrhythmias with ticagrelor versus clopidogrel. Additionally, recent case reports have further raised concerns for this adverse effect.

Using genetic mouse models to gain insight into glaucoma: Past results and future possibilities.

While all forms of glaucoma are characterized by a specific pattern of retinal ganglion cell death, they are clinically divided into several distinct subclasses, including normal tension glaucoma, primary open angle glaucoma, congenital glaucoma, and secondary glaucoma. For each type of glaucoma there are likely numerous molecular pathways that control susceptibility to the disease. Given this complexity, a single animal model will never precisely model all aspects of all the different types of human glaucoma.

A population-based study of the drug interaction between clopidogrel and angiotensin converting enzyme inhibitors.

Aims: Clopidogrel and angiotensin converting enzyme (ACE) inhibitors are commonly co-prescribed drugs. Clopidogrel inhibits carboxylesterase 1 (CES1), the enzyme responsible for converting prodrug ACE inhibitors (such as ramipril and perindopril) to their active metabolites. The clinical implications of this potential drug interaction are unknown.

Geographic Variation Immediate and Delayed Breast Reconstruction Utilization in Ontario, Canada and Plastic Surgeon Availability: A Population-Based Observational Study.

Background: Utilization of breast reconstruction (BR) is low in many jurisdictions. We studied the geographical and surgical workforce factors that contribute to access and use of BR using a small area analysis approach with a geographical unit of analysis.

Methods: We linked administrative data from Ontario Canada to calculate the age-standardized rates for immediate BR (IBR) (same time as mastectomy) between 2002 and 2011, and delayed BR (DBR) (within 3 years of mastectomy) for each county.

Involvement of low- and middle-income countries in randomized controlled trial publications in oncology.

Background: We describe trends in participation by investigators from low- and middle-income countries (LMCs) in publications describing oncology randomized control trials (RCTs) over a decade.

Methods: We used Medline to identify RCTs published in English from 1998 to 2008 evaluating treatment in lung, breast, colorectal, stomach and liver cancers. Data on author affiliations, authorship roles, trial characteristics, funding and interventions were extracted from each article.

The impact of the use of aspirin and other nonsteroidal anti-inflammatory drugs on the risk of prostate cancer detection on biopsy.

Objective: To evaluate the association between nonsteroidal anti-inflammatory drug (NSAID) use and the risk of prostate cancer (PC) detection in men undergoing biopsy.

Methods: Men were identified using our academic institution's prospectively maintained prostate biopsy database. Patients were classified as aspirin (ASA) users, users of other NSAIDs, or nonusers.

Tumor necrosis factor alpha has an early protective effect on retinal ganglion cells after optic nerve crush.

Background: Glaucoma is an optic neuropathy that is characterized by the loss of retinal ganglion cells (RGCs) initiated by damage to axons in the optic nerve. The degeneration and death of RGCs has been thought to occur in two waves. The first is axogenic, caused by direct insult to the axon.

Cigarette smoke primes the pulmonary environment to IL-1α/CXCR-2-dependent nontypeable Haemophilus influenzae-exacerbated neutrophilia in mice.

Cigarette smoke has a broad impact on the mucosal environment with the ability to alter host defense mechanisms. Within the context of a bacterial infection, this altered host response is often accompanied by exacerbated cellular inflammation, characterized by increased neutrophilia. The current study investigated the mechanisms of neutrophil recruitment in a murine model of cigarette smoke exposure and, subsequently, a model of both cigarette smoke exposure and bacterial infection.