Changes in expression of sensory organ-specific microRNAs in rat dorsal root ganglia in association with mechanical hypersensitivity induced by spinal nerve ligation

Chronic neuropathic pain caused by peripheral nerve injury is associated with global changes in gene expression in damaged neurons. To understand the molecular mechanisms underlying neuropathic pain, it is essential to elucidate how nerve injury alters gene expression and how the change contributes to the development and maintenance of chronic pain. MicroRNAs are non-protein-coding RNA molecules that regulate gene expression in a wide variety of biological processes mainly at the level of translation. This study investigated the possible involvement of microRNAs in gene regulation relevant to neuropathic pain. The analyses focused on a sensory organ-specific cluster of microRNAs that includes miR-96, −182, and −183. Quantitative real-time polymerase chain reaction (qPCR) analyses confirmed that these microRNAs were highly enriched in the dorsal root ganglion (DRG) of adult rats. Using the L5 spinal nerve ligation (SNL) model of chronic neuropathic pain, we observed a significant reduction in expression of these microRNAs in injured DRG neurons compared to controls. In situ hybridization and immunohistochemical analyses revealed that these microRNAs are expressed in both myelinated (N52 positive) and unmyelinated (IB4 positive) primary afferent neurons. They also revealed that the intracellular distributions of the microRNAs in DRG neurons were dramatically altered in animals with mechanical hypersensitivity. Whereas microRNAs were uniformly distributed within the DRG soma of non-allodynic animals, they were preferentially localized to the periphery of neurons in allodynic animals. The redistribution of microRNAs was associated with changes in the distribution of the stress granule (SG) protein, T-cell intracellular antigen 1 (TIA-1). These data demonstrate that SNL induces changes in expression levels and patterns of miR-96, −182, and −183, implying their possible contribution to chronic neuropathic pain through translational regulation of pain-relevant genes. Moreover, SGs were suggested to be assembled and associated with microRNAs after SNL, which may play a role in modification of microRNA-mediated gene regulation in DRG neurons.     

Reliability and Validity of HeartSmartKids: A Survey of Cardiovascular Risk Factors in Children

Introduction

Reliable and valid instruments to measure counseling effectiveness related to eating, activity, and inactivity are lacking. HeartSmartKids (HSK; HeartSmartKids, LLC, Boulder, Colorado) is a bilingual decision-support technology that can be used to assess and counsel families on cardiovascular risk factors in children. The purpose of this study was to establish preliminary test–retest reliability and convergent validity of HSK questions relative to a previously validated questionnaire, HABITS.

Nucleotide excision repair genes and risk of lung cancer among San Francisco Bay Area Latinos and African Americans

Few studies on the association between nucleotide excision repair (NER) variants and lung cancer risk have included Latinos and African Americans. We examine variants in 6 NER genes (ERCC2, ERCC4, ERCC5, LIG1, RAD23B and XPC) in association with primary lung cancer risk among 113 Latino and 255 African American subjects newly diagnosed with primary lung cancer from 1998 to 2003 in the San Francisco Bay Area and 579 healthy controls (299 Latinos and 280 African Americans). Individual single nucleotide polymorphism and haplotype analyses, multifactor dimensionality reduction (MDR) and principal components analysis (PCA) were performed to assess the association between 6 genes in the NER pathway and lung cancer risk. Among Latinos, ERCC2 haplotype CGA (rs238406, rs11878644, rs6966) was associated with reduced lung cancer risk [odds ratio (OR) of 0.65 and 95% confidence interval (CI): 0.44-0.97], especially among nonsmokers (OR = 0.29; 95% CI: 0.12-0.67). From MDR analysis, in Latinos, smoking and 3 SNPs (ERCC2 rs171140, ERCC5 rs17655 and LIG1 rs20581) together had a prediction accuracy of 67.4% (p = 0.001) for lung cancer. Among African Americans, His/His genotype of ERCC5 His1104Asp (rs17655) was associated with increased lung cancer risk (OR = 1.78; 95% CI: 1.09-2.91), and LIG1 haplotype GGGAA (rs20581, rs156641, rs3730931, rs20579 and rs439132) was associated with reduced lung cancer risk (OR = 0.61; 95% CI: 0.42-0.88). Our study suggests different elements of the NER pathway may be important in the different ethnic groups resulting either from different linkage relationship, genetic backgrounds and/or exposure histories.     

Segmental fracture of the scaphoid: report of a rare fracture pattern

Introduction:To the best of our knowledge, there are no reports in the orthopaedic and trauma literature of true segmental fracture of the scaphoid bone. We present such a case with a brief discussion of the morphology and mechanisms of injury of scaphoid fractures and the problems they present, particularly in diagnosis. Case history: A 43-year-old male with polytrauma sustained in a motorcycle road traffic accident was treated at our hospital. His injuries included a fracture initially thought to involve the waist of the scaphoid. Because he had bilateral upper limb injuries, we elected to treat the fracture surgically to facilitate rehabilitation. At the time of surgery, the fracture was noted to be truly segmental, an unsuspected and rare finding. The fracture was internally fixed, with a satisfactory result. Discussion: Scaphoid fracture patterns are generally consistent and predictable, occurring most commonly through the waist of the bone. Mechanism for injury is thought to be hyperextension of the wrist. Comminution, with or without a butterfly fragment, is occasionally seen, as are simultaneous tuberosity fractures. We suggest that the mechanism in this case may have been multiple or secondary trauma, or an effect of loaded rotation. We highlight the need for careful imaging of the scaphoid bone prior to choosing treatment.     

Smoking cessation in the elderly

Today, two generations after the first Surgeon General's report, and with abundant evidence of the catastrophic consequences of smoking, no serious person can be unaware that smokers risk their lives and health. We also know that quitting smoking--at any age--promises significant health benefits. When offered the tools they need, older smokers quit smoking at rates comparable to those of younger smokers despite their skepticism, fatalism, and self-doubt. Older smokers should be encouraged to enter programs that stress the health benefits derived and identify the risks they are avoiding by quitting smoking. These programs establish quit dates, use sound behavioral modification techniques, provide strategies for stress management and relaxation, treat withdrawal symptoms, and provide regular and continuing follow-up. The patient is asked to make an existential change, and the physician should provide encouragement and promote self-confidence by emphasizing that, despite setbacks, with repeated efforts, success can be achieved. Clinicians can influence patients to quit smoking, and they should.     

Drugs and receptors

There are four principle protein targets with which drugs caninteract: enzymes (e.g. neostigmine and acetyl cholinesterase),membrane carriers (e.g. tricyclic antidepressants and catecholamineuptake-1), ion channels (e.g. nimodipine and voltage-gated Ca²⁺channels) and receptors. This article is concerned with thereceptor and describes the dynamics of drug–receptor interaction,agonists, antagonists, partial agonists and inverse agonists,efficacy and potency. Key definitions are shown in Table 1. View this table: [in this window] [in a new window]   Table 1 Key definitions