Epidermodysplasia Verruciformis in Lipoid Proteinosis: Case Report and Discussion of Pathophysiology

Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis caused by mutations in extracellular matrix protein 1 (ECM1) that involves deposition of basement membrane–like material in the skin and other organs. Epidermodysplasia verruciformis (EV) is also a rare autosomal recessive genodermatosis involving susceptibility to human papillomavirus (HPV) infections and squamous cell carcinoma, caused in most cases by homozygous mutations in EVER1 or EVER2. We describe a case of EV in a patient with LP and discuss the pathophysiology. A 3‐year‐old Lebanese girl presented with hoarseness, beaded papules along the eyelid margins, waxy papules and plaques on her head and neck, and lichenoid verrucous papules on the forearms and hands. Histopathology of the waxy papules exhibited deposition of periodic acid Schiff–positive basement membrane–like material in the superficial dermis, characteristic of LP. The verruca plana–like lesions exhibited acanthosis and enlarged keratinocytes with pale blue‐grey cytoplasm and a perinuclear halo, consistent with verrucae and EV. Polymerase chain reaction amplification and sequencing of ECM1, EVER1, and EVER2 demonstrated a homozygous point mutation, c.389C>T (p.Thr130Met), in exon 6 of ECM1 and a heterozygous point mutation, c.917 A>T (p.Asn306Ile), in exon 8 in EVER2, known to cause EV in homozygous patients. The homozygous point mutation c.389C>T in ECM1 may be a novel mutation causing LP. Verruca plana–like lesions seen in LP appear to represent a form of acquired EV. In this patient, a heterozygous mutation in EVER2 at c.917 A>T may also have conferred susceptibility to HPV infection.     

Treatment of a second maxillary molar with six canals

Variations in the dental anatomy are found in all teeth. Knowledge of these variations, particularly concerning the location and treatment of all canals, is very important for the success of the endodontic therapy. The purpose of this study is to present a clinical case of a maxillary second molar with three palatal canals, two mesio-buccal and one disto-buccal canal. This report serves to remind clinicians that such anatomical variations should be taken into account during endodontic treatment of the maxillary molars.     

Synergy between mu opioid ligands: evidence for functional interactions among mu opioid receptor subtypes

Pharmacological differences among mu opioid drugs have been observed in in vitro and in vivo preclinical models, as well as clinically, implying that all mu opioids may not be working through the same mechanism of action. Here we demonstrate analgesic synergy between L-methadone and several mu opioid ligands. Of the compounds examined, L-methadone selectively synergizes with morphine, morphine-6beta-glucuronide, codeine, and the active metabolite of heroin, 6-acetylmorphine. Morphine synergizes only with L-methadone. In analgesic assays, D-methadone was inactive alone and did not enhance morphine analgesia when the two were given together, confirming that L-methadone was not acting through N-methyl-D-aspartate mechanisms. Both L-methadone and morphine displayed only additive effects when paired with oxymorphone, oxycodone, fentanyl, alfentanyl, or meperidine. Although it displays synergy in analgesic assays, the L-methadone/morphine combination does not exhibit synergy in the gastrointestinal transit assay. This analgesic synergy of L-methadone with selective mu opioid drugs and the differences in opioid-mediated actions suggest that these drugs may be acting via different mechanisms. These findings provide further evidence for the complexity of the pharmacology of mu opioids.     

Isolating and characterizing three alternatively spliced mu opioid receptor variants: mMOR‐1A,mMOR‐1O,and mMOR‐1P

Extensive alternative pre‐mRNA splicing of the mu opioid receptor gene, OPRM1, has demonstrated an array of splice variants in mice, rats and humans. Three classes of splice variants have been identified: full‐length seven transmembrane (TM) domain variants with C‐terminal splicing, truncated 6TM variants and single TM variants. The current studies isolates and characterizes an additional three full‐length C‐terminal splice variants generated from the mouse OPRM1 gene: mMOR‐1A, mMOR‐1O, and mMOR‐1P. Using RT‐qPCR, we demonstrated differential expression of these variants' mRNAs among selected brain regions, supporting region‐specific alternative splicing. When expressed in Chinese Hamster Ovary cells, all the variants displayed high mu binding affinity and selectivity with subtle differences in the affinities toward some agonists. [³⁵S]γGTP binding assays revealed marked differences in agonist‐induced G protein activation in both potency and efficacy among the variants. Together with the previous studies of mu agonist‐induced phosphorylation and internalization in several carboxyl terminal splice variants, the current studies further suggest the existence of biased signaling of various agonists within each individual variant and/or among different variants. Synapse 68:144–152, 2014 . © 2013 Wiley Periodicals, Inc.     

REPIMPACT - a prospective longitudinal multisite study on the effects of repetitive head impacts in youth soccer

Brain Imaging and Behavior - Repetitive head impacts (RHI) are common in youth athletes participating in contact sports. RHI differ from concussions; they are considered hits to the head that...     

Diastolic blood pressure is the first to rise in association with early subclinical obstructive sleep apnea: lessons from periodic examination screening

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with long-term cardiovascular morbidity. Little is known about these relations at early stages. We conducted a case-control study in which we analyzed the clinical characteristics of young adults who underwent a periodic health examination and were screened for, and eventually found to experience, OSAS. METHODS: We identified 121 subjects newly diagnosed in a sleep study as having OSAS, and 229 matched control subjects in which screening for OSAS was negative. All had a medical interview, physical examination, and routine laboratory tests. RESULTS: Subjects who had OSAS had a higher, body mass index (3-kg/m(2) difference) and a higher diastolic blood pressure (4-mm Hg difference) value, without elevation in systolic blood pressure. There was no metabolic difference (lipids profile and fasting glucose levels) between groups. CONCLUSIONS: Diastolic blood pressure is higher early in the course of OSAS. Long term follow-up may determine effects of prevention and early intervention in OSAS and associated hypertension.