Epithelial membrane protein 2 (EMP2) deficiency alters placental angiogenesis, mimicking features of human placental insufficiency.

Epithelial membrane protein-2 (EMP2) is a tetraspan protein predicted to regulate placental development. Highly expressed in secretory endometrium and trophectoderm cells, previous studies suggest that it may regulate implantation by orchestrating the surface expression of integrins and other membrane proteins. In order to test the role of EMP2 in pregnancy, mice lacking EMP2 (Emp2-/- ) were generated. Emp2-/- females are fertile but have reduced litter sizes when carrying Emp2-/- but not Emp2+/- fetuses. Placentas of Emp2-/- fetuses exhibit dysregulation in pathways related to neoangiogenesis, coagulation, and oxidative stress, and have increased fibrin deposition and altered vasculature. Given that these findings often occur due to placental insufficiency resulting in an oxygen-poor environment, the expression of hypoxia-inducible factor-1 alpha (HIF-1α) was examined. Placentas from Emp2-/- fetuses had increased total HIF-1α expression in large part through an increase in uterine NK (uNK) cells, demonstrating a unique interplay between uNK cells and trophoblasts modulated through EMP2. To determine if these results translated to human pregnancy, placentas from normal, term deliveries or those complicated by placental insufficiency resulting in intrauterine growth restriction (IUGR) were stained for EMP2. EMP2 was significantly reduced in both villous and extravillous trophoblast populations in IUGR placentas. Experiments in vitro using human trophoblast cells lines indicate that EMP2 modulates angiogenesis by altering HIF-1α expression. Our results reveal a novel role for EMP2 in regulating trophoblast function and vascular development in mice and humans, and suggest that it may be a new biomarker for placental insufficiency. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The Efficacy of Q-Switched ND:YAG 1064 nm Laser in Recalcitrant Macular Amyloidosis: A Case Report.

Macular amyloidosis typically presents as small, dusky-brown or greyish pigmented macules, the result of altered keratin deposition. Treatment of these hyperpigmented regions with topical and systemic therapies remains challenging, however Q-Switched neodymi- um-doped yttrium aluminum garnet (ND:YAG) laser has proven to be an effective treatment modality to reduce hyperpigmentation. In this case report we investigated the ef cacy of Q-Switched Nd:YAG laser treatment on a 34-year old woman with recalcitrant macular amyloidosis who failed to respond to over-the-counter bleaching creams. The patient was treated with 7 treatment sessions of Q- Switched Nd:YAG laser at one month intervals. According to our photographic analysis and patient self-assessment, the patient ap- peared to improve with each treatment session. Post-recurrence of the lesion after reaction to Triluma ( uocoinolone actetonide 0.01%, hydroquinone 4%, tretinoin 0.05%), the patient has been continuing to respond well to a second round of treatment with Q-switched Nd:YAG laser at 1064 nm. J Drugs Dermatol. 2016;15(11):1456-1458..

Accurate pain reporting training diminishes the placebo response: Results from a randomised, double-blind, crossover trial.

Analgesic trials frequently fail to demonstrate efficacy of drugs known to be efficacious. Poor pain reporting accuracy is a possible source for this low essay-sensitivity. We report the effects of Accurate-Pain-Reporting-Training (APRT) on the placebo response in a trial of Pregabalin for painful-diabetic-neuropathy. The study was a two-stage randomized, double-blind trial: In Stage-1 (Training) subjects were randomized to APRT or No-Training. The APRT participants received feedback on the accuracy of their pain reports in response to mechanical stimuli, measured by R-square score. In Stage-2 (Evaluation) all subjects entered a placebo-controlled, cross-over trial. Primary (24-h average pain intensity) and secondary (current, 24-h worst, and 24-h walking pain intensity) outcome measures were reported. Fifty-one participants completed the study. APRT patients (n = 28) demonstrated significant (p = 0.036) increases in R-square scores. The APRT group demonstrated significantly (p = 0.018) lower placebo response (0.29 ± 1.21 vs. 1.48 ± 2.21, mean difference ± SD = -1.19±1.73). No relationships were found between the R-square scores and changes in pain intensity in the treatment arm. In summary, our training successfully increased pain reporting accuracy and resulted in a diminished placebo response. Theoretical and practical implications are discussed.