Doctored photographs create false memories of spectacular childhood events. a replication of Wade et al. (2002) with a Scandinavian twist.

ABSTRACTCan exposure to a doctored photograph of a plausible yet fictitious childhood event create false memories in adults? Twenty years ago, (Wade, K. A., Garry, M., Don Read, J., & Lindsay, D. S. (2002). A picture is worth a thousand lies: Using false photographs to create false childhood memories. Psychonomic Bulletin & Review, 9(3), 597-603) found that half of the participants reported false beliefs or memories after multiple interview sessions about a doctored photograph of themselves as children on a fictitious hot air balloon ride. In this replication, which rigorously recreated the method and procedure of Wade et al. (2002), participants were interviewed over three interview sessions using free recall and imagery techniques about three true and one fictitious childhood event photos. The balloon ride was modified to a culturally appropriate target event - a Viking ship ride - to ensure that the doctored photograph was functionally equivalent. The results showed almost identical patterns in the two studies: 40% (n = 8) of the participants reported partial or clear false beliefs or memories compared with 50% (n = 10) in the original study. The participants who reported false memories reported detailed and coherent memory narratives of the Viking ship ride not depicted in the doctored photograph. Our study successfully replicating the results of Wade et al. (2002), suggest that memories can relatively easily be implanted, regardless of cultural setting.

Title: Novel Analgesic Potential of ß2-Agonists for Neuropathic Pain via ß2-Agonist Action.

PURPOSE OF REVIEW: Multimodal therapies are often employed to treat chronic pain, and ß2-agonists are a potential drug class that shows promise. The primary aim of this paper is to discuss the role of ß2-agonists as an adjunctive therapy for chronic pain based on the current literature. RECENT FINDINGS: Recent studies in mouse models have shown that the ß2-adrenergic system plays an essential role in the analgesic properties of antidepressant drugs used to treat neuropathic pain and that the adrenergic relies on an intact endogenous opioid system to be effective. Studies also show that ß2-agonism alone is adequate to exert anti-allodynic effects in a mouse model. This paper summarized the basic physiology and pharmacology of the sympathetic nervous system and specifically the ß2-adrenergic system and summarized current literature in its involvement in the treatment of chronic neuropathic pain.

SON drives oncogenic RNA splicing in glioblastoma by regulating PTBP1/PTBP2 switching and RBFOX2 activity.

While dysregulation of RNA splicing has been recognized as an emerging target for cancer therapy, the functional significance of RNA splicing and individual splicing factors in brain tumors is poorly understood. Here, we identify SON as a master regulator that activates PTBP1-mediated oncogenic splicing while suppressing RBFOX2-mediated non-oncogenic neuronal splicing in glioblastoma multiforme (GBM). SON is overexpressed in GBM patients and SON knockdown causes failure in intron removal from the PTBP1 transcript, resulting in PTBP1 downregulation and inhibition of its downstream oncogenic splicing. Furthermore, SON forms a complex with hnRNP A2B1 and antagonizes RBFOX2, which leads to skipping of RBFOX2-targeted cassette exons, including the PTBP2 neuronal exon. SON knockdown inhibits proliferation and clonogenicity of GBM cells in vitro and significantly suppresses tumor growth in orthotopic xenografts in vivo. Collectively, our study reveals that SON-mediated RNA splicing is a GBM vulnerability, implicating SON as a potential therapeutic target in brain tumors.

Clinical albinism score, presence of nystagmus and optic nerves defects are correlated with visual outcome in patients with oculocutaneous albinism.

Purpose: To correlate clinical features, molecular genetic findings, and visual acuity in a cohort of patients clinically diagnosed with oculocutaneous albinism.Design: Retrospective chart reviewMethods: 58 charts met the inclusion criteria. Clinical examination, ancillary testing, and molecular genetic diagnoses were extracted. A novel clinical albinism score (CAS) was developed.Results: A least one likely pathogenic mutation was found in 44/58 (75.9%) patients. Mutations in the OCA1 gene were the most common (52.3%), followed by OCA2 (34%), OCA4 (2.3%), OA1 (6.8%), and HPS (4.5%). Thirty-four percentage of patients had a complete genotype, 41% had one mutation found and 24% had negative genetic testing. CAS was statistically significantly higher in patients with complete genotype, versus patients with one or no mutations found (p < .01). Better visual acuity was associated with lower CAS and fewer disease-causing mutations (p < .01). Foveal defects and iris transillumination were associated with a higher number of mutations (p < .01). Patients with nystagmus or anomalous optic nerves had worse visual acuity than those who did not (p < .01, p < .05).Conclusions: Patients with a complete genotype were more likely to have higher CAS. Vision loss correlated with complete phenotype and higher CAS, the presence of nystagmus and anomalous optic nerves. Patients with features of albinism in whom an incomplete genotype was found had better vision than those with complete genotype, suggesting a mild occult mutation or modifier variant. Genetic diagnosis is vital for complete diagnosis, counseling, and family planning.

Evaluation of masticatory muscle response to clear aligner therapy using ambulatory electromyographic recording.

INTRODUCTION: Patients undergoing clear aligner therapy (CAT) report muscle tenderness and produce wear facets on their aligner trays. However, little is known about the masticatory muscle response to clear aligners. Here, we measured the activity of the masseter during CAT using ambulatory electromyography. We also explored whether psychological traits modulate the masticatory muscle response to CAT. METHODS: Using portable data loggers, we recorded the electromyographic (EMG) activity in the right masseter muscle of 17 healthy adults without temporomandibular disorder (16 females, 1 male; mean age ± standard deviation, 35.3 ± 17.6 years) commencing treatment with CAT over 4 weeks, under the following conditions: week 1 without aligners (baseline), week 2 with a passive aligner (dummy), week 3 with their first active aligner (active1), and week 4 with their second active aligner (active2). We used a mixed-effect model to test differences in EMG activity over the 4-weeks and a general linear model to test the effect of psychological traits on EMG activity. RESULTS: The EMG activity of the masseter increased significantly with aligners compared with baseline. The largest relative increase in EMG activity was seen during the dummy (152%; P <0.001) and active1 (155%; P <0.001) stages. During active2, the activity of the masseter decreased significantly toward baseline levels. Participants' trait anxiety was positively associated with increases in EMG activity (P = 0.027). CONCLUSIONS: CAT is associated with a transient increase in masticatory muscle activity, possibly because of an increase in wake-time parafunctional tooth clenching. Temporomandibular disorder-free patients adapt well to CAT as the masticatory muscle activity decreases toward baseline levels after 2 weeks.

SON inhibits megakaryocytic differentiation via repressing RUNX1 and the megakaryocytic gene expression program in acute megakaryoblastic leukemia.

A high incidence of acute megakaryoblastic leukemia (AMKL) in Down syndrome patients implies that chromosome 21 genes have a pivotal role in AMKL development, but the functional contribution of individual genes remains elusive. Here, we report that SON, a chromosome 21-encoded DNA- and RNA-binding protein, inhibits megakaryocytic differentiation by suppressing RUNX1 and the megakaryocytic gene expression program. As megakaryocytic progenitors differentiate, SON expression is drastically reduced, with mature megakaryocytes having the lowest levels. In contrast, AMKL cells express an aberrantly high level of SON, and knockdown of SON induced the onset of megakaryocytic differentiation in AMKL cell lines. Genome-wide transcriptome analyses revealed that SON knockdown turns on the expression of pro-megakaryocytic genes while reducing erythroid gene expression. Mechanistically, SON represses RUNX1 expression by directly binding to the proximal promoter and two enhancer regions, the known +23 kb enhancer and the novel +139 kb enhancer, at the RUNX1 locus to suppress H3K4 methylation. In addition, SON represses the expression of the AP-1 complex subunits JUN, JUNB, and FOSB which are required for late megakaryocytic gene expression. Our findings define SON as a negative regulator of RUNX1 and megakaryocytic differentiation, implicating SON overexpression in impaired differentiation during AMKL development.

Impact of clear aligner therapy on tooth pain and masticatory muscle soreness.

BACKGROUND: Clinical findings suggest that orthodontic treatment with clear aligners (clear aligner therapy/CAT) may cause masticatory muscle soreness in some patients. OBJECTIVE: This multi-site prospective study investigated tooth pain and masticatory muscle soreness and tenderness in patients undergoing CAT and explored whether psychological traits affected these outcomes. METHODS: Twenty-seven adults (22F, 5M; mean age ± SD=35.3 ± 17.6 years) about to start CAT were recruited at three clinics. During CAT, they reported on 100-mm visual analogue scales their tooth pain, masticatory muscle soreness and stress three times per day over 4 weeks (week 1 = baseline; week 2 = dummy aligner; week 3 = first active aligner; week 4 = second active aligner). Pressure pain thresholds (PPTs) were measured at the masseter and temporalis at baseline and after week 4. Mixed models were used to evaluate the outcome measures over time. RESULTS: Clear aligner therapy caused mild tooth pain, which was greater with the passive than the first and second active aligners (both P < .001). Mild and clinically not relevant masticatory muscle soreness was produced by all aligners (all P < .05), with the first active aligner producing less soreness than the dummy aligner (P < .001). PPTs did not change significantly after 4 weeks. Both tooth pain and masticatory muscle soreness were affected by stress and trait anxiety, whilst muscle soreness was affected also by oral behaviours. CONCLUSIONS: In the short term, CAT produces tooth pain and masticatory muscle soreness of limited significance. Frequent oral behaviours are related to increased masticatory muscle soreness during CAT. The medium- and long-term effects of CAT should be further explored.

Targeted metabolomic approach for assessing human synthetic cannabinoid exposure and pharmacology.

Designer synthetic cannabinoids like JWH-018 and AM2201 have unique clinical toxicity. Cytochrome-P450-mediated metabolism of each leads to the generation of pharmacologically active (ω)- and (ω-1)-monohydroxyl metabolites that retain high affinity for cannabinoid type-1 receptors, exhibit Δ(9)-THC-like effects in rodents, and are conjugated with glucuronic acid prior to excretion in human urine. Previous studies have not measured the contribution of the specific (ω-1)-monohydroxyl enantiomers in human metabolism and toxicity. This study uses a chiral liquid chromatography-tandem mass spectroscopy approach (LC-MS/MS) to quantify each specific enantiomer and other nonchiral, human metabolites of JWH-018 and AM2201 in human urine. The accuracy (average % RE = 18.6) and reproducibility (average CV = 15.8%) of the method resulted in low-level quantification (average LLQ = 0.99 ng/mL) of each metabolite. Comparisons with a previously validated nonchiral method showed strong correlation between the two approaches (average r(2) = 0.89). Pilot data from human urine samples demonstrate enantiospecific excretion patterns. The (S)-isomer of the JWH-018-(ω-1)-monohydroxyl metabolite was predominantly excreted (>87%) in human urine as the glucuronic acid conjugate, whereas the relative abundance of the corresponding AM2201-(ω-1)-metabolite was low (<5%) and did not demonstrate enantiospecificity (approximate 50:50 ratio of each enantiomer). The new chiral method provides a comprehensive, targeted metabolomic approach for studying the human metabolism of JWH-018 and AM2201. Preliminary evaluations of specific enantiomeric contributions support the use of this approach in future studies designed to understand the pharmacokinetic properties of JWH-018 and/or AM2201.

Historical, spatial, temporal, and time-space epidemiology of very virulent infectious bursal disease in California: a retrospective study 2008-2011.

In December of 2008 very virulent infectious bursal disease virus (vvIBDV) was identified in a commercial flock in northern California. Since then several other backyard and commercial facilities in California have had flocks affected by the same strain and other unique (previously unseen) strains of IBDV. Previous to this incident, very virulent infectious bursal disease (vvIBD) had never been identified in North America. Following the initial outbreak in 2008, California became the first state to undertake a voluntary surveillance effort to try to determine the geographical prevalence of vvIBD based on sequencing of a portion of the segment A region of the vvIBDV genome. To date we have complete geographical information on approximately 500 separate accessions representing approximately 1500 birds from over 200 commercial (-85% of the facilities) and backyard facilities (-15% of the facilities) throughout the state. Sequencing of targeted regions of both the segment A and segment B regions of the genome has revealed three distinct types of IBDV in California chickens. One type is genetically and in pathogenically consistent with vvIBDV. The second and third types only have a segment A region consistent with vvIBDV. Geographic information system mapping coupled with spatial-temporal cluster analysis identified significant spatial and time-space clustering; however, no temporal clustering was noted. The lack of temporal clustering coupled with negative vvIBDV results in tested avian wildlife implies that avian wildlife in California do not currently appear to play a significant role in vvIBDV transmission. In the voluntary surveillance that was done in the Central Valley of California, which has a high density of commercial poultry, no positive farms were found when 142 of 504 farms were sampled. Given this level of sampling, the confidence (probability) of detecting an affected commercial flock was calculated to be between 28% and 81% depending on whether one or five hypothetically affected farms were affected.