CD4/CD8 double negative pagetoid reticulosis: a case report and literature review

Pagetoid reticulosis is an indolent primary cutaneous T‐cell lymphoma. It typically presents as a solitary and slowly growing patch or plaque on the extremity, histologically characterized by an acanthotic epidermis infiltrated with atypical lymphocytes. Here, we present histological, immunophenotypical and molecular findings of a 29‐year‐old Jamaican man with bilateral wrist plaques. Histology showed marked acanthosis, hyperkeratosis and an intraepidermal infiltration consisting of large atypical lymphocytes. Immunohistochemical stains showed CD3 and CD5 positive T cells with significant loss of CD7, double negative CD4 and CD8 and strong positive CD30. Molecular analysis showed a monoclonal T‐cell receptor (TCR) gamma gene rearrangement. Review of the literature confirms that the immunophenotype of pagetoid reticulosis is variable with decreasing frequency of CD8+ cytotoxic/suppressor T cell, CD4+ helper T cell and least commonly CD4/CD8 double negative phenotypes. Although CD4/CD8 double negative phenotype appears to be associated with higher proliferation index, it does not appear to confer prognostic significance. Mourtzinos N, Puri PK, Guanghua W, Liu M‐L. CD4/CD8 double negative pagetoid reticulosis: a case report and literature review.     

Climate change: The implications for child health in Australasia

Children are particularly vulnerable to the health effects of climate change, the biggest global health threat of the 21st century. However, the worst effects on child health can be avoided, and well‐designed climate policies can have important benefits for child health and equity. We call on child health professionals to seize opportunities to prevent climate change, improve child health and reduce inequalities, and suggest useful actions that can be taken.     

Identification With Terrorist Victims of the Washington,DC Sniper Attacks: Posttraumatic Stress and Depression

In October 2002, a series of sniper attacks in the Washington, DC area left 10 people dead and 3 wounded. We examined the association between identification with terrorist victims and psychological and behavioral outcomes. Participants were 1,238 residents of the Washington, DC area (ages 18–90 years; M = 41.73, SD = 12.56) who completed the Impact of Event Scale‐Revised, Patient Health Questionnaire‐9, and items pertaining to identification with attack victims approximately 3 weeks following the first sniper shooting. We examined 3 types of identification with the victims: (a) as like oneself, (b) as like a friend, and (c) as like a family member. The relationships of identification to posttraumatic stress and depressive symptoms were examined using linear regression analyses. Greater total identification was associated with more posttraumatic stress and depressive symptoms (B = 0.27, p < .001, and B = 0.44, p < .001, respectively), after adjusting for demographics. Those who specifically identified with the victims as either self (B = 0.24, p < .001), friend (B = 0.30, p < .001), or family member (B = 0.27, p < .001) reported more PTSD symptoms (n = 1,101). Identifying with victims as like a friend or family member, but not as like oneself, was associated with increased depressive symptoms (B = 0.61, p < .001, and B = 0.45, p = .01, respectively; n = 1,222). Presence and type of identification play a differential role in psychological and behavioral responses during traumatic events.     

Rasch Analysis of Patient- and Parent-Reported Outcome Measures in the International Consortium for Health Outcomes Measurement Standard Set for Cleft Lip and Palate

ObjectivesThe aim of this study was to evaluate the psychometric performance of the patient- and parent-reported measures in the International Consortium for Health Outcomes Measurement (ICHOM) Standard Set for Cleft Care, and to identify ways of improving concept coverage.MethodsData from 714 patients with cleft lip and/or palate, aged 8 to 9, 10 to 12.5, and 22 years were collected between November 2015 and April 2019 at Erasmus University Medical Center, Boston Children’s Hospital, Duke Children’s Hospital, and from participating sites in the CLEFT-Q Phase 3 study. The Standard Set includes 9 CLEFT-Q scales, the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire, the Child Oral Health Impact Profile–Oral Symptoms Scale (COHIP-OSS), and the Intelligibility in Context Scale (ICS). Targeting, item-fit statistics, thresholds for item responses, and measurement precision (PSI) were analyzed using Rasch measurement theory.ResultsThe proportion of the sample to score within each instruments range of measurement varied from 69% (ICS) to 92% (CLEFT-Q teeth and COHIP-OSS). Specific problems with individual items within the NOSE and COHIP-OSS questionnaires were noted, such as poor item fit to the Rasch model and disordered thresholds (6 of 10). Reliability measured with PSI was above 0.82 for the ICS and all but one CLEFT-Q scale (speech distress). PSIs were lowest for the COHIP-OSS (0.43) and NOSE questionnaire (0.35).ConclusionThe patient- and parent-reported components within the facial appearance, psychosocial function, and speech domains are valid measures; however, the facial function and oral health domains are not sufficiently covered by the CLEFT-Q eating and drinking, NOSE, and COHIP-OSS, and these questionnaires may not be accurate enough to stratify cleft-related outcomes.     

Frontoparietal mechanisms supporting attention to location and intensity of painful stimuli

Attention can profoundly shape the experience of pain. However, little is known about the neural mechanisms that support directed attention to nociceptive information. In the present study, subjects were cued to attend to either the spatial location or the intensity of sequentially presented pairs of painful heat stimuli during a delayed match-to-sample discrimination task. We hypothesized that attention-related brain activation would be initiated after the presentation of the attentional cue and would be sustained through the discrimination task. Conjunction analysis confirmed that bilateral portions of the posterior parietal cortex (intraparietal sulcus [IPS] and superior parietal lobule) exhibited this sustained activity during attention to spatial but not intensity features of pain. Analyses contrasting activation during spatial and intensity attention tasks revealed that the right IPS region of the posterior parietal cortex was consistently more activated across multiple phases of the spatial task. However, attention to either feature of the noxious stimulus was associated with activation of frontoparietal areas (IPS and frontal eye fields) as well as priming of the primary somatosensory cortex. Taken together, these results delineate the neural substrates that support selective amplification of different features of noxious stimuli for utilization in discriminative processes.     

RNA-Seq analysis in an avian model of maternal phenylketonuria

Cardiac malformations (CVMs) are a leading cause of infant morbidity and mortality. CVMs are particularly prevalent when the developing fetus is exposed to high levels of phenylalanine in-utero in mothers with Phenylketonuria. Yet, elucidating the underlying molecular mechanism leading to CVMs has proven difficult. In this study we used RNA-Seq to investigate an avian model of MPKU and establish differential gene expression (DEG) characteristics of the early developmental stages HH10, 12, and 14. In total, we identified 633 significantly differentially expressed genes across stages HH10, 12, and 14. As expected, functional annotation of significant DEGs identified associations seen in clinical phenotypes of MPKU including CVMs, congenital heart defects, craniofacial anomalies, central nervous system defects, and growth anomalies. Additionally, there was an overrepresentation of genes involved in cardiac muscle contraction, adrenergic signaling in cardiomyocytes, migration, proliferation, metabolism, and cell survival. Strikingly, we identified significant changes in expression with multiple genes involved in Retinoic Acid (RA) metabolism and downstream targets. Using qRTPCR, we validated these findings and identified a total of 42 genes within the RA pathway that are differentially expressed. Here, we report the first elucidation of the molecular mechanisms of cardiovascular malformations in MPKU conducted at early developmental timepoints. We provide evidence suggesting a link between PHE exposure and the alteration of RA pathway. These results are promising and offer novel findings associated with congenital heart defects in MPKU.     

Offset analgesia: a temporal contrast mechanism for nociceptive information

Temporal filtering of afferent information is an intrinsic component of the processing of numerous types of sensory information. To date, no temporal filtering mechanism has been identified for nociceptive information. The phenomenon of offset analgesia, the disproportionately large decrease in perceived pain following slight decreases in noxious thermal intensity, however, suggests the existence of such a mechanism. To test the hypothesis that a temporal filtering mechanism is engaged during noxious stimulus offset, subjects rated heat pain intensity while stimulus fall rates were varied from -0.5 to -5.0 degrees C/s. In the absence of a temporal filtering mechanism, pain intensity would be expected to decrease in direct proportion to the stimulus fall rate. However, psychophysical fall rates were considerably faster than stimulus fall rates, such that subjects reported no pain while stimulus temperatures were clearly within the noxious range (47.2 degrees C). In addition, paired noxious stimuli were presented simultaneously to determine if offset analgesia evoked by one stimulus could inhibit pain arising from a separate population of primary afferent neurons. Pain ratings were significantly lower than those reported from two constant 49 degrees C stimuli when offset analgesia was induced proximal to, but not distal to, a second noxious stimulus. These asymmetric spatial interactions are not readily explained by peripheral mechanisms. Taken together, these findings indicate that offset analgesia is mediated in part by central mechanisms and reflect a temporal filtering of the sensory information that enhances the contrast of dynamic decreases in noxious stimulus intensity.