Symptom Phenotype Research Articles

A Comprehensive Phenotype of Non-motor Impairments and Distribution of Alpha-Synuclein Deposition in Parkinsonism-Induced Mice by a Combination Injection of MPTP and Probenecid.

Parkinson’s disease (PD) is characterized by non-motor symptoms as well as motor deficits. The non-motor symptoms rarely appear individually and occur simultaneously with motor deficits or independently. However, a comprehensive research on the non-motor symptoms using an experimental model of PD remains poorly understood. The aim of the current study is to establish a chronic mouse model of PD mimicking the comprehensive non-motor symptoms of human PD by injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid (MPTP/p). The non-motor and motor symptoms were evaluated by performing buried food, short-term olfactory memory, hot plate, open field, tail suspension, Y maze, novel object recognition, bead expulsion, one-h stool collection, rotarod, rearing, catalepsy, and akinesia tests after 10 injections of MPTP/p into mice. The expression levels of α-synuclein, glial fibrillary acidic protein (GFAP), tyrosine hydroxylase (TH) or DJ-1 were analyzed by Western blotting or immunostaining. MPTP/p-treated mice achieved to reproduce the key features of non-motor symptoms including olfactory deficit, thermal hyperalgesia, anxiety, depression, cognitive decline, and gastrointestinal dysfunction in addition to motor deficits. The MPTP/p-treated mice also showed the high levels of α-synuclein and low levels of TH and DJ-1 in striatum, substantia nigra, olfactory bulb, hippocampus, amygdala, prefrontal cortex, locus coeruleus, or colon. In addition, the expression levels of phosphorylated-α-synuclein and GFAP were elevated in the striatum and substantia nigra in the MPTP/p-treated mice. Taken together, our study clarifies that the chronic MPTP/p-treated mice have a variety of non-motor dysfunctions as well as motor abnormalities by α-synuclein overexpression and dopaminergic depletion. Therefore, the study of comprehensive phenotypes of non-motor symptoms in one PD model would advance in-depth understandings of neuropathological alternations and contribute to future strategies for PD treatment.

Are some patient-perceived migraine triggers simply early manifestations of the attack?

ObjectiveTo study the agreement between self-reported trigger factors and early premonitory symptoms amongst a group of migraineurs in both spontaneous and pharmacologically provoked attacks.MethodsFifty-three subjects with migraine with and without aura, with ≤ 22 headache days/month, with spontaneous premonitory symptoms associated with migraine attacks were recruited nationally. A detailed history was taken by a study investigator to confirm diagnosis and extended phenotyping was performed to identify patient-reported triggers for migraine attacks, premonitory symptom phenotype and headache characteristics, using a standardised physician-administered questionnaire. The same subjects were exposed to a 0.5 mcg/kg/min nitroglycerin infusion over 20 min, to determine if similar migraine symptoms could be triggered. The triggered attacks were phenotyped in the same way as spontaneous ones. Percentage agreement and Cohen’s kappa measure of agreement were used to identify concordance between patient-reported triggers and the corresponding spontaneous and triggered premonitory symptoms. Percentage agreement of > 60% and/or a kappa value > 0.3 with P < 0.05 were considered significant.ResultsThere was statistically significant agreement between perception of light as a migraine trigger and spontaneous premonitory photophobia; perception of sound as a trigger and triggered premonitory phonophobia; skipping meals as a trigger and spontaneous premonitory food cravings; and food triggers and spontaneous premonitory food cravings. There was good agreement between stress and premonitory triggered mood change.ConclusionsAt least some patient-reported triggers, such as light, sound, foods and skipping meals, may represent early brain manifestations of the premonitory phase of the migraine attack.

White matter anisotropy and response to cognitive behavior therapy for posttraumatic stress disorder

Trauma-focused cognitive behavior therapy (TF-CBT) is the gold standard treatment for posttraumatic stress disorder (PTSD), up to one-half of PTSD patients remain treatment non-responders. Although studies have used functional MRI to understand the neurobiology of treatment response, there is less understanding of the role of white matter brain structures in response to TF-CBT. Thirty-six treatment-seeking PTSD patients and 33 age-gender matched healthy controls completed diffusion-weighted imaging scans at baseline. Patients underwent nine sessions of TF-CBT treatment and PTSD symptom severity was assessed with the Clinician-Administered PTSD Scale before and after completing treatment. Patients were assessed to estimate the reduction in overall symptoms and also specifically fear and dysphoric symptoms of PTSD. Tract-based spatial statistical analyses were performed for the PTSD group to evaluate whole-brain correlations of fractional anisotropy (FA) with improvement in overall, fear, and dysphoric symptoms using non-parametric permutation inference testing (pFWE < 0.05). Next, we evaluated if these significant measures also characterized PTSD from controls. Greater improvement in dysphoric symptoms was found correlated with lower FA in white matter regions associated with the limbic system, frontal cortex, thalamic association and projection fibers, corpus callosum, and tracts related to the brainstem. White matter anisotropy was not found associated with either overall or fear symptoms. FA in the significant clusters was similar between PTSD and controls. White-matter related to key functional regions may also play an important role in response to TF-CBT. Our results underscore the heterogeneity of PTSD and the need to evaluate distinct symptom phenotypes in treatment studies.

Symptom heterogeneity and patient subgroup classification among US patients with post-treatment Lyme disease: an observational study

ObjectivesTo identify underlying subgroups with distinct symptom profiles, and to characterise and compare these subgroups across a range of demographic, clinical and psychosocial factors, within a heterogeneous group of patients...

Brain Injury in Critical Illness and a Note on the Virus

Brain Injury in Critical Illness and a Note on the Virus

Interaction of watermelon chlorotic stunt virus with satellites

Pumpkin (Cucurbita maxima) plants showing begomovirus-like yellowing, curling and stunting symptoms were observed in the Barka Governate, Oman in December 2016. Cloning and sequencing of rolling circle amplified circular DNA molecules showed the plants to be infected with watermelon chlorotic stunt virus (WmCSV); a bipartite Old World begomovirus that is a serious pathogen of cucurbit crops across the Middle East, Arabian Peninsula and North Africa. Although not known to interact with satellites, the risk of WmCSV possibly interacting with betasatellites and alphasatellites to agriculture in Oman, and beyond, was assessed. Tomato leaf curl betasatellite (ToLCB) and Ageratum enation alphasatellite (AEA) are commonly associated with other begomoviruses in Oman. A cognate pair of WmCSV DNA-A and DNA-B clones was highly infectious to Nicotiana benthamiana by Agrobacterium-mediated inoculation, inducing severe leaf curling and crumpling symptoms. Inoculation of only the DNA-A component with ToLCB or AEA did not result in symptoms or significant levels of the DNA-A or satellites in plants. Inoculation of both DNA-A and DNA-B with ToLCB or AEA resulted in a slight change in symptom phenotype and reduced DNA-A and DNA-B titers. Although ToLCB DNA levels in co-infected plants were low, the levels of AEA were high. This is the first identification of WmCSV infecting pumpkin in Oman and the isolates identified were typical of the virus previously identified in Oman, being distinct from the isolates occurring in the western Arabian Peninsula. Additionally the infectivity analyses suggest that WmCSV interaction with satellites, in contrast to some other bipartite begomoviruses, is unlikely to result in more serious disease in the field.

P.503 Positive symptom phenotypes appear progressively in "enhanced dopamine in prodromal schizophrenia", a new animal model of the schizophrenia prodrome

Multiple sclerosis (MS) is a common disease of the central nervous system and a major cause of disability amongst young adults. Genome-wide association studies have identified many novel susceptibility loci including rs2248359. We hypothesized that genotypes of this locus could increase the risk of MS by regulating expression of neighboring gene, CYP24A1 which encodes the enzyme responsible for initiating degradation of 1,25-dihydroxyvitamin D3.We investigated this hypothesis using paired gene expression and genotyping data from three independent datasets of neurologically healthy adults of European descent. The UK Brain Expression Consortium (UKBEC) consists of post-mortem samples across 10 brain regions originating from 134 individuals (1231 samples total). The North American Brain Expression Consortium (NABEC) consists of cerebellum and frontal cortex samples from 304 individuals (605 samples total). The brain dataset from Heinzen and colleagues consists of prefrontal cortex samples from 93 individuals. Additionally, we used gene network analysis to analyze UKBEC expression data to understand CYP24A1 function in human brain.The risk allele, rs2248359-C, is strongly associated with increased expression of CYP24A1 in frontal cortex (p-value=1.45×10−13), but not white matter. This association was replicated using data from NABEC (p-value=7.2×10−6) and Heinzen and colleagues (p-value=1.2×10−4). Network analysis shows a significant enrichment of terms related to immune response in eight out of the 10 brain regions.The known MS risk allele rs2248359-C increases CYP24A1 expression in human brain providing a genetic link between MS and vitamin D metabolism, and predicting that the physiologically active form of vitamin D3 is protective. Vitamin D3's involvement in MS may relate to its immunomodulatory functions in human brain.Medical Research Council UK; King Faisal Specialist Hospital and Research Centre, Saudi Arabia; Intramural Research Program of the National Institute on Aging, National Institutes of Health, USA.

Knowledge and Attitudes About Genetic Testing Among Black and White Women with Breast Cancer.

Prior to embarking on a large descriptive evaluation of genetic/racial variations in symptom phenotype, we sought foundational information to determine racial differences in (1) feasibility (consent) and acceptability of collecting genomic samples, (2) genetic literacy, and (3) concerns of genomic research during breast cancer (BC) chemotherapy. Women with early-stage BC undergoing chemotherapy were recruited from an academic, urban breast care center. Information was collected for consent to participate, genetic literacy, and concerns about genetic testing in Black and White women with BC. Fifty-six women were eligible, and 48 were consented (24 Black, 24 White). All participants consented to blood testing. This highly educated sample's mean age was 52.5+12.05 (years). Education (years) and genetic knowledge were positively correlated (p = .038). Genetic scores were high, and only one question significantly differed by race. On interview, most participants thought conducting genetic research helped to better understand hereditary disease and/or identify genes that cause disease and stated that they participated in the research to help other people. The majority of participants responded that friends/family would participate in genetic research without concerns, though three Black participants cited mistrust as a possible concern. Overall, there were high levels of genetic knowledge, slightly different between Black and White women. There were no high levels of personal concern regarding genetic testing. Black women reported more concern than White women that friends/family would have hesitations about participating in genetic research. There was general acceptability of blood collection for genetic testing among women with early-stage BC without racial difference.

4545 Identifying Symptom Pattern Trajectories among Heart Failure Patients in a Palliative Care Trial: A Work In Progress

OBJECTIVES/GOALS: This work-in-progress aims to: 1) identify and differentiate symptom pattern trajectories in a sample of older adult heart failure (HF) patients over 24 weeks, and 2) examine associations between sociodemographic/clinical/physiological characteristics, dyadic health, and symptom trajectories. METHODS/STUDY POPULATION: ENABLE CHF-PC, a palliative care RCT (NCT02505425), was conducted at a Southeastern US medical center. Between 2016-2018, 415 older adult HF patients and 159 family caregivers were randomized to receive a psychoeducational intervention or usual care. Baseline sociodemographic information (age, gender, rurality, etc.) were collected. Outcome variables of interest include symptoms (Kansas City Cardiomyopathy Questionnaire (KCCQ), Functional Assessment of Chronic Illness Therapy-Palliative 14, Hospital Anxiety and Depression Scale (HADS)) and dyadic health (PROMIS-SF Global Health). We have calculated baseline descriptive statistics. Future work includes latent growth mixture modeling to identify distinct symptom trajectories and univariate associations with patient level factors. RESULTS/ANTICIPATED RESULTS: Of 415 patient participants, mean age was 64, 53% were male; 55% were African American; 26% were rural dwellers; 46% had +15.8) and low anxiety (6.7+3.6) and depressive symptoms (5.7+4.3) on the HADS. Of 159 family caregivers participants, the mean age was 57.9, 85.4% were female, 51.9% were African-American, and 65.2% were the patient’s spouse/partner. DISCUSSION/SIGNIFICANCE OF IMPACT: Limited data describes HF symptom pattern trajectories.How co-occurring symptoms affect quality of life or are affected by personal or situational factors are not well-understood. This study will help to identify factors and symptom phenotypes that may serve as targets for future interventions.

4292 Epigenetic Age and Depressive Symptoms in African American Women with Cardiometabolic Conditions

OBJECTIVES/GOALS: To examine the relationship between epigenetic age acceleration (EAA) and depressive symptoms in a cohort of African American women (AAW) with cardiometabolic conditions (CMC) including hypertension, diabetes, obesity; and to explore clinical phenotypes of depressive symptoms in this population. METHODS/STUDY POPULATION: This secondary analysis utilized genomic and longitudinal clinical data from AAW in the InterGEN cohort (n = 250). EWAS data was used to estimate EAA based on the Horvath method, which incorporates the DNA methylation statuses at 353 specific CpG sites and regresses this epigenetic age on chronological age to determine EAA. Pearson’s correlations and linear regression will be used to examine the relationship between EAA and depressive symptoms and a linear mixed model will investigate this relationship over four time points during a two-year period. Clinical phenotyping of depressive symptoms will be explored using a cluster analysis. RESULTS/ANTICIPATED RESULTS: Analysis is underway and will be complete by the time of presentation. We hypothesize that higher EAA will associate with higher depressive symptoms and poorer trajectories over time. We expect that this relationship may be meditated by the presence of CMCs. Exploratory analysis of clinical phenotyping is expected to provide descriptive evidence with respect to specific depressive symptoms or clusters which are most associated with EAA and CMCs. These results will address several gaps. To our knowledge, this is the first study to examine the relationship of EAA and depressive symptoms considering the role of CMC, in a historically understudied population with disproportionate risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Depression limits life quality and quantity and is highly comorbid in CMC. AAW have high risk of comorbidity, and this study furthers knowledge of depression and aging with a clinically accessible marker and aids recognition of a heterogenous phenotype in an undertreated population.

The concurrent disturbance of dynamic functional and structural brain connectome in major depressive disorder: the prefronto-insular pathway

BackgroundRobust evidence has shown that abnormal function networks, particularly the salience network (SN), are observed in depressed patients. Although white matter structural connectivity may predict time-varying functional connectivity, including symptom phenotype, in psychiatric disorders, there is still a gap in elucidating the concurrent dynamic functional and structural connectivity profiles of the SN in depressed patients. MethodsWe measured static and dynamic functional connectivity (FC) of the SN using resting-state fMRI BOLD time series in 76 subjects (21 with major depressive disorder (MDD), 27 with bipolar depression (BD), and 28 healthy controls (HC)). Hamilton Depression Scale total score was used to measure depression severity. Furthermore, we investigated the concurrent structural connectivity using diffusion kurtosis imaging (DKI)-based tractography. ResultsOur findings suggested that in the presence of MDD, both structural and dynamic (but not static) FC were reduced in the SN, particularly affecting the left prefronto-insular pathways (L.aPFC-L.insula). MDD patients showed decreased connectivity variability within the SN compared with HC. The aberrant dynamic FC in the prefronto-insular pathways of the SN related to severity of depressive symptoms in MDD. Furthermore, compared with BD patients, those with MDD showed significantly decreased dynamic FC in the left prefronto-parietal system (L.aPFC-lateral parietal cortex). LimitationsThe generalizability of our findings is, to some extent, constrained by the small sample size. ConclusionsThe integrity of SN connectivity, particularly the prefronto-insular pathway, appears to be a crucial signature of MDD. The perturbed dynamic interaction of SN with prefrontal regions may underlie the clinical severity in depressed patients.

Prevalence estimates of mental health problems in children and adolescents with intellectual disability: A systematic review and meta-analysis

Children and adolescents with intellectual disability are at risk of developing psychiatric symptoms and disorders; yet, the estimates reported in the literature have been inconsistent, presenting a potential barrier for service planning and delivery. Sources of variability could arise from differences in measurement instruments as well as subgroup membership by severity of intellectual disability, gender and age. This systematic review aimed to address these gaps. MEDLINE and PsycINFO databases were searched from inception to 2018 and selected studies were reviewed. Studies were included if they reported point prevalence estimates of mental health symptomology or diagnoses in a general population of 6- to 21-year-old individuals with intellectual disability. The Joanna Briggs Institute Prevalence Critical Appraisal Checklist was applied to eligible papers to appraise their scientific strength. Pooled prevalence for mental health symptomology was determined using a random-effects meta-analysis. A total of 19 studies were included, including 6151 children and adolescents. The pooled prevalence estimate captured by the Developmental Behaviour Checklist was 38% (95% confidence interval = [31, 46]), contrasting with 49% (95% confidence interval = [46, 51]) captured by the Child Behaviour Checklist; both rates were higher than a non-intellectual disability population. Severity of intellectual disability did not significantly influence the Developmental Behaviour Checklist risks. Insufficient data were available to conduct statistical analyses on the effects of age, gender and socioeconomic status. Of diagnosed psychiatric disorders, attention deficit/hyperactivity disorder (30%), conduct disorder (3-21%) and anxiety disorders (7-34%) were the most prevalent conditions. This review consists of the largest sample hitherto evaluated. In the intellectual disability population, mental health comorbidities could be better detected by a symptom phenotype than a psychiatric diagnostic phenotype. Crucially, future research needs to address the effect of measurement validity in the intellectual disability population. Estimated prevalence rates were high compared to the general population, indicating the importance of systematic screening, case detection and appropriate management.

M168. CLINICAL-ANATOMICAL PHENOTYPES OF SCHIZOPHRENIA

BackgroundAlthough widespread structural brain abnormalities have been consistently reported in schizophrenia, their relation to the heterogeneous clinical manifestations is not well understood. Multivariate methods are needed to uncover covariance patterns between multiple symptom dimensions and system-wide brain imaging data.MethodsThis cross-sectional study used structural magnetic resonance imaging and neuropsychological data from 133 patients with chronic schizophrenia (48 female, 34.8±13.2 years) from the Northwestern University Schizophrenia Data and Software Tool (NUSDAST). We estimate disease-related voxel-wise tissue volume loss using deformation-based morphometry (DBM) of T1 weighted images. In patients with schizophrenia, multiple clinical dimensions including positive/negative symptoms and cognitive deficits, demographic data as well as individual tissue volume loss (DBM) were included in the multivariate model. Clinical-anatomical phenotypes were identified using partial least squares analysis.ResultsMultivariate analysis revealed three distinct clinical-anatomical phenotypes accounting for 27.5%, 15%, and 13% of the shared covariance between clinical-behavioural data and tissue volume loss (total of 55.5%). The first clinical-anatomical phenotype encompassed cognitive impairments, severity of negative symptoms and tissue volume loss within the default mode network and visual network. The second clinical-anatomical phenotype was associated with additional cognitive impairments and tissue volume loss within the frontoparietal and ventral attention network, while the third clinical-anatomical phenotype encompassed a mixed positive and negative symptoms phenotype and tissue volume loss within the dorsal attention network. Critically, the pattern of volume loss within the first most prevalent clinical-anatomical phenotype mediated (a*b) the effect of socioeconomic status on clinical outcome (cognitive performance and negative symptoms) (a*b=-0.033(0.008); P<1.0×〖10〗^(-4); 95% CI [-0.049, -0.018]). Finally, we partly replicated the first clinical-anatomical phenotype in an independent sample of patients with schizophrenia (n=108).DiscussionThe heterogeneous clinical manifestation of schizophrenia can be significantly explained by three clinical-anatomical phenotypes. Despite their distributed topography, each phenotype is centered on a specific, well-defined set of intrinsic networks.

Delirium Severity Trajectories and Outcomes in ICU Patients. Defining a Dynamic Symptom Phenotype.

Rationale: Delirium severity and duration are independently associated with higher mortality and morbidity. No studies to date have described a delirium trajectory by integrating both severity and duration.Objectives: The primary aim was to develop delirium trajectories by integrating symptom severity and duration. The secondary aim was to investigate the association among trajectory membership, clinical characteristics, and 30-day mortality.Methods: A secondary analysis of the PMD (Pharmacologic Management of Delirium) randomized control trial (ClinicalTrials.gov Identifier: NCT00842608; N = 531) was conducted. The presence of delirium and symptom severity were measured at least daily for 7 days using the Confusion Assessment Method for the intensive care unit (CAM-ICU) and CAM-ICU-7 (on a scale of 0-7, with 7 being the most severe). Delirium trajectories were defined using an innovative, data-driven statistical method (group-based trajectory modeling [GBTM]) and SAS v9.4.Results: A total of 531 delirious participants (mean age 60 yr [standard deviation = 16], 55% female, and 46% African American) were analyzed. Five distinct delirium trajectories were described (CAM-ICU-7: mean [standard deviation]); mild-brief (CAM-ICU-7: 0.5 [0.5]), severe-rapid recovers (CAM-ICU-7: 2.1 [1.0]), mild-accelerating (CAM-ICU-7: 2.2 [0.9]), severe-slow recovers (CAM-ICU-7: 3.9 [0.9]), and severe-nonrecovers (CAM-ICU-7: 5.9 [1.0]). Baseline cognition and race were associated with trajectory membership. Trajectory membership independently predicted 30-day mortality while controlling for age, sex, race, cognition, illness severity, and comorbidities.Conclusions: This secondary analysis described five distinct delirium trajectories based on delirium symptom severity and duration using group-based trajectory modeling. Trajectory membership predicted 30-day mortality.

Differences in the Clinical Characteristics of Persistent Idiopathic Facial Pain (Atypical Odontalgia) Patients with or Without Neurovascular Compression of the Trigeminal Nerve.

BackgroundPersistent idiopathic facial pain (PIFP) is the unexplained pain along the territory of the trigeminal nerve, including nonorganic tooth pain called atypical odontalgia (AO). Though PIFP is debilitating to patients’ livelihood and well-being, its pathophysiology remains poorly understood. Although neurovascular compression (NVC) of the trigeminal nerve is known to be associated with trigeminal neuralgia (TN), the relationship between NVC and other orofacial pains has not been fully elucidated.MethodsIn this study, we investigated the differences in the characteristics of PIFP (primarily AO) patients in the presence or absence of NVC. A retrospective analysis was performed on data from 121 consecutive patients who had been diagnosed with unilateral PIFP according to the criteria of the International Classification of Headache Disorders (ICHD)–3 and underwent magnetic resonance imaging scans of the head.ResultsIn the group without NVC, characteristic findings were significant for psychiatric morbidity, somatization, and pain disability, when compared with the group with NVC. Furthermore, the group without NVC exhibited significant headache, noncardiac chest pain, shortness of breath, and pain catastrophizing.ConclusionsThese results suggest that PIFP patients can be divided into two groups: one consistent with a neuropathic pain phenotype when NVC is present and a functional somatic symptom phenotype when presenting without NVC. Our findings may enable a more precise understanding of pathophysiology of PIFP and lead to better treatment strategies.

The relationship between diurnal variation of cytokines and symptom expression in mild obstructive sleep apnea.

To identify the relationship between (1) cytokines and everyday symptoms and (2) cytokine diurnal variation and everyday symptoms in mild obstructive sleep apnea (OSA). An observational, single-night study of 20 adults with mild to moderate OSA undergoing diagnostic polysomnography. Everyday symptoms included sleepiness measured by Stanford Sleepiness Scale, fatigue and energy levels measured by Lee Fatigue Scale, and cytokine plasma concentrations including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α (TNF-α) measured concurrent with symptoms at presleep (8 pm to 10 pm; time 1) and postsleep (5 am to 6 am; time. 2) Cytokine diurnal variation was calculated as [time 2 - time 1]. Wilcoxon signed-rank tests and Spearman partial rank correlations adjusted for age, body mass index, cardiovascular disease, and type 2 diabetes were used. Twenty patients (50% male, obese, median age = 51.0 years) with mild OSA (apnea-hypopnea index, AHI; median 9.5 events/h) were evaluated. Evening IL-6 was associated with evening symptoms, including sleepiness (r = .69, P = .002) and energy level (r = -0.68, P = .003); morning IL-8 (r = .73, P = .001), and TNF-α (r = .59, P = .015) were associated with morning fatigue. Only morning IL-8 (r = -0.57, P = .022) and diurnal variations in IL-8 (r = -0.60, P = .014) were associated with morning energy level. There is scant evidence addressing the diurnal variation of inflammatory biomarkers and the relationship with symptom expression in mild OSA. The present findings provide preliminary mechanistic findings for symptom expression in OSA and contribute insight to mild OSA symptom phenotypes.

Clinical Profile of Non-Motor Symptoms in Patients with Essential Tremor: Impact on Quality of Life and Age-Related Differences.

BackgroundIdentifying the clinical phenotypes of non-motor symptoms (NMSs) of essential tremor (ET) among different populations is necessary due to their impact on the quality of life (QoL). This study aimed to investigate the clinical phenotype and impact of NMSs on QoL in Egyptian patients with ET.MethodsThirty ET patients were compared to 30 matched controls. Subjects were evaluated by the Fahn-Tolosa-Marin Tremor Rating Scale, Non-Motor Symptoms Scale (NMSS), Montreal Cognitive Assessment, Hamilton Anxiety Rating Scale, Beck Depression Inventory, Pittsburgh Sleep quality Index, and the Short Form 36 Health Survey Questionnaire. Both groups were divided into two subgroups of younger (<45 years, 14 patients) and older age (>45 years, 16 patients) groups, to investigate age-related differences.ResultsET patients showed significantly worse cognition, depression, anxiety, sleep and NMSS domains (p < 0.001), compared to controls, that negatively affected and predicted QoL. Older patients had more cognitive impairment (p = 0.003) and worse sleep/fatigue (p = 0.032) and sexual functions (p = 0.006), compared to younger group.DiscussionThe study supports that NMSs are integral part of ET, negatively affect QoL, and similarly affect younger and older patients. Therefore, NMSs should be explored for proper care of ET patients.

Consortium Building for Nurse Scientists Interested in Symptoms Research in the Era of Precision Health.

This article aims to provide perspectives on the establishment of a consortium for nurse scientists with similar career trajectories interested in cancer-related symptoms (CRS) research. Hereby, we describe the development of and recent outcomes from the CRS consortium, the lessons learned in establishing the consortium, and future directions to advance the science of CRS. New and innovative strategies are needed to address the complexity of CRS research. A CRS consortium was created to allow a mechanism for oncology nurse scientists with varying expertise to collaborate to advance CRS research. The National Institutes of Health (NIH) Symptom Science Model (SSM) guides the research of the CRS Consortium. A need for improved CRS assessment and management has been identified. The CRS consortium was created as a collaborative think tank to begin to address this need. Guided by the NIH SSM, CRS consortium members have worked to define symptom phenotypes, enhance understanding of the biologic mechanisms that can contribute to symptom phenotypes, and develop tailored interventions to improve symptom management. Dissemination of the CRS consortium efforts involve publications and presentations. Nurse scientists interested in symptom science and biobehavorial research face many challenges on how to initiate and sustain independent programs of research. Through the formation of a CRS consortium, oncology nurse scientists can work together to address identified issues in symptom measurement and management.

Ruxolitinib, a JAK1/JAK2 Selective Inhibitor, Ameliorates Gastrointestinal and Cutaneous Pathogenesis in MHC-Mismatched Preclinical Models of Acute and Chronic Graft-Versus-Host Disease

Background: Allogeneic hematopoietic cell transplantation (alloHCT) is potentially curative for a variety of hematologic malignancies. However, rather than targeting tumor cells, alloreactive donor T cells may attack healthy recipient tissue triggering graft-versus-host disease (GVHD) resulting in morbidity and mortality. Acute GVHD (aGVHD) clinically presents with gastrointestinal (GI) pathology and is primarily T cell mediated. In contrast, chronic GVHD commonly demonstrates skin inflammation and fibrosis with an autoimmune-like phenotype. Pharmacological inhibition of JAK/STAT signaling has the potential to regulate aberrant immune cell functions involved in the pathogenesis of acute and chronic GVHD. Aim: Characterize the effectiveness of ruxolitinib to modulate in vitro and in vivo immunological mechanisms that are described to be critical in acute and chronic GVHD pathogenesis. Materials and Methods: MHC-mismatch aGVHD was induced in recipient BALB/c mice receiving C57BL/6 donor transplant. Sclerodermatous cGVHD was induced in C57BL/6 mice using LP/J strain donor splenocytes and bone marrow cells. Ruxolitinib or vehicle was orally administered twice daily. Efficacy was assessed by GVHD symptom scores, cachexia, and histological analysis of end organ damage. Mixed lymphocyte reactions (MLR) were cultured for five days in the presence of ruxolitinib for changes in activation markers and cytokine release. Results: Ruxolitinib treatment ameliorated daily aGVHD severity scores with concomitant reduction of GI tract infiltration and tissue damage. Overall aGVHD mice survival was significantly improved with JAK1/2 inhibition. Therapeutic ruxolitinib treatment initiated after cGVHD symptom onset significantly inhibited the chronic-progressive symptom phenotype and reduced tissue markers of inflammation and fibrosis. Ruxolitinib demonstrated concentration-dependent inhibition of activated T cells and reduced JAK-STAT signaling cytokines considered relevant in GVHD inflammation. Conclusion: Ruxolitinib, a potent and selective JAK1/2 inhibitor, significantly ameliorated pro-inflammatory pathways in vitro and in vivo which are thought to be highly relevant for acute and chronic GVHD pathogenesis. On May 24, 2019, the FDA approved ruxolitinib for steroid-refractory acute graft-versus-host disease (aGVHD) in adult and pediatric patients 12 years and older. Ruxolitinib is currently being evaluated in clinical trial (REACH3: NCT03112603) for patients with steroid-refractory cGVHD. Disclosures Huarte: Incyte corporation: Employment, Equity Ownership. Parker:Incyte corporation: Employment, Equity Ownership. Juvekar:Incyte corporation: Employment, Equity Ownership. Oliver:Incyte corporation: Employment, Equity Ownership. Yao:Incyte corporation: Employment, Equity Ownership. Smith:Incyte corporation: Employment, Equity Ownership.

Symptom network topological features predict the effectiveness of herbal treatment for pediatric cough.

Pediatric cough is a heterogeneous condition in terms of symptoms and the underlying disease mechanisms. Symptom phenotypes hold complicated interactions between each other to form an intricate network structure. This study aims to investigate whether the network structure of pediatric cough symptoms is associated with the prognosis and outcome of patients. A total of 384 cases were derived from the electronic medical records of a highly experienced traditional Chinese medicine (TCM) physician. The data were divided into two groups according to the therapeutic effect, namely, an invalid group (group A with 40 cases of poor efficacy) and a valid group (group B with 344 cases of good efficacy). Several well-established analysis methods, namely, statistical test, correlation analysis, and complex network analysis, were used to analyze the data. This study reports that symptom networks of patients with pediatric cough are related to the effectiveness of treatment: a dense network of symptoms is associated with great difficulty in treatment. Interventions with the most different symptoms in the symptom network may have improved therapeutic effects.