Titer and Distribution of Candidatus Phytoplasma pruni in Prunus avium

‘Candidatus Phytoplasma pruni’ infection in cherries causes small, misshapen fruit with poor color and taste, rendering the fruit unmarketable. However, this is a disease with a long development cycle and a scattered, non-uniform symptom distribution in the early stages. To better understand the biology as well as the relationship between pathogen titer and disease expression, we carried out seasonal, spatial, and temporal examinations of ‘Ca. P. pruni’ titer and distribution in infected orchard-grown trees. Sequential sampling of heavily infected trees revealed marked seasonal patterns, with differential accumulation in woody stem and leaf tissues, and most notably within fruit in the early stages of development from bloom to pit hardening. Furthermore, mapping phytoplasma distribution and titer in trees at different stages of infection indicated that infection proceeds through a series of stages. Initially, infection spreads basipetally and accumulates in the roots before populating aerial parts of the trees from the trunk upwards, with infection of specific tissues and limbs followed by an increasing phytoplasma titer. Finally, we observed a correlation between phytoplasma titer and symptom severity, with severe symptom onset associated with 3-4 orders of magnitude more phytoplasma than mild symptoms. Cumulatively, these data aid in accurate sampling and management decision making and furthers our understanding of disease development.

Evaluating Real-World COVID-19 Vaccine Effectiveness Using a Test-Negative Case-Control Design

It is important to assess the extent to which the real-world effectiveness of marketed vaccines is consistent with that observed in the clinical trials, and to characterize how well vaccines prevent COVID-19 symptoms. We conducted a modified test-negative design (TND) to evaluate the RW effectiveness of three COVID-19 vaccines by leveraging data from an on-going, US community-based registry. Vaccine effectiveness was examined in two ways: considering cases who (1) tested positive for COVID-19 (695 cases, 1,786 controls) and who (2) tested positive with at least one moderate/severe COVID-19 symptom (165 cases, 2,316 controls). Any vaccination (full or partial) was associated with a 95% reduction in the odds of having a positive COVID-19 test [adjusted odds ratio (aOR) = 0.05 (95% confidence interval (CI): 0.04, 0.06)]. Full vaccination was associated with an aOR of 0.03 (95% CI: 0.03, 0.05) while partial vaccination had an aOR of 0.08 (95% CI: 0.06, 0.12). Any vaccination was associated with a 71% reduction in the odds of testing positive and having at least one moderate/severe symptom (aOR=0.29 (95% CI: 0.20, 0.40)). High effectiveness was observed across all three vaccine manufacturers both for prevention of positive COVID-19 test results and prevention of moderate/severe COVID-19 symptoms.

Receptivity to a Nurse-Led Symptom Management Intervention Among Highly Symptomatic Patients With Cancer

Background The symptom burden associated with cancer and its treatment can negatively affect patients’ quality of life and survival. Symptom-focused collaborative care model (CCM) interventions can improve outcomes, but only if patients engage with them. We assessed the receptivity of severely symptomatic oncology patients to a remote nurse-led CCM intervention. Methods In a pragmatic, cluster-randomized, stepped-wedge trial conducted as part of the National Cancer Institute IMPACT Consortium (E2C2, NCT03892967), patients receiving cancer care were asked to rate their sleep disturbance, pain, anxiety, emotional distress, fatigue, and limitations in physical function. Patients reporting at least 1 severe symptom (≥7/10) were offered phone consultation with a nurse symptom care manager (RN SCM). Initially, patients had to “opt-in” to receive a call, but the protocol was later modified so they had to “opt-out” if they did not want a call. We assessed the impact of opt-in vs opt-out framing and patient characteristics on receptiveness to RN SCM calls. All statistical tests were 2-sided. Results Of the 1204 symptom assessments (from 864 patients) on which at least 1 severe symptom was documented, 469 (39.0%) indicated receptivity to an RN SCM phone call. The opt-out period (odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.12 to 2.32, P = .01), receiving care at a tertiary care center (OR = 3.59, 95% CI = 2.18 to 5.91, P < .001), and having severe pain (OR = 1.80, 95% CI = 1.24 to 2.62, P = .002) were associated with statistically significantly greater willingness to receive a call. Conclusions Many severely symptomatic patients were not receptive to an RN SCM phone call. Better understanding of reasons for refusal and strategies for improving patient receptivity are needed.

Characterizing the heterogeneous course of inattention and hyperactivity-impulsivity from childhood to young adulthood

To advance understanding of the heterogeneity in the course of ADHD, joint symptom trajectories of inattention and hyperactivity-impulsivity from childhood to young adulthood were modelled and associated with genetic, demographic, and clinical characteristics. Data were obtained from the NeuroIMAGE cohort which includes 485 individuals with ADHD, their 665 siblings, and 399 typically developing children. Trajectories were based on scores of the Conners Parent Rating Scale Revised and estimated over seven homogeneous age bins (from 5 to 28 years) using parallel process latent class growth analysis on data collected across 2–4 time points. Multilevel multinomial logistic regression was used to identify characteristics that differentiated between the derived classes. A seven-class solution revealed “severe combined stable” (4.8%), “severe combined decreasing” (13%), “severe inattentive stable” (4.8%), “moderate combined increasing” (7.5%), “moderate combined decreasing” (12.7%), “stable mild” (12.9%), and “stable low” (44.3%) classes. Polygenic risk for depression, ADHD diagnosis, ADHD medication use, IQ, comorbid symptom levels (foremost oppositional behaviour), and functional impairment levels differentiated classes with similar ADHD symptom levels in childhood but a diverging course thereafter. The course of ADHD is highly heterogeneous, with stable, decreasing, and increasing trajectories. Overall, severe symptom levels in childhood are associated with elevated-to-severe symptom levels in adolescence and young adulthood, despite substantial symptom reductions. Beyond symptom severity in childhood, genetic, demographic, and clinical characteristics distinguish the heterogeneous course.

Attachment to Pets Moderates Transitions in Latent Patterns of Mental Health Following the Onset of the COVID-19 Pandemic: Results of a Survey of U.S. Adults

This cross-sectional study examined whether, and to what extent, attachment to pets was associated with changes in latent patterns of adults’ perceived mental health symptoms during the COVID-19 pandemic (n = 1942). We used latent transition analysis to determine the stability of subgroup membership pre- and post-COVID and the effect of attachment to pets on transition probabilities. Mental health before COVID-19 was measured retrospectively. Five subgroups were identified: low symptoms, mild symptoms, moderate symptoms, high symptoms, and severe symptoms. Among individuals in the moderate and high symptoms subgroups, those who reported high attachment to pets generally had greater odds of transitioning to a less severe symptom profile (OR = 2.12) over time than those with low attachment to pets (OR = 1.39). However, those who had a severe symptom profile and high attachment to pets had lower odds of transitioning to a less severe symptom profile (OR = 0.30) and higher odds of maintaining a severe symptom profile (OR = 3.33) than those with low attachment to pets. These findings suggest that the protective and risk effects of attachment to pets differ based on individuals’ psychological symptom patterns across multiple indicators. We discuss the implications of these findings for research, policy, and practice.

Lysophosphatidic Acid-Activated Calcium Signaling Is Elevated in Red Cells from Sickle Cell Disease Patients

(1) Background: It is known that sickle cells contain a higher amount of Ca2+ compared to healthy red blood cells (RBCs). The increased Ca2+ is associated with the most severe symptom of sickle cell disease (SCD), the vaso-occlusive crisis (VOC). The Ca2+ entry pathway received the name of Psickle but its molecular identity remains only partly resolved. We aimed to map the involved Ca2+ signaling to provide putative pharmacological targets for treatment. (2) Methods: The main technique applied was Ca2+ imaging of RBCs from healthy donors, SCD patients and a number of transgenic mouse models in comparison to wild-type mice. Life-cell Ca2+ imaging was applied to monitor responses to pharmacological targeting of the elements of signaling cascades. Infection as a trigger of VOC was imitated by stimulation of RBCs with lysophosphatidic acid (LPA). These measurements were complemented with biochemical assays. (3) Results: Ca2+ entry into SCD RBCs in response to LPA stimulation exceeded that of healthy donors. LPA receptor 4 levels were increased in SCD RBCs. Their activation was followed by the activation of Gi protein, which in turn triggered opening of TRPC6 and CaV2.1 channels via a protein kinase Cα and a MAP kinase pathway, respectively. (4) Conclusions: We found a new Ca2+ signaling cascade that is increased in SCD patients and identified new pharmacological targets that might be promising in addressing the most severe symptom of SCD, the VOC.

Circulating immunocytes and complements are correlated with severity of ischemic stroke

Background Immune factors are found to be involved in the pathophysiological process of ischemic stroke. However, the clinical role of the immune system in stroke remains unclear. Our study was designed to investigate the correlation between immunocytes (T cell, B cell, NK cell), complements and stroke severity. Methods 236 patients with first-ever ischemic stroke were included in our study and divided to mild, moderate and severe groups according to NHISS score at stroke onset. Modified Rankin Scale (mRS) was used to assess short-term prognosis 3 months after stroke. We also collected clinical data and test circulating T cells, CD8 + T cells, CD4 + T cells, B cells, NK cells, C3, C4, complement factor B (CFB) of each patient. Results We found NK cell(p = 0. 015), CFB (p = 0. 007), C3 (p = 0. 035) were significantly elevated in groups with higher NHISS score. CD4 + T cell (p = 0. 009), T cell (p = 0. 001) were decreased in groups with higher NHISS score. In multivariate logistic regression, CFB and C3 were independently associated with severity of stroke. CD4 + T cell, NK cell, T cell were independently associated with severe ischemic stroke. NK cell (p = 0.049), CFB (p = 0.035), C4 (p = 0.028) are were significantly higher in groups with higher mRS score. In binary analyses, CFB (p = 0.009, OR: 1.056, 95%CI: 1.014–1.099), C4 (p = 0.011, OR: 134.444, 95%CI: 3.115-5803.504) were independently associated with prognosis at 3 months after stroke adjusting onset. Conclusions Elevated circulating CFB was correlated with both severe symptom at stroke onset and worse prognosis. It indicates that CFB may be a predictor of stroke severity and prognosis. Reduced T cell counts, elevated C3 and NK cell were associated with severe symptom at stroke onset. C4 was associated with short-term prognosis.

SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe

People with pre-existing chronic health conditions are reportedly at high risk of getting the coronavirus disease (COVID-19) and of having a severe disease course but little data exist on rare diseases such as Primary Ciliary Dyskinesia (PCD). We studied risk and severity of SARS-CoV-2 infections among people with PCD using data from the COVID-PCD, a participatory study that collects data in real-time directly from people with PCD. Data was collected using online questionnaires. A baseline questionnaire collected information on demographic data, information about the PCD diagnosis and severity. A short weekly questionnaire collected information about current symptoms and incident SARS-CoV-2 infections. 578 people participated in the COVID-PCD by December 7, 2020, with a median number of follow-up weeks of 9 (interquartile range: 4-19 weeks). 256 (45%) of the participants had been tested for SARS-CoV-2 and 12 tested positive prior to study entry or during study follow up (2.1% of the total included population, 95% confidence interval (CI) 1.1-3.6%). 4 people tested positive during the study follow-up, corresponding to an incidence rate of 2.5 per 100 person-years (95% CI: 0.9-6.5). Overall, reported severity was mild with two reporting no symptoms, eight reporting mild symptoms, one reporting severe symptom without hospitalisation, and one reporting hospitalisation for 9 days. The study suggests that with careful personal protection, people with PCD do not seem to have an increased risk of infection with SARS-COV-2, nor an especially severe disease course.Take home messageIn this longitudinal study of people with PCD followed weekly via online questionnaires, the incidence rate of COVID-19 and the proportion of participants infected were low, and the observed severity mostly mild.

Model-Based Patterns of Lymphedema Symptomatology: Phenotypic and Biomarker Characterization

Purpose of the Study More than 50% of breast cancer survivors without a diagnosis of lymphedema suffer daily from numerous and co-occurring lymphedema symptoms. This study aimed to identify lymphedema symptom patterns and the association of such patterns with phenotypic characteristics and biomarkers using latent class analysis (LCA). A prospective, descriptive, and repeated-measure design was used to enroll 140 women and collect data. Recent Findings LCA identified three distinct lymphedema symptom classes at 8 weeks and 12 months post-surgery: low, moderate, and severe symptom classes and associated phenotypic characteristics. Participants were more likely to be in the severe symptom classes at 12 months post-surgery if they had lower education level, cording, an axillary syndrome at 8 weeks post-surgery, neoadjuvant chemotherapy, and radiation. Summary Pre-surgery level of IL1-a, IL-6, IL-8, and VEGF was associated with the severe symptom class at 8 weeks post-surgery, suggesting that such biomarkers may be used to predict risk for lymphedema symptoms.

Self-reported overall wellbeing (OWb), physical function (PFn), and PRO-CTCAE symptom scores in post-operative and chemotherapy patients.

2064 Background: A standardized, validated tool for capturing symptoms from cancer patients, PRO-CTCAE, has been used to reduce symptom burden, decrease acute care needs, and preserve quality of life. The association between specific PRO-CTCAE symptom scores and single item measures of OWb and PFn were characterized to understand symptom constellations. Methods: A novel Epic-based symptom management program (eSyM) was deployed for GI, GYN, and thoracic cancer patients starting chemotherapy (Memphis Baptist) or having surgery (WVU Medicine). Patients received automated prompts to complete surveys via the patient portal (MyChart) on a fixed schedule, approximately twice/week. Each survey included one OWb item, one PFn item, and at least 6 PRO-CTCAE items (pain, nausea, vomiting, fatigue, anxiety, insomnia). The OWb and PFn items, which were created de novo, included 5 ordinal response options with corresponding pictograms (emojis from very happy to very sad for OWb; a figure walking to one prone in bed for PFn). Composite scores were generated: 0 for no symptoms, 1-2 for mild/moderate symptoms, and 3 for severe symptoms. We describe OWb and PFn and analyze associations between these items and PRO-CTCAE symptom scores. Results: Between 9/10/19-1/22/20, we collected 908 eSyM responses from 166 chemotherapy patients at Baptist (Age, M = 65), and 480 eSyM responses from 97 postoperative patients at WVU (Age, M = 57). The OWb and PFn scores demonstrated moderate correlation with PRO-CTCAE symptom scores (Baptist r = 0.63; WVU r = 0.75), and moderate correlation with mean symptom scores among surgery patients at WVU (r = 0.74); but lower correlation among chemotherapy patients at Baptist (r = 0.53-0.55). Scores improved over time following surgery, but not after initiation of chemotherapy. Among the 730 eSyM responses with none/mild values for both OWb and PFn (52.9% of all responses), only 4.5% reported any severe symptom; among 651 responses with impairment of OWb and/or PFn, 45.2% reported at least one severe symptom. Conclusions: Integration of eSyM into the Epic EHR enabled tracking of OWb, PFn, and PRO-CTCAE items. When asked alongside PRO-CTCAE symptom items, two single item OWb and PFn measures provided distinct information and correlated with symptom burden. These results demonstrate the feasibility of integrating ePRO collection into routine post-operative and medical oncology care and that PRO-CTCAE items provide information that is distinct from that obtained from global metrics of well-being. Clinical trial information: NCT03850912.