Improving multimodal physical function in adults with heterogeneous chronic pain; Protocol for a multisite feasibility RCT.

BACKGROUND: Chronic pain is associated with substantial impairment in physical function, which has been identified as a top concern among persons with pain. GetActive-Fitbit, a mind-body activity program, is feasible, acceptable, and associated with improvement in physical function among primarily White, sedentary individuals with pain. In preparation for a multisite efficacy trial, we must examine feasibility across multiple sites with diverse patient populations. Here we describe the protocol of a multisite, feasibility RCT comparing GetActive-Fitbit with a time- and attention-matched educational comparison (Healthy Living for Pain). We aim to 1) test multisite fidelity of clinician training; 2) evaluate multisite feasibility benchmarks, including recruitment of chronic pain patients taking <5000 steps/day and racial and ethnic minorities; and 3) optimize fidelity and study protocol in preparation for a future multisite efficacy trial. METHODS: Clinician training fidelity was assessed via roleplays and mock group sessions. Feasibility (i.e., recruitment, acceptability, credibility, adherence, satisfaction), multimodal physical function (e.g., self-report, 6-Minute Walk Test, step-count), and other psychosocial outcomes are assessed at baseline, posttest, and 6 months. Protocol optimization will be assessed using exit interviews and cross-site meetings. RESULTS: The trial is ongoing. Clinician training is complete. 87 participants have been recruited. 54 completed baseline assessments and randomization, 44 are mid-intervention, and 9 have completed the intervention and posttest. CONCLUSIONS: This study addresses the critical need for feasible, acceptable mind-body-activity interventions for chronic pain that follow evidence-based guidelines and improve all aspects of physical function across diverse populations. Results will inform a future fully-powered multisite efficacy trial. CLINICAL TRIAL REGISTRATION: NCT05700383.

Mindfulness, coping, and optimism as mechanisms of change in the 3RP-NF intervention.

INTRODUCTION: Neurofibromatosis (NF) is chronic neurogenetic condition that increases risk for poor quality of life, depression, and anxiety. Given the lack of biomedical treatments, we developed the "Relaxation Response Resiliency for NF" (3RP-NF) program to improve psychosocial outcomes among adults with NF. OBJECTIVE: To move toward effectiveness testing, we must understand mechanisms that explained treatment effects. We tested whether our hypothesized mechanisms of change-mindfulness, coping, and optimism-mediated improvements in quality of life, depression, and anxiety among adults in the 3RP-NF program (N = 114; ages 18-70; 72.80% female; 81.58% White). METHODS: We conducted mixed-effects models to assess whether these mechanisms uniquely mediated outcomes. RESULTS: Improvements in quality of life were most explained by coping, (b = 0.97, SE = 0.28, CI [0.45, 1.56]), followed by mindfulness (b = 0.46, SE = 0.17, CI [0.15, 0.82]) and optimism (b = 0.39, SE = 0.12, CI [0.17, 0.65]). Improvements in depression and anxiety were most explained by mindfulness (b = -1.52, SE = 0.38, CI [-2.32, -0.85], CSIE = -0.26; b = -1.29, SE = 0.35, CI [-2.04, -0.67], CSIE = -0.23), followed by optimism (b = 0.39, SE = 0.12, CI [0.17, 0.65]; b = -0.49, SE = 0.20, CI [-0.91, -0.13]), but were not explained by coping (b = 0.22, SE = 0.43, CI [-0.62, 1.07]; b = 0.06, SE = 0.46, CI [-0.84, 0.97]), respectively. CONCLUSIONS: Targeting mindfulness, coping, and optimism in psychosocial interventions may be a promising way to improve the lives of adults with NF.

Perceived discrimination and problematic opioid use among Black individuals with chronic musculoskeletal pain.

OBJECTIVE: Chronic musculoskeletal pain (CMP) is prevalent, burdensome, and associated with an increased risk for opioid use disorder. Evidence suggests that perceived racial/ethnic discrimination is associated with problematic substance use among Black individuals, but studies have not focused on problematic opioid use among Black individuals with CMP specifically or explored the contribution of perceived discrimination, pain intensity, and pain-relevant psychological factors to this association. METHOD: We recruited 401 Black individuals (Mage = 35.98, 51.9% female) with self-reported CMP and prescription opioid use. We tested whether perceived discrimination (a) was associated with self-reported problematic opioid use and (b) explained unique variance in this outcome after accounting for pain intensity, demographic factors, and psychological factors previously implicated in problematic opioid/substance use (distress tolerance and pain avoidance). RESULTS: Hierarchical linear regression analysis revealed that our model as a whole explained significant variance in problematic opioid use, R² = .30, F(6, 394) = 28.66, p < .001. Perceived discrimination specifically was associated with more problematic opioid use (ß = .39, SE = .05, p < .001) and explained unique variance in this outcome even after accounting for pain intensity (ß = .06, SE = .04, p = .20), distress tolerance (ß = -.10, SE = .05, p = .04), pain avoidance (ß = .12, SE = .05, p = .02), age (ß = -.10, SE = .05, p < .05), and employment status (ß = .13, SE = .11, p < .01). CONCLUSIONS: Systemic efforts to combat racism along with individualized therapeutic approaches to process and cope with perceived racial discrimination may be particularly important to prevent and reduce problematic opioid use among Black individuals with CMP. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Improving Health for Older Adults With Pain Through Engagement: Protocol for Tailoring and Open Pilot Testing of a Mind-Body Activity Program Delivered Within Shared Medical Visits in an Underserved Community Clinic.

BACKGROUND: Chronic musculoskeletal pain is prevalent and disabling among older adults in underserved communities. Psychosocial pain management is more effective than pharmacological treatment in older adults. However, underserved community clinics often lack psychosocial treatments, in part because of a lack of trained providers. Shared medical appointments, in which patients undergo brief medical evaluation, monitoring, counseling, and group support, are an efficacious and cost-effective method for chronic disease management in underserved clinics, reducing the need for specialized providers. However, shared medical visits are often ineffective for chronic pain, possibly owing to lack of inclusion of skills most relevant for older adults (eg, pacing to increase engagement in daily activities). OBJECTIVE: We have described the protocol for the development and initial pilot effectiveness testing of the GetActive+ mind-body activity intervention for older adults with chronic pain. GetActive+ was adapted from GetActive, an evidence-based intervention that improved pain outcomes among mostly affluent White adults. We aim to establish the initial feasibility, acceptability, fidelity, and effectiveness of GetActive+ when delivered as part of shared medical appointments in a community clinic. METHODS: We conducted qualitative focus groups and individual interviews with providers (n=25) and English-speaking older adults (aged ≥55 y; n=18) with chronic pain to understand the pain experience in this population, perceptions about intervention content, and barriers to and facilitators of intervention participation and implementation in this setting. Qualitative interviews with Spanish-speaking older adults are in progress and will inform a future open pilot of the intervention in Spanish. We are currently conducting an open pilot study with exit interviews in English (n=30 individuals in total). Primary outcomes are feasibility (≥75% of patients who are approached agree to participate), acceptability (≥75% of patients who enrolled complete 8 out of 10 sessions; qualitative), and fidelity (≥75% of session components are delivered as intended). Secondary outcomes include physical function-self-reported, performance based (6-minute walk test), and objective (step count)-and emotional function (depression and anxiety). Other assessments include putative mechanisms (eg, mindfulness and pain catastrophizing). RESULTS: We began enrolling participants for the qualitative phase in November 2022 and the open pilot phase in May 2023. We completed the qualitative phase with providers and English-speaking patients, and the results are being analyzed using a hybrid, inductive-deductive approach. We conducted rapid analysis of these data to develop GetActive+ before the open pilot in English, including increasing readability and clarity of language, reducing the number of skills taught to increase time for individual check-ins and group participation, and increasing experiential exercises for skill uptake. CONCLUSIONS: We provide a blueprint for the refinement of a mind-body activity intervention for older adults with chronic pain in underserved community clinics and for incorporation within shared medical visits. It will inform a future, fully powered, effectiveness-implementation trial of GetActive+ to help address the chronic pain epidemic among older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT05782231; https://clinicaltrials.gov/study/NCT05782231. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52117.

Differential gene expression provides leads to environmentally regulated soybean seed protein content.

Soybean is an important global source of plant-based protein. A persistent trend has been observed over the past two decades that soybeans grown in western Canada have lower seed protein content than soybeans grown in eastern Canada. In this study, 10 soybean genotypes ranging in average seed protein content were grown in an eastern location (control) and three western locations (experimental) in Canada. Seed protein and oil contents were measured for all lines in each location. RNA-sequencing and differential gene expression analysis were used to identify differentially expressed genes that may account for relatively low protein content in western-grown soybeans. Differentially expressed genes were enriched for ontologies and pathways that included amino acid biosynthesis, circadian rhythm, starch metabolism, and lipid biosynthesis. Gene ontology, pathway mapping, and quantitative trait locus (QTL) mapping collectively provide a close inspection of mechanisms influencing nitrogen assimilation and amino acid biosynthesis between soybeans grown in the East and West. It was found that western-grown soybeans had persistent upregulation of asparaginase (an asparagine hydrolase) and persistent downregulation of asparagine synthetase across 30 individual differential expression datasets. This specific difference in asparagine metabolism between growing environments is almost certainly related to the observed differences in seed protein content because of the positive correlation between seed protein content at maturity and free asparagine in the developing seed. These results provided pointed information on seed protein-related genes influenced by environment. This information is valuable for breeding programs and genetic engineering of geographically optimized soybeans.

Addressing the Chronic Pain-Early Cognitive Decline Comorbidity Among Older Adults: Protocol for the Active Brains Remote Efficacy Trial.

BACKGROUND: Chronic pain and early cognitive decline, which are costly to treat and highly prevalent among older adults, commonly co-occur, exacerbate one another over time, and can accelerate the development and progression of Alzheimer disease and related dementias. We developed the first mind-body activity program (Active Brains [AB]) tailored to the needs of older adults with chronic pain and early cognitive decline. Results from our previous study strongly supported the feasibility of conducting AB remotely and provided evidence for improvements in outcomes. OBJECTIVE: We are conducting a single-blinded, National Institutes of Health stage-2, randomized clinical trial to establish the efficacy of AB versus a time-matched and dose-matched education control (Health Enhancement Program [HEP]) in improving self-reported and objective outcomes of physical, cognitive, and emotional functions in 260 participants. The methodology described in this paper was informed by the lessons learned from the first year of the trial. METHODS: Participants are identified and recruited through multidisciplinary clinician-referred individuals (eg, pain psychologists and geriatricians), the Rally Research platform, social media, and community partnerships. Interested participants complete eligibility screening and electronic informed consent. Baseline assessments include self-report, performance-based measures (eg, 6-min walk test) and objective measures (eg, Repeatable Battery for the Assessment of Neuropsychological Status). Participants are mailed a wrist-worn ActiGraph device (ActiGraph LLC) to passively monitor objective function (eg, steps) during the week between the baseline assessment and the beginning of the programs, which they continue to wear throughout the programs. After baseline assessments, participants are randomized to either AB or HEP and complete 8 weekly, remote, group sessions with a Massachusetts General Hospital psychologist. The AB group receives a Fitbit (Fitbit Inc) to help reinforce increased activity. Assessments are repeated after the intervention and at the 6-month follow-up. Coprimary outcomes include multimodal physical function (self-report, performance based, and objective). Secondary outcomes are cognitive function (self-report and objective), emotional function, and pain. RESULTS: We began recruitment in July 2022 and recruited 37 participants across 4 cohorts. Of them, all (n=37, 100%) have completed the baseline assessment, 26 (70%) have completed the posttest assessment, and 9 (24%) are actively enrolled in the intervention (total dropout: n=2, 5%). In the three cohorts (26/37, 70%) that have completed the AB or HEP, 26 (100%) participants completed all 8 group sessions (including minimal makeups), and watch adherence (1937/2072, 93.48%, average across ActiGraph and Fitbit devices) has been excellent. The fourth cohort is ongoing (9/37, 24%), and we plan to complete enrollment by March 2026. CONCLUSIONS: We aim to establish the efficacy of the AB program over a time-matched and dose-matched control in a live video-based trial and test the mechanisms through theoretically driven mediators and moderators. Findings will inform the development of a future multisite effectiveness-implementation trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05373745; https://classic.clinicaltrials.gov/ct2/show/NCT05373745. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47319.

The impact of a virtual mind-body program on resilience factors among international English-speaking adults with neurofibromatoses: secondary analysis of a randomized clinical trial.

PURPOSE: To test the effects of the Relaxation Response Resiliency Program - Neurofibromatosis (3RP-NF), a mind-body resilience program for people with NF, on resilience factors from baseline to post-treatment and 6- and 12-month follow-up. METHODS: This is a secondary analysis of a fully powered randomized clinical trial (RCT) of 3RP-NF and health education control (HEP-NF). We recruited adults with NF1, NF2, or schwannomatosis who reported stress or difficulty coping with NF symptoms. Both conditions received 8 weekly 90-minute group sessions; 3RP-NF focused on building resilience skills. We measured resilience factors via the Measure of Current Status-A (adaptive coping), Cognitive and Affective Mindfulness Scale-Revised (mindfulness), Gratitude Questionnaire-6 (gratitude), Life Orientation Test Optimism Scale (optimism), and Medical Outcomes Study Social Support Survey (perceived social support) at baseline, post-intervention, and 6- and 12-month follow-up. We used linear mixed models with completely unstructured covariance across up to four repeated measurements (baseline, post-treatment, and 6- and 12-month follow-up) to investigate treatment effects on resilience factors. RESULTS: We enrolled 228 individuals (Mage=42.7, SD = 14.6; 74.5% female; 87.7% White; 72.8% NF1, 14.0% NF2, 13.2% schwannomatosis). Within groups, both 3RP-NF and HEP-NF showed statistically significant improvements in all outcomes across timepoints. 3RP-NF showed significantly greater improvement in adaptive coping compared to HEP-NF from baseline to post-intervention and baseline to 6 months (Mdifference= 0.29; 95% CI 0.13-0.46; p < 0.001; Mdifference= 0.25; 95% CI 0.07-0.33; p = 0.005); there were no other between-group differences amongst the remaining resilience factors. CONCLUSION: 3RP-NF showed promise in sustainably improving coping abilities amongst people with NF. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03406208. Registration submitted December 6, 2017, first patient enrolled October 2017.

Large-scale data mining pipeline for identifying novel soybean genes involved in resistance against the soybean cyst nematode.

The soybean cyst nematode (SCN) [Heterodera glycines Ichinohe] is a devastating pathogen of soybean [Glycine max (L.) Merr.] that is rapidly becoming a global economic issue. Two loci conferring SCN resistance have been identified in soybean, Rhg1 and Rhg4; however, they offer declining protection. Therefore, it is imperative that we identify additional mechanisms for SCN resistance. In this paper, we develop a bioinformatics pipeline to identify protein-protein interactions related to SCN resistance by data mining massive-scale datasets. The pipeline combines two leading sequence-based protein-protein interaction predictors, the Protein-protein Interaction Prediction Engine (PIPE), PIPE4, and Scoring PRotein INTeractions (SPRINT) to predict high-confidence interactomes. First, we predicted the top soy interacting protein partners of the Rhg1 and Rhg4 proteins. Both PIPE4 and SPRINT overlap in their predictions with 58 soybean interacting partners, 19 of which had GO terms related to defense. Beginning with the top predicted interactors of Rhg1 and Rhg4, we implement a "guilt by association" in silico proteome-wide approach to identify novel soybean genes that may be involved in SCN resistance. This pipeline identified 1,082 candidate genes whose local interactomes overlap significantly with the Rhg1 and Rhg4 interactomes. Using GO enrichment tools, we highlighted many important genes including five genes with GO terms related to response to the nematode (GO:0009624), namely, Glyma.18G029000, Glyma.11G228300, Glyma.08G120500, Glyma.17G152300, and Glyma.08G265700. This study is the first of its kind to predict interacting partners of known resistance proteins Rhg1 and Rhg4, forming an analysis pipeline that enables researchers to focus their search on high-confidence targets to identify novel SCN resistance genes in soybean.

Cannabinoid Therapy: Attitudes and Experiences of People With Chronic Pain.

OBJECTIVE: Clinical trials of cannabinoids for chronic pain have mixed and often inconclusive results. In contrast, many prospective observational studies show the analgesic effects of cannabinoids. This survey study aimed to examine the experiences/attitudes of individuals with chronic pain who are currently taking, have previously taken, or never taken cannabinoids for chronic pain to inform future research. METHODS: This study is based on a cross-sectional, web-based survey of individuals with self-reported chronic pain. Participants were invited to participate through an email that was distributed to the listservs of patient advocacy groups and foundations that engage individuals with chronic pain. RESULTS: Of the 969 respondents, 444 (46%) respondents reported currently taking, 213 (22%) previously taken, and 312 (32%) never taken cannabinoids for pain. Participants reported using cannabinoids to treat a wide variety of chronic pain conditions. Those currently taking cannabinoids (vs previously) more frequently reported: (1) large improvements from cannabinoids in all pain types, including particularly difficult-to-treat chronic overlapping pain conditions (eg, pelvic pain), (2) improvements in comorbid symptoms (eg, sleep), and (3) lower interference from side effects. Those currently taking cannabinoids reported more frequent and satisfactory communication with clinicians regarding cannabinoid use. Those never taken cannabinoids reported a lack of suggestion/approval of a clinician (40%), illegality (25%), and lack of FDA regulation (19%) as reasons for never trying cannabinoids. CONCLUSION: These findings underscore the importance of conducting high-quality clinical trials that include diverse pain populations and clinically relevant outcomes that if successful, could support FDA approval of cannabinoid products. Clinicians could then prescribe and monitor these treatments similarly to other chronic pain medications.

Initial Validation of the Intentions to Co-Use Alcohol and Opioids Scale.

Co-use of alcohol and prescription opioid medication increases risk for harmful and potentially fatal health effects (e.g., overdose). Behavioral intentions (i.e., the immediate antecedent of corresponding behavior according to the Theory of Planned Behavior) are important in prediction of substance use, and a valid measure assessing intentions to co-use alcohol and opioids is needed to identify individuals at-risk for harmful substance use. The goal of the current study was to develop and conduct the psychometric validation of a six-item Intentions to Co-Use Alcohol and Opioids (ICAO) scale. Participants included 261 (Mage = 38; 64% male) past-month drinkers with a current opioid prescription and chronic musculoskeletal pain who completed a targeted online survey. Confirmatory factor analysis indicated that a single-factor structure provided good model fit (Bollen-Stine bootstrap p = .121). Moreover, the ICAO demonstrated high internal consistency (α = .96) and was correlated with measures of alcohol and opioid use/co-use. These findings provide support for the single-factor structure, reliability, and concurrent/convergent validity of the ICAO among individuals who endorse alcohol use, opioid use, and chronic musculoskeletal pain. The ICAO may offer clinical utility as a tool to identify individuals at greater risk of potentially fatal co-use of alcohol and opioid medications.

Benzodiazepine Use and Dependence in Relation to Chronic Pain Intensity and Pain Catastrophizing.

Benzodiazepines (BZDs), a class of sedative-hypnotic medications, generated concern as their popularity grew, with particular alarm regarding elevated rates of BZD use among chronic pain populations. Consistent with negative reinforcement/motivational models of substance use, desire for pain alleviation may motivate BZD use. Yet, little is known about relations between pain and addiction-relevant BZD use processes. This cross-sectional survey study aimed to: a) test associations between pain intensity and clinically relevant BZD use patterns, and b) examine the role of pain catastrophizing in hypothesized pain-BZD relations. Participants included 306 adults with chronic musculoskeletal pain and a current BZD prescription who completed an online survey study (Mage = 38.7, 38.9% female). Results indicated that pain intensity was positively associated with past-month BZD use frequency, BZD dependence severity, and likelihood of endorsing BZD misuse behaviors (ps < .05). Pain catastrophizing was positively associated with BZD dependence/likelihood of BZD misuse, covarying for pain intensity (P < .05). These findings build upon an emerging literature by highlighting positive covariation of pain intensity and pain catastrophizing with addiction-relevant BZD use behaviors. Results underscore the need to further investigate high-risk BZD use among individuals with chronic pain, with and without concurrent opioid use, to inform prevention/intervention efforts. PERSPECTIVE: This article presents findings on cross-sectional associations of pain intensity and pain catastrophizing with clinically relevant benzodiazepine (BZD) use outcomes, including dependence and misuse, among individuals with chronic pain. Findings help elucidate the higher burden of BZD misuse/dependence in chronic pain populations and suggest that pain relief may be a common, yet under recognized, self-reported motivation for taking BZDs.

GmSWEET29 and Paralog GmSWEET34 Are Differentially Expressed between Soybeans Grown in Eastern and Western Canada.

Over the past two decades soybeans grown in western Canada have persistently had lower seed protein than those grown in eastern Canada. To understand the discrepancy in seed protein content between eastern- and western-grown soybeans, RNA-seq and differential expression analysis have been investigated. Ten soybean genotypes, ranging from low to high in seed protein content, were grown in four locations across eastern (Ottawa) and western (Morden, Brandon, and Saskatoon) Canada. Differential expression analysis revealed 34 differentially expressed genes encoding Glycine max Sugars Will Eventually be Exported Transporters (GmSWEETs), including paralogs GmSWEET29 and GmSWEET34 (AtSWEET2 homologs) that were consistently upregulated across all ten genotypes in each of the western locations over three years. GmSWEET29 and GmSWEET34 are likely candidates underlying the lower seed protein content of western soybeans. GmSWEET20 (AtSWEET12 homolog) was downregulated in the western locations and may also play a role in lower seed protein content. These findings are valuable for improving soybean agriculture in western growing regions, establishing more strategic and efficient agricultural practices.

Novel QTL for Low Seed Cadmium Accumulation in Soybean.

Soybean is a valuable crop, used in animal feed and for human consumption. Selecting soybean cultivars with low seed cadmium (Cd) concentration is important for the purpose of minimizing the transfer of Cd into the human body. To ensure international trade, farmers need to produce soybean that meets the European Union (EU) Cd limit of 0.2 mg kg-1. In this study, we evaluated two populations of recombinant inbred lines (RILs), X5154 and X4050, for seed Cd accumulation. Linkage maps were constructed with 325 and 280 polymorphic simple sequence repeat (SSR) markers, respectively, and used to identify a novel minor quantitative trait locus (QTL) on chromosome 13 in the X4050 population between SSR markers Satt522 and Satt218. Based on a gene ontology search within the QTL region, seven genes were identified as candidates responsible for low seed Cd accumulation, including Glyma.13G308700 and Glyma.13G309100. In addition, we confirmed the known major gene, Cda1, in the X5154 population and developed KASP and CAPS/dCAPS allele-specific markers for efficient marker-assisted breeding for Cda1.

Pain Intensity, Emotion Dysregulation, and Hazardous Drinking Among Adults With Chronic Pain.

OBJECTIVE: Chronic pain and hazardous alcohol use (i.e., a pattern of alcohol consumption that increases risk for harmful consequences) are prevalent and frequently comorbid conditions that have been posited to interact in a bidirectional manner, leading to greater pain and heavier drinking. Despite evidence that emotion dysregulation (i.e., difficulty modulating emotional responses when experiencing negative emotions) is independently associated with both greater pain and greater alcohol consumption, we are not aware of any previous research examining relations between emotion dysregulation, pain intensity, and hazardous alcohol use among individuals with chronic pain. METHOD: Participants included 125 past-month alcohol users with chronic musculoskeletal pain (38.4% female; mean age = 32.97 years; mean drinks/day = 1.62) who were recruited for an online survey study of pain and substance use. RESULTS: As expected, emotion dysregulation was positively associated with increased odds of hazardous alcohol use. We also observed a significant indirect association, such that higher levels of emotion dysregulation were associated with greater pain intensity, which in turn was associated with a greater likelihood of scoring above the Alcohol Use Disorders Identification Test cutoff for hazardous alcohol use. CONCLUSIONS: These findings suggest that emotion dysregulation may contribute to hazardous drinking among individuals with chronic pain, perhaps indirectly via pain amplification. Emotion dysregulation warrants consideration as a potential transdiagnostic vulnerability factor in comorbid chronic pain and hazardous drinking. Future prospective research is needed to examine causal pathways and establish temporal precedence.

Concerning the Etiology of Syrah Decline: A Fresh Perspective on an Old and Complex Issue Facing the Global Grape and Wine Industry.

Syrah decline, first identified in Southern France in the 1990s, has become a major concern in the global grape and wine industry. This disease mainly affects Syrah (Shiraz) grapevines. Characteristic symptoms include the bright and uniform reddening of leaves throughout the canopy in late summer or early fall; the appearance of abnormalities on the trunk, mainly at the graft union (swelling, pits, grooves, and necrosis); and a reduction in vine vigor, yield and berry quality. Diseased vines may die a few years after disease onset. Damages to the vine are even more pronounced in cool climate regions such as Ontario (Canada), where the affected vines are subjected to very cold and prolonged winters, leading to large numbers of vine deaths. Despite the extensive efforts of the global grape research community over the past few decades, the etiology of this disease remains unclear. In this study, we conducted extensive analyses of viruses in declining Syrah vines identified in commercial vineyards in the Niagara region (Ontario, Canada) through high-throughput sequencing, PCR, RT-PCR and the profiling of genetic variants of select viruses. Multiple viruses and viral strains, as well as three viroids, were identified. However, an unequivocal causal relationship cannot be established between Syrah decline and any of these viruses, although the possibility that certain virus or genetic variants, or both in combination, may contribute to the disease cannot be excluded. Gleaning all information that is available to date, we feel that the traditional approach and an insistence on finding a single cause for such a complex disorder in a woody perennial fruit crop involving grafting will prove to be futile. We hope that this study offers new conceptual perspectives on the etiology of this economically important but enigmatic disease complex that affects the global grape and wine industry.

A Multi-Year, Multi-Cultivar Approach to Differential Expression Analysis of High- and Low-Protein Soybean (Glycine max).

Soybean (Glycine max (L.) Merr.) is among the most valuable crops based on its nutritious seed protein and oil. Protein quality, evaluated as the ratio of glycinin (11S) to ß-conglycinin (7S), can play a role in food and feed quality. To help uncover the underlying differences between high and low protein soybean varieties, we performed differential expression analysis on high and low total protein soybean varieties and high and low 11S soybean varieties grown in four locations across Eastern and Western Canada over three years (2018-2020). Simultaneously, ten individual differential expression datasets for high vs. low total protein soybeans and ten individual differential expression datasets for high vs. low 11S soybeans were assessed, for a total of 20 datasets. The top 15 most upregulated and the 15 most downregulated genes were extracted from each differential expression dataset and cross-examination was conducted to create shortlists of the most consistently differentially expressed genes. Shortlisted genes were assessed for gene ontology to gain a global appreciation of the commonly differentially expressed genes. Genes with roles in the lipid metabolic pathway and carbohydrate metabolic pathway were differentially expressed in high total protein and high 11S soybeans in comparison to their low total protein and low 11S counterparts. Expression differences were consistent between East and West locations with the exception of one, Glyma.03G054100. These data are important for uncovering the genes and biological pathways responsible for the difference in seed protein between high and low total protein or 11S cultivars.

Human-Soybean Allergies: Elucidation of the Seed Proteome and Comprehensive Protein-Protein Interaction Prediction.

The soybean crop, Glycine max (L.) Merr., is consumed by humans, Homo sapiens, worldwide. While the respective bodies of literature and -omics data for each of these organisms are extensive, comparatively few studies investigate the molecular biological processes occurring between the two. We are interested in elucidating the network of protein-protein interactions (PPIs) involved in human-soybean allergies. To this end, we leverage state-of-the-art sequence-based PPI predictors amenable to predicting the enormous comprehensive interactome between human and soybean. A network-based analytical approach is proposed, leveraging similar interaction profiles to identify candidate allergens and proteins involved in the allergy response. Interestingly, the predicted interactome can be explored from two complementary perspectives: which soybean proteins are predicted to interact with specific human proteins and which human proteins are predicted to interact with specific soybean proteins. A total of eight proteins (six specific to the human proteome and two to the soy proteome) have been identified and supported by the literature to be involved in human health, specifically related to immunological and neurological pathways. This study, beyond generating the most comprehensive human-soybean interactome to date, elucidated a soybean seed interactome and identified several proteins putatively consequential to human health.

Feasibility of Computerized Cognitive-Behavioral Therapy Combined With Bifrontal Transcranial Direct Current Stimulation for Treatment of Major Depression.

BACKGROUND: Cognitive behavioral therapy (CBT) is effective in the treatment of major depressive disorder (MDD). Transcranial Direct Current Stimulation (tDCS) has demonstrated preliminary antidepressant effects and beneficial effects on cognitive function. OBJECTIVE: We investigated the feasibility and acceptability of using tDCS to enhance the effects of computer-based CBT for treatment of MDD. MATERIALS AND METHODS: In a randomized, double-blind, sham-controlled study, 14 patients with MDD on stable or no pharmacotherapy received active or sham bifrontal tDCS for four weeks with concurrent CBT. RESULTS: Ten participants completed the protocol. Three withdrew from the study because of lack of efficacy or dislike of the eCBT program. One was discontinued from the protocol by the investigators. Treatment was well tolerated, and most side-effects were mild and consistent with prior tDCS research. Pooled data from both groups showed significant baseline to endpoint improvement in depression (p = 0.008). Overall percent change on the HAMD-21 was 28.98%. The study was underpowered to detect differences in tDCS treatment groups. CONCLUSIONS: Combining tDCS with computer-based CBT is feasible for MDD. Further work is needed to evaluate potential synergistic effects of combined tDCS and CBT.