Disease Symptoms Research Articles

Mapping of a novel locus Ra conferring extreme resistance against potato virus A in cultivated potato (Solanum tuberosum L.).

The Ra extreme resistance against potato virus A was mapped to the upper of chromosome 4 in tetraploid potato. Potato virus A (PVA) is one of the major viruses affecting potato worldwide and can cause serious disease symptoms and yield losses. Previously, we determined that potato cultivar Barbara harbors Rysto (genotype: Ryryryry) and Ra (genotype: Rararara) that each independently confer extreme resistance to PVA. In this study, employing a combination of next-generation sequencing and bulked-segregant analysis, we further located this novel Ra on chromosome 4 using a tetraploid BC1 potato population derived from a Ry-free progeny (Rararararyryryry) of Barbara (RarararaRyryryry) × F58050 (rararararyryryry). Using 29 insertion-deletion (InDel) markers spanning chromosome 4, Ra was delimited by the InDel markers M8-83 and M10-8 within a genetic interval of 1.46cM, corresponding to a 1.86-Mb genomic region in the potato DM reference genome. The InDel marker M10-8, which is closely linked with the resistance against PVA in the Ry-free segregating populations, was then used to screen 43 selected Rysto-free tetraploid potato breeding clones. The phenotype to PVA was significantly correlated with the present/absent of the marker, albeit with a 9.3% false positive rate and a 14.0% false negative rate. These findings are of importance in furthering the cloning of Ra and employing the marker-assisted selection for PVA resistance.

Dietary habits in Italian children with inflammatory bowel disease: A case-control multicenter study.

Patients with inflammatory bowel disease (IBD) tend to self-modify their dietary habits according to disease activity and symptoms. This study aimed to assess the adequacy of the usual diet in Italian children with IBD in comparison to a control group and to the recommended dietary allowances (RDA). Dietary habits of IBD children and age- and gender-matched healthy controls were investigated using a validated Food Frequency Questionnaire in five Italian pediatric IBD centers. Adherence to the Mediterranean diet (MD) was assessed using the KID-MED test. Energy (EI), macro, and micronutrients intakes were compared between the two groups, to the RDA and the predicted total energy expenditure (EI/total energy expenditure [TEE]%). IBD subjects (n = 110) reported a lower EI, EI/RDA%, and EI/TEE% compared to controls (n = 110) (p = 0.012, p < 0.0002, and p = 0.014), lower total protein and fat intakes (p = 0.017, p < 0.0001) and lower minerals/RDA, vitamins/RDA and micronutrients/RDA ratio (%). Poor adherence to the MD was more frequent in IBD children compared to controls (p = 0.013). The total EI and carbohydrate intake were inversely correlated with higher disease activity. Italian children with IBD report an inadequate diet in terms of energy, macro, and micronutrients and have a low adherence to a high-quality MD pattern.

IL-10+ regulatory B cells mitigate atopic dermatitis by suppressing eosinophil activation

Atopic dermatitis (AD) presents significant therapeutic challenges due to its poorly understood etiology. Eosinophilia, a hallmark of allergic inflammation, is implicated in AD pathogenesis. Interleukin-10 (IL-10)-producing regulatory B (Breg) cells exhibit potent anti-inflammatory effects. However, their role in controlling AD-related eosinophilia is not well understood. To investigate the impact of eosinophils on AD, we employed IL-5Rα-deficient (Il5ra−/−) mice, which lack functional eosinophils. Induction of AD in these mice resulted in attenuated disease symptoms, underscoring the critical role of eosinophils in AD development. Additionally, the adoptive transfer of purified Breg cells into mice with AD significantly alleviated disease severity. Mechanistic studies revealed that IL-10 produced by Breg cells directly inhibits eosinophil activation and infiltration into the skin. In vitro experiments further confirmed that Breg cells inhibited eosinophil peroxidase secretion in an IL-10-dependent manner. Our collective findings demonstrate that IL-10 from Breg cells alleviates AD by suppressing eosinophil activation and tissue infiltration. This study elucidates a novel regulatory mechanism of Breg cells, providing a foundation for future Breg-mediated therapeutic strategies for AD.

Rapid Detection of Viral, Bacterial, Fungal, and Oomycete Pathogens on Tomatoes with Microneedles, LAMP on a Microfluidic Chip, and Smartphone Device.

Rapid detection of plant diseases before they escalate can improve disease control. Our team has developed rapid nucleic acid extraction methods with microneedles and combined these with loop-mediated amplification (LAMP) assays for pathogen detection in the field. In this work, we developed LAMP assays for early blight (Alternaria linariae, A. alternata, and A. solani) and bacterial spot of tomato (Xanthomonas perforans) and validated these LAMP assays and two previously developed LAMP assays for tomato spotted wilt virus and late blight. Tomato plants were inoculated, and disease severity was measured. Extractions were performed using microneedles, and LAMP assays were run in tubes (with hydroxynaphthol blue) on a heat block or on a newly designed microfluidic slide chip on a heat block or a slide heater. Fluorescence on the microfluidic chip slides was visualized using EvaGreen and photographed on a smartphone. Plants inoculated with X. perforans or tomato spotted wilt virus tested positive prior to visible disease symptoms, whereas Phytophthora infestans and A. linariae were detected at the time of visual disease symptoms. LAMP assays were more sensitive than PCR, and the limit of detection was 1 pg of DNA for both A. linariae and X. perforans. The LAMP assay designed for early blight detected all three species of Alternaria that infect tomato and is thus an Alternaria spp. assay. This study demonstrates the utility of rapid microneedle extraction followed by LAMP on a microfluidic chip for rapid diagnosis of four important tomato pathogens.

Tear α-synuclein as a biomarker for Parkinson's disease: A systematic review and meta-analysis.

Parkinson's disease symptoms mostly manifest after significant and irreversible neuropathology. Hence, there is a need to identify biomarkers that can provide indications of disease before significant neuronal degeneration occurs. To estimate the difference in the concentration of α-synuclein protein in tears between individuals with Parkinson's disease and healthy controls. PubMed, Scopus, and Web of Science. The last database search was on December 20, 2023. Primary prospective studies in humans measuring the level of α-synuclein in tears and clinical outcomes reported using mean or median. Individuals with Parkinson's disease and healthy controls. The risk of bias was assessed using the Newcastle-Ottawa Scale. The I2 statistic was used to estimate heterogeneity. The outcome measure was the difference in tear total and oligomeric α-synuclein. Mean difference (MD) was used to assess the outcome. The certainty of evidence was rated following the Grading of Recommendations Assessment and Development and Evaluation (GRADE) system. Three hundred twenty-seven Parkinson's disease and 312 healthy control subjects from five studies and 177 Parkinson's disease and 166 healthy control subjects from two studies were included in total α-synuclein levels and oligomeric α-synuclein levels analysis, respectively. Total α-synuclein level was not different between Parkinson's disease and healthy controls (MD = 0.02 ng/mL [95% confidence interval {CI}: 0.00 to 0.05 ng/mL; I2 = 90%; Z = 1.79; p=0.07; number of studies = 5; GRADE rating = very low]). Stratifying the data based on disease duration, total α-synuclein was higher in subjects with Parkinson's disease duration ≥7 years compared with healthy controls (MD = 0.04 ng/mL [95% CI: 0.03 to 0.05 ng/mL; I2 = 0%; Z = 8.24, p<0.00001; number of studies = 2; GRADE rating = low]) but not different between the two groups (MD = -0.12 ng/mL (95% CI: -0.38 to 0.15 ng/mL; I2 = 93%; Z = 0.84, p=0.40; number of studies = 3; GRADE rating = very low]). Oligomeric α-synuclein level was higher in Parkinson's disease compared with controls (MD = 6.50 ng/mL [95% CI: 2.79 to 10.20 ng/mL; I2 = 94%; Z = 3.44; p=0.0006; number of studies = 2; GRADE rating = very low]). High heterogeneity between studies. Potential sources of heterogeneity could not be explored due to the limited number of studies. Tear α-synuclein has the potential to be a noninvasive biomarker for Parkinson's disease. Studies are, however, needed to increase certainty in the biomarker and establish how the protein's changes in tears correlate with Parkinson's disease progression and severity.

Management of late blight (Phytophthora infestans) of potato (Solanum tuberosum) through efficient spray schedule of fungicides in the north-eastern Himalayan region of India

Phytophthora infestans (Mont.) de Bary, belongs to order Peronosporales is one of the most destructive phytopathogen causing late blight disease of potato (Solanum tuberosum L.). The disease symptoms appear on leaf, petiole, stem, and tubers at any stage of crop growth and may cause severe disease epidemics leading to complete defoliation and extensive yield loss. The field experiments were conducted during 2020–21 and 2021–22 at Chesrimai GP, Charilam block, Sepahijala, Tripura to find out the effective management strategies with fungicides to mitigate the losses caused by the devastating disease. The experiment was laid out in a randomized block design (RBD) in 3 replications with 8 treatments having different fungicides in different combinations for determining the best spray schedule against late bight disease. Results revealed that one spraying of Mancozeb 75% @0.25% at 35 days after sowing (DAS), second spraying of Cymoxanil 8% + Mancozeb 64% @0.25% at 42 DAS, and third spraying of Mancozeb 75% @0.25% at 49 DAS and fourth spraying of Cymoxanil 8% + Mancozeb 64% @ 0.25% at 56 DAS recorded the best performing treatment, with the least mean disease severity (10.54 and 7.30%), the least mean disease incidence (15.00 and 12.75%), the least coefficient of disease index (CODEX) value (1.58% and 0.93%), and highest tuber yield (21.27 and 21.68 t/ha) during 2020–21 and 2021–22, respectively. In addition, there were 26.6 and 27.7% increase in yield over control during 2020–21 and 2021–22, respectively and the pooled incremental cost benefit ratio (ICBR) of 1:16.09 was found to be highest among all other treatments. Efficient spray schedule of prophylactic/ preventive spray with contact fungicide followed by spraying with translaminar/systemic + contact fungicide can effectively manage the late blight disease of potato under field conditions.

Localization of Iris Yellow Spot Virus in Naturally Infected Onion Plants: A Sampling Approach for Reliable Diagnosis

Iris yellow spot virus (IYSV) from the genus Orthotospovirus of the family Tospoviridae can cause considerable yield reduction and crop loss in allium crops, especially dry bulb onion. While infected plants may or may not express symptoms of iris yellow spot disease, these onion plants can test negative for the virus because not all tissues contain detectable levels of IYSV due to its uneven distribution. The purpose of this study was to identify tissue locations of symptomatic onion plants that have the highest likelihood of testing positive for IYSV in DAS-ELISA using specific antibodies. Results revealed that the greatest likelihood of detecting IYSV from a single symptomatic plant occurred with tissue near foliar lesions located on the distal portions of older leaves (range: 42-71%). These low to moderate probability detection levels can predictably be overcome by testing pooled tissue samples from the same plant or from multiple plants. Indeed, the likelihood of distal and proximal youngest leaf tissue testing positive for IYSV from a single plant to a four-plant composite sample would increase from 44% to 90% and from 50% to 94%, respectively. Implications of these results for IYSV detection and surveillance in onion production systems are discussed.

Insomnia in Parkinson's Disease: Causes, Consequences, and Therapeutic Approaches.

Sleep disorders represent prevalent non-motor symptoms in Parkinson's disease (PD), affecting over 90% of the PD population. Insomnia, characterized by difficulties in initiating and maintaining sleep, emerges as the most frequently reported sleep disorder in PD, with prevalence rates reported from 27 to 80% across studies. Insomnia not only significantly impacts the quality of life of PD patients but is also associated with cognitive impairment, motor disabilities, and emotional deterioration. This comprehensive review aims to delve into the mechanisms underlying insomnia in PD, including neurodegenerative changes, basal ganglia beta oscillations, and circadian rhythms, to gain insights into the neural pathways involved. Additionally, the review explores the risk factors and comorbidities associated with insomnia in PD, providing valuable insights into its management. Special attention is given to the challenges faced by healthcare providers in delivering care to PD patients and the impact of caregiving roles on patients' quality of life. Overall, this review provides a comprehensive understanding of insomnia in PD and highlights the importance of addressing this common sleep disorder in PD patients.

Blood Biomarkers of Long COVID: A Systematic Review.

Long coronavirus disease (COVID; LC) affects millions of people worldwide. The exact mechanisms which result in a broad, undulating and detrimental symptom profile remain unknown. Blood biomarkers associated with LC have been described; however, consensus on these remains elusive, in part due to a lack of continuity between studies on a universally accepted definition of LC. This systematic review aimed to consolidate current knowledge of blood biomarkers associated with the prevalence of LC on the basis of the World Health Organisation (WHO) clinical definition of this condition. Observational, cross-sectional, and randomised control studies published in the English language that studied blood biomarkers associated with the WHO definition of LC. All studies included participants who were ≥ 18 years old and group sizes ≥ 10 participants, and were compared against a control group without any known co-morbidities. A systematic literature search was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered on Prospero (ID: CRD42022373121). The Cochrane, Embase, PubMed and Web of Science databases were searched from inception to January 2024. Search results were gathered using Rayyan software and data extracted using Microsoft Excel. The reporting recommendations for tumour markers prognostic studies (REMARK) questionnaire was used to assess the quality of the included studies. A total of 45 observational and one interventional study comprising 4415 participants were included in this review which identified 525 blood biomarkers thought to be associated with LC. Three blood biomarker subtypes were associated with the development of LC: (1) immunological and inflammatory dysfunction, (2) endothelial/vascular dysfunction and (3) metabolic and clotting abnormalities. Our data are consistent with previous findings; however, no single biomarker was sufficiently associated with LC prevalence and instead a profile of biomarkers across various physiological systems may be more clinically useful. In all, 196 studies were excluded due to a lack of an adequately healthy comparator group and/or failure to meet the WHO LC definition. This demonstrates a need for further research incorporating a universal LC definition across all disease severity groups and symptom profiles, and longitudinal data reflecting the relapsing and remitting nature of this condition. Further investigation into blood biomarkers of LC, including clear reporting of healthy comparator groups and the investigation of acute and chronic biomarker changes, within the context of medical practice, may support the development of curative/restorative approaches.

ASSESSMENT FOR RESISTANCE GENES AGAINST PATHOGEN VENTURIA PYRINA ADERH. IN LOCAL, SELECTED AND INTRODUCED VARIETIES OF PEAR CULTIVATED IN AZERBAIJAN

Pear scab (Venturia pyrina Aderh.) is the most perilous fungal disease of the pear plant and from an economic point of view, it causes considerable crop loss in the orchards of our country. Fungicides are mainly used to treat trees to struggle disease. The use of resistant cultivars in production of disease control is most important alternative ways. For this purpose, in our experiment, we found out whether local, selected and introduced pear varieties of Azerbaijan are durable to the pathogen Venturia pyrina Aderh. The seedlings taken for this purpose are thoroughly infected by spraying on 3-5 leaves. The durable of selected pear cultivars to the pathogen Venturia pyrina was basically defined by Chevalier et al. was estimated with a 4-point system and the research results were analysed accordingly. 12% of the plants were scored 1 for the absence of disease symptoms, 29% were scored 2 and 3a for poorly formed spores, but 59% were scored 3b and 4 due to the presence of junior lesions. Among local pear cultivars, Gorkhmazi, Nar, Gov, Ispiya, Cir, Khirda serchebudu, Sini, Uzunbogaz, Boyuk uzunbogaz, selected pear varieties Form3, Form7, introduced pear varieties William, Clapp's favorite and Cure were found to be more infected. Highly durable pear various identified during the study can be used for pear scab introgression in breeding programs.

Clinical and economic assessment of using topical bacterial lysate Imudon® for the treatment and prevention of acute upper respiratory tract infections in children

Objective: pharmacoeconomic analysis of the feasibility of using topical bacterial lysate Imudon® for the treatment and prevention of acute upper respiratory tract infections in the pediatric population in comparison with other medicines belonging to the class of topical antiseptics.Material and methods. For the population calculated on the basis of Rosstat data, taking into account the Russian clinical recommendations "Acute respiratory viral infection (ARVI)" and "Acute tonsillitis and pharyngitis (acute tonsillopharyngitis)", the direct medical costs of medical care were determined. The cost of basic therapy of 1 case of acute respiratory infection (ARI) with symptoms of pharyngitis was calculated for two variants of clinical course: favorable (when ARI proceeds without complications and the patient does not need to be prescribed antibacterial drugs), and unfavorable (when confirmed bacterial infection joins and antibiotics are required). The indirect costs of child care are associated with lost gross domestic product (GDP). In estimating the GDP shortfall, it was assumed that the parent does not contribute to the country’s GDP during the entire childcare period.Results. GDP per capita for 2022 amounted to 2853.13 rubles per day. Thus, with a favorable course of the disease, indirect costs will be 19,972 rubles, and with an unfavorable course – 39,944 rubles. The total costs of the healthcare system and the state for 1 ARI patient are 32,192 rubles in case of favorable course and 71,644 rubles in case of unfavorable course. Imudon® administration allows reducing direct costs of parents for purchase of medicines for treatment of 1 ARI case by 23.6% compared to the therapeutic strategy associated with the use of local antiseptics.Conclusion. For the first time in Russian economic conditions, the use of Imudon® for the treatment and prevention of acute upper respiratory tract infections in children was evaluated. Its use from the first ARI symptoms allows refusing the use of local antiseptics, shortens the duration of the disease symptoms, and reduces the need for antibiotics, i.e. is feasibleable compared to local antiseptics.

Identifying diseases symptoms and general rules using supervised and unsupervised machine learning

The symptoms of diseases can vary among individuals and may remain undetected in the early stages. Detecting these symptoms is crucial in the initial stage to effectively manage and treat cases of varying severity. Machine learning has made major advances in recent years, proving its effectiveness in various healthcare applications. This study aims to identify patterns of symptoms and general rules regarding symptoms among patients using supervised and unsupervised machine learning. The integration of a rule-based machine learning technique and classification methods is utilized to extend a prediction model. This study analyzes patient data that was available online through the Kaggle repository. After preprocessing the data and exploring descriptive statistics, the Apriori algorithm was applied to identify frequent symptoms and patterns in the discovered rules. Additionally, the study applied several machine learning models for predicting diseases, including stepwise regression, support vector machine, bootstrap forest, boosted trees, and neural-boosted methods. Several predictive machine learning models were applied to the dataset to predict diseases. It was discovered that the stepwise method for fitting outperformed all competitors in this study, as determined through cross-validation conducted for each model based on established criteria. Moreover, numerous significant decision rules were extracted in the study, which can streamline clinical applications without the need for additional expertise. These rules enable the prediction of relationships between symptoms and diseases, as well as between different diseases. Therefore, the results obtained in this study have the potential to improve the performance of prediction models. We can discover diseases symptoms and general rules using supervised and unsupervised machine learning for the dataset. Overall, the proposed algorithm can support not only healthcare professionals but also patients who face cost and time constraints in diagnosing and treating these diseases.

Control of Mal secco disease in lemon by drip irrigation with fungicide

Mal secco disease of citrus is caused by the mitosporic ascomycete fungus Plenodomus tracheiphilus (formerly Phoma tracheiphila [Petri]). Mal secco is a highly destructive vascular disease of lemon and other citrus which is presently confined to the Mediterranean basin and has a marked economic impact on the citrus industry. The fungal pathogen infects the host tree by penetrating through wounds in the roots or canopy. Infection spreads quickly into the main branches and trunk and tree mortality usually ensues. The most typical symptoms are veinal chlorosis, leaf wilt, red discoloration of the xylem and dieback of twigs and branches. Current accepted control of the disease is mainly by sanitation of infected wood, and copper application during the winter to prevent germinating spores from infecting the plant. No effective chemical control for this disease has been reported. We present a drip-irrigation protocol to protect trees and control the disease in which we apply 250 g/ha of the triazole fungicide flutriafol five times a year. Progression of disease symptoms in the treated trees was inhibited by up to 81% compared to the untreated control, thereby significantly shortening the sanitation process and making it less costly than in untreated trees. Moreover, disease symptoms became less severe as the duration of treatment increased. We have treated orchards for 3 years, and present an effective commercial protocol for the growers which will help them control Mal secco disease.

Distinct Clinical Implications of Patient- Versus Clinician-Rated Motor Symptoms in Parkinson's Disease.

Patient-rated motor symptoms (PRMS) and clinician-rated motor symptoms (CRMS) often differ in Parkinson's disease (PD). Our goal was to investigate the determinants and clinical implications of PRMS compared with CRMS in PD. This retrospective, observational cohort study analyzed the cross-sectional associations and longitudinal impacts of PRMS as assessed by the Movement Disorders Society-sponsored Unified PD Rating Scale (MDS-UPDRS) part 2, while controlling for CRMS measured by MDS-UPDRS part 3. Longitudinal analyses used Cox proportional hazards models and multiple linear mixed-effects random intercepts/slope models, adjusting for many clinical predictors. We conducted propensity score matching (PSM) to reinforce our analyses' robustness and surface-based morphometry to investigate neural correlates. We enrolled 442 patients with early-stage PD. At baseline, regardless of CRMS, PRMS were associated with the severity of postural instability and gait disturbance (PIGD). Notably, PRMS independently and more accurately predicted faster long-term deterioration in motor function than CRMS (Hoehn and Yahr 4, adjusted hazard ratio per +1 point = 1.19 [95% confidence intervals, 1.08-1.32]), particularly in PIGD (PIGD subscore, β-interaction = 0.052 [95% confidence intervals, 0.018-0.086]). PSM confirmed these findings' robustness. Surface-based morphometry suggested that enhanced sensory processing was distinctively associated with PRMS. In early-stage PD, PRMS weighed different aspects of symptoms and more effectively predicted motor deterioration compared to CRMS, with distinctive brain structural characteristics. The superior sensitivity of PRMS to subtle declines in drug-refractory symptoms like PIGD likely underlie our results, highlighting the importance of understanding the differential clinical implications of PRMS to prevent long-term motor deterioration. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Earlier vs. later time period of COVID-19 infection and emergent autoimmune signs, symptoms, and serologies

ObjectiveAutoantibodies and autoimmune diseases after SARS-CoV-2 infection are widely reported. Given evolving variants, milder infections, and increasing population vaccination, we hypothesized that SARS-CoV-2 infection earlier in the pandemic would be associated with more autoimmune connective tissue disease (CTD) symptoms and immunologic abnormalities. MethodsPatients ≥18 years old with COVID-19 3/1/2020-8/15/2022 completed the CTD Screening Questionnaire and were tested for 27 autoimmune serologies, SARS-CoV-2 serologies, cell-bound complement activation products (CB-CAPs), and T and B lymphocyte immunophenotypes by flow cytometry. We assessed relationships between symptoms, serologies, and immunophenotypes in earlier (3/1/2020-1/31/2021) vs. later (2/1/2021-8/15/2022) periods, with different predominating SARS-CoV-2 viruses. Results57 subjects had earlier and 23 had later pandemic COVID-19. 35 % of earlier vs. 17 % of later pandemic patients had CTD symptoms (p 0.18). More patients were antinuclear antibody (ANA) positive (44 % vs. 13 %, p 0.01) and had lupus anticoagulant (11 % vs. 4 %, p 0.67). After adjustment for age, race, and sex, earlier (vs. later) COVID-19 was associated with increased ANA positivity (OR 4.60, 95%CI 1.17, 18.15). No subjects had positive CB-CAPs. T and B cell immunophenotypes and SARS-CoV-2 serologies did not differ by group. In heatmap analyses, higher autoantibody variety was seen among those with infection in the early pandemic. ConclusionIn this sample, having COVID-19 infection in the earlier (pre-2/1/2021) vs. later pandemic was associated with more CTD symptoms, ANA positivity, and autoantibody reactivities. Earlier SARS-CoV-2 variants circulating in a less vaccinated population with less natural immunity may have been more immunogenic.

Interactive regulation of immune-related resistance genes with salicylic acid and jasmonic acid signaling in systemic acquired resistance in the Xanthomonas–Brassica pathosystem

Pathogen-responsive immune-related genes (resistance genes [R-genes]) and hormones are crucial mediators of systemic acquired resistance (SAR). However, their integrated functions in regulating SAR signaling components in local and distal leaves remain largely unknown. To characterize SAR in the Xanthomonas campestris pv. campestris (Xcc)–Brassica napus pathosystem, the responses of R-genes, (leaf and phloem) hormone levels, H2O2 levels, and Ca2+ signaling-related genes were assessed in local and distal leaves of plants exposed to four Xcc-treatments: Non-inoculation (control), only secondary Xcc-inoculation in distal leaves (C-Xcc), only primary Xcc-inoculation in local leaves (Xcc), and both primary and secondary Xcc-inoculation (X-Xcc). The primary Xcc-inoculation provoked disease symptoms as evidenced by enlarged destructive necrosis in the local leaves of Xcc and X-Xcc plants 7 days post-inoculation. Comparing visual symptoms in distal leaves 5 days post-secondary inoculation, yellowish necrotic lesions were clearly observed in non Xcc-primed plants (C-Xcc), whereas no visual symptom was developed in Xcc-primed plants (X-Xcc), demonstrating SAR. Pathogen resistance in X-Xcc plants was characterized by distinct upregulations in expression of the PAMP-triggered immunity (PTI)-related kinase-encoding gene, BIK1, the (CC-NB-LRR-type) R-gene, ZAR1, and its signaling-related gene, NDR1, with a concurrent enhancement of the kinase-encoding gene, MAPK6, and a depression of the (TIR-NB-LRR-type) R-gene, TAO1, and its signaling-related gene, SGT1, in distal leaves. Further, in X-Xcc plants, higher salicylic acid (SA) and jasmonic acid (JA) levels, both in phloem and distal leaves, were accompanied by enhanced expressions of the SA-signaling gene, NPR3, the JA-signaling genes, LOX2 and PDF1.2, and the Ca2+-signaling genes, CAS and CBP60g. However, in distal leaves of C-Xcc plants, an increase in SA level resulted in an antagonistic depression of JA, which enhanced only SA-dependent signaling, EDS1 and NPR1. These results demonstrate that primary Xcc-inoculation in local leaves induces resistance to subsequent pathogen attack by upregulating BIK1-ZAR1-mediated synergistic interactions with SA and JA signaling as a crucial component of SAR.

The effect of astaxanthin supplementation on inflammatory markers, oxidative stress indices, lipid profile, uric acid level, blood pressure, endothelial function, quality of life, and disease symptoms in heart failure subjects

BackgroundHeart failure is a chronic and progressive disease where the heart muscle is unable to pump enough blood and oxygen to meet the body’s needs. Oxidative stress and inflammation are key elements in the development and progression of heart failure. Astaxanthin, a carotenoid, has strong anti-inflammatory and antioxidant effects that may protect the cardiovascular system. A study will evaluate the effect of astaxanthin supplementation on inflammatory status, oxidative stress, lipid profile, uric acid levels, endothelial function, quality of life, and disease symptoms in people with heart failure.MethodsThe current study is a double-blind controlled randomized clinical trial for 8 weeks, in which people with heart failure were randomly assigned to two groups: intervention (one capsule containing 20 mg of astaxanthin per day, n = 40) and placebo (one capsule containing 20 mg of maltodextrin per day, n = 40) will be divided. At the beginning and end of the intervention, uric acid, lipid profile, oxidative stress indices, inflammatory markers, blood pressure, nitric oxide, and anthropometric factors will be measured, and questionnaires measuring quality of life, fatigue intensity, shortness of breath, and appetite will be completed. SPSS version 22 software will be used for statistical analysis.DiscussionThere is a growing global interest in natural and functional food products. This RCT contributes to the expanding body of research on the potential benefits of astaxanthin in heart failure patients, including its antioxidant, lipid-lowering, and anti-inflammatory effects.Trial registrationIranian Registry of Clinical Trials IRCT20200429047235N3. Registered on 26 March 2024.

Chemotherapy-Induced Peripheral Neuropathy Impacts Quality of Life and Activities of Daily Living of Brazilian Multiple Myeloma Patients.

Survival in multiple myeloma (MM) has improved in the past years with the introduction of immunomodulators and proteasome inhibitors. However, chemotherapyinduced peripheral neuropathy (CIPN) is associated with both drug classes affecting Health- Related Quality of Life (HRQoL) and activities of daily living (ADL). We evaluated CIPN in MM patients to identify associated factors and impacts on HRQoL and ADL. This is a cross-sectional study with Brazilian patients from public and private health services. Patients were interviewed using validated tools to measure CIPN and HRQoL, along with sociodemographic and clinical questions. Logistic regression was used to assess the association of CIPN with sociodemographic, clinical, and HRQoL variables. In total, 217 patients were eligible for the study. The median age was 67, 50.9% were women, 51.6% had low income, 47.5% had low education, and 55.3% attended private health services. The chemotherapy regimen most used was the combination of cyclophosphamide, thalidomide, and dexamethasone (17.5%) among the 24 types of regimens found. Most patients (90.3%) had at least one CIPN symptom: 62.7% were severe, and 51.62% were extremely bothered ADL. Numbness was the most common symptom (40.6%). CIPN was independently associated with education, hospitalization, chemotherapy, side effects, disease symptoms, and global health status in HRQoL. MM patients showed a high frequency of CIPN, which affected ADL and impaired HRQoL. Early and accurate detection of CIPN and dose management in patients with thalidomide and bortezomib-based regimens should be performed to provide better treatment outcomes and avoid permanent disabilities.

The Dermatomyositis Disease Symptom Questionnaire (DM-DSQ): A Measure to Assess the Patient Experience of Dermatomyositis Symptoms.

Dermatomyositis (DM) symptoms negatively impact the quality of life of individuals living with the disease. Disease-specific, patient-reported outcome (PRO) instruments are needed to assess symptoms important to individuals with DM. This study conceptualized patient DM experience and disease activity definition, which refined development of a novel PRO instrument capturing patient-reported symptoms, the Dermatomyositis Disease Symptom Questionnaire (DM-DSQ). An observational, qualitative study was conducted with 30 individuals with DM (age ≥18 years) in the US. A 1-hour semi-structured interview, including concept elicitation and cognitive debriefing, was conducted with each participant. Inductive coding was used to identify concepts; a saturation analysis was conducted to confirm sample size. Concepts from transcripts were used to refine the preliminary conceptual model and DM-DSQ items. Concept elicitation analysis findings included disease symptoms (e.g., muscle weakness) and functional impacts (e.g., walking). The analysis achieved conceptual saturation: the first 5 interviews uncovered most of the concepts. During cognitive debriefing of the DMDSQ, participants found the items relevant, comprehensive, and easily understood (except for "skin sensitivity in sunlight"). The revised DM-DSQ content preliminarily appears valid in the patient population surveyed, pending further additions and debriefing based on refinement of the preliminary conceptual disease model and items. The DM-DSQ is being used in a phase 2 clinical trial and could become a valuable tool for studies evaluating PROs in patients with DM. Preliminary results indicate its content validity; extensive psychometric analysis using clinical trial data will determine its ability to capture symptoms for patients with DM.

GWAS Identifies DPP6 as Risk Gene of Cognitive Decline in Parkinson's Disease.

Cognitive decline is among the most common non-motor symptoms in Parkinson's disease (PD), while its physiological mechanisms remain poorly understood. Genetic factors constituted a fundamental determinant in the heterogeneity of cognitive decline among PD patients. However, the underlying genetic background was still less studied. To explore the genetic determinants contributing to cognitive decline in PD, we performed genome-wide survival analysis using a Cox proportional hazards model in a longitudinal cohort of 450 Chinese patients with PD, and further explored the functional effect of the target variant. Additionally, we built a clinical-genetic model by incorporating clinical characteristics and polygenic risk score (PRS) to predict cognitive decline in PD. The cohort was followed up for an average of 5.25 (SE = 2.46) years, with 95 incidents of cognitive impairment. We identified significant association between locus rs75819919 (DPP6) and accelerated cognitive decline (p = 8.63E-09, beta = 1.74, SE = 0.30). Dual-luciferase reporter assay suggested this locus might be involved in the regulation of DPP6 expression. Using data set from the UK Biobank, we identified rs75819919 was associated with cognitive performance in the general population. Incorporation of PRS increased the model's predictability, achieving an average AUC of 75.6% through fivefold cross-validation in 1000 iterations. These findings improve the current understanding of the genetic etiology of cognitive impairment in PD, and provide a novel target DPP6 to explore therapeutic options. Our results also demonstrate the potential to develop clinical-genetic model to identify patients susceptible to cognitive impairment and thus provide personalized clinical guidance.