Higher Disease Scores Research Articles

Optimizing pyrethrum planting dates to enhance productivity in a changing climate: A case of southern Highlands in Tanzania

Pyrethrum has excellent potential for growing and industrial production in Tanzania, offering an environmentally friendly alternative to synthetic pesticides and reducing pest and disease incidence without altering the natural balance. Planting date and seeding rate are critical for the productivity of pyrethrum; however, farmers in recent years have been experiencing climate change, resulting in unreliable planting periods. This study seeks to optimize the planting date for increased crop production. The study was conducted in the Umalila Highlands in the Mbeya region, with demonstration plots established in three villages (Iyunga Mapinduzi, Santilya, and Pashungu) and planted at monthly intervals from January to April. A randomized complete block design with three replications was used. The highest flower yield was achieved with early planting dates, particularly in January, with yields progressively decreasing from February to April. Sowing in January produced a yield of approx. 550 kg ha-1, significantly more than the April control with approx. 122 kg ha-1. The survival rate of Pyrethrum plants was highest at about 75% when planted in January and decreased to 72% in February, 67% in March and 57% in April. Pyrethrum planted in January had the most significant plant height, rosette size, and number of stems at all three sites, while April plantings had the worst performance and higher disease scores. Positive correlations were observed between yield and plant traits, such as height, rosette size, and number of stems, with negative correlations between yield and disease scores.

Proteomic insights into the pathophysiology of hypertension-associated albuminuria: Pilot study in a South African cohort

BackgroundHypertension is an important public health priority with a high prevalence in Africa. It is also an independent risk factor for kidney outcomes. We aimed to identify potential proteins and pathways involved in hypertension-associated albuminuria by assessing urinary proteomic profiles in black South African participants with combined hypertension and albuminuria compared to those who have neither condition.MethodsThe study included 24 South African cases with both hypertension and albuminuria and 49 control participants who had neither condition. Protein was extracted from urine samples and analysed using ultra-high-performance liquid chromatography coupled with mass spectrometry. Data were generated using data-independent acquisition (DIA) and processed using Spectronaut™ 15. Statistical and functional data annotation were performed on Perseus and Cytoscape to identify and annotate differentially abundant proteins. Machine learning was applied to the dataset using the OmicLearn platform.ResultsOverall, a mean of 1,225 and 915 proteins were quantified in the control and case groups, respectively. Three hundred and thirty-two differentially abundant proteins were constructed into a network. Pathways associated with these differentially abundant proteins included the immune system (q-value [false discovery rate] = 1.4 × 10− 45), innate immune system (q = 1.1 × 10− 32), extracellular matrix (ECM) organisation (q = 0.03) and activation of matrix metalloproteinases (q = 0.04). Proteins with high disease scores (76–100% confidence) for both hypertension and chronic kidney disease included angiotensinogen (AGT), albumin (ALB), apolipoprotein L1 (APOL1), and uromodulin (UMOD). A machine learning approach was able to identify a set of 20 proteins, differentiating between cases and controls.ConclusionsThe urinary proteomic data combined with the machine learning approach was able to classify disease status and identify proteins and pathways associated with hypertension-associated albuminuria.

Accelerated death of megakaryocytes from Wiskott-Aldrich syndrome patients.

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder caused by WAS gene mutations resulting in haematopoietic/immune cell defects. Recent studies report accelerated death of WAS platelets and lymphocytes. Data on megakaryocyte (MK) maturation, viability and their possible role in thrombocytopenia development in WAS are limited. In this study we evaluate the MK viability and morphology in untreated, romiplostim-treated WAS patients compared with normal controls. The study included 32 WAS patients and 17 healthy donors. MKs were captured from bone marrow aspirates by surface-immobilized anti-GPIIb-IIIa antibody. Viability (by phosphatidylserine [PS] externalization), distribution by maturation stages and size of MK were determined by light microscopy. MK distribution by maturation stages in patients differed from controls. 40 ± 22% of WAS MKs versus 23 ± 11% of normal MKs were at maturation stage 3 (p = 0.02), whereas 24 ± 20% in WAS and 39 ± 14% in controls had megakaryoblast morphology (p = 0.05). Romiplostim treatment changed the MK maturation stages distribution close to normal. PS-positive (PS+) MK in WAS was significantly higher (21 ± 21%) than in healthy controls (2 ± 4%, p < 0.01). WAS patients with more damaging truncating mutations and higher disease score had higher PS+ MK fraction (Spearman r = 0.6, p < 0.003). We conclude that WAS MKs have increased cell death tendency and changes in maturation pattern. Both could contribute to thrombocytopenia in WAS patients.

Human gut commensals support development of ocular autoimmunity in retina-specific T cell receptor transgenic mice

Abstract Autoimmune uveitis is a major cause of blindness, in which intraocular inflammation is driven by T cells that target the neuroretina. In a mouse model of spontaneous autoimmune uveitis (R161H), retina-specific T cells are primed in the gut through their transgenic TCR, and trigger disease. To support the relevance to human disease, we examined the development of uveitis and its association with gut microbiota in gnotobiotic R161H mice colonized with gut flora from healthy human donors. We then performed fecal metagenomic sequencing, gut immunophenotyping by flow cytometry and disease monitoring. Our results indicate that human gut commensals support development of autoimmunity in the spontaneous uveitis model. Human flora mice compared to SPF mice harboring normal mouse flora displayed altered intestinal effector and regulatory CD4 T cell profiles, and had decreased fecal metabolites including microbe-derived short chain fatty acids. Microbiome analyses showed that human flora mice retained a distinct but simplified gut microbial community compared to their original donor sample. Mice with high disease scores appeared to harbor more diverse gut flora than those with low scores. Verrucomicrobia, Actinobacteria, and Fusobacteria were enriched in mice with high disease scores, whereas Firmicutes appeared enriched in mice with low disease scores. In-vivo association studies are underway to examine the ability of candidate microbes to modulate autoimmune uveitis. These findings suggest that some taxa of human commensals may have enhancing or suppressive effects on the development of ocular autoimmunity. These candidate microbes can be explored as targets or as probiotics for therapeutic use.

ARYL HYDROCARBON RECEPTOR REGULATES GENES IN COLONIC EPITHELIAL CELLS TO MITIGATE COLITIS SEVERITY IN THE DSS-INDUCED MURINE MODEL

Abstract Current treatment of ulcerative colitis (UC) leaves a clear unmet need to target the colonic epithelial cells (CECs). In our previous study we found that aryl hydrocarbon receptor (AhR) expression on CECs has a vital role during indole-3-carbinol (I3C)-mediated protection against colitis. However, the precise mechanism behind this remains unclear. We investigated how intestinal regulatory components were altered in the absence or presence of AhR in CECs during I3C treatment under colitis (mouse model) or colitis-like conditions (colonic organoid). We generated conditional AhR-CEC knockout mice (AV) and induced colitis using the dextran sodium sulfate (DSS) model. Our results showed that the AV mice lost the protective effects of I3C against colitis. AV mice had higher disease scores and increased inflammation compared to controls. I3C treated AV mice that had DSS induced colitis were not able to regulate the colitis-associated parameters, even though flow cytometry analysis revealed AV mice were still capable of increasing protective interleukin-22 (IL-22) production in the colon. These results prompted us to study the CEC-specific mechanism involved in I3C-mediated protection against colitis. Whole transcriptome analysis of RNA isolated from enriched CECs of experimental mice was performed and results showed significant altered expression of several microRNAs, mucins (muc2 and muc13), and tight junction proteins (Cld3 and Cld4) in AV mice when compared to controls. RT-PCR data and direct effects of I3C on CECs (immunostaining) using organoids validated these results. This data concluded that AhR-dependent signaling orchestrates I3C-mediated protection of colitis. NIH 5P20GM103641

Aplikasi Sistem Pakar Berbasis Android dengan Metode Certainty Factor untuk Mendiagnosis Penyakit pada Tanaman Karet

Rubber is an important plantation commodity as a source of income, employment and foreign exchange opportunities, as an engine of economic development in new centers within the rubber plantation environment. Rubber plant diseases generally cause economic losses to rubber plantations. Lack of knowledge of farmers to control rubber plant diseases can result in losses and ultimately reduce farmers' income. Therefore, it is necessary to build a system that can diagnose diseases like an expert or an expert. The method used in this system is the certainty factor method which is used to prove whether a fact is certain or uncertain. This method is very suitable for expert systems that diagnose uncertainty. After that, a system validity test is carried out which aims to test the ability of the expert system to identify diseases. Based on the test results, the highest disease score was tapping groove disease with a disease percentage of 94.96%, while the lowest disease percentage was red root fungus disease with a percentage of 79%, with an average test result above 75% so that it was concluded that the system can diagnose rubber plant diseases well in accordance with the results of the diagnosis obtained.

PO49 Presentation Time: 10:00 AM: Prevalence of QTc Prolongation in Prostate Cancer Patients Undergoing Brachytherapy

<h3>Purpose</h3> QTc has been associated not only with a higher risk of Torsade de Pointes (TdP), sudden cardiac arrest but also with general cardiac mortality, including cardiovascular and coronary death. We examined the prevalence of prolonged QTc interval in prostate cancer patients undergoing brachytherapy in general and in patients with more aggressive cancers who may be exposed to ADT and compared them to patients who underwent prostatectomy. <h3>Materials and Methods</h3> We randomly selected 1094 patients treated with either low-dose rate (LDR) or high-dose rate (HDR) brachytherapy between August 2010 and February 2022 from our internal database. All patients had an ECG as part of the preoperative work-up. The QTc was automatically calculated using the Bazett formula. Excluded were patients with left or complete bundle branch block, ventricular extrasystoles, atrial fibrillation, presence of a pacemaker or a QRS ≥ 120 ms. .As primary outcome, a QTc ≥450ms was considered abnormal. Chi-square or Fisher's exact test, when appropriate was used to compare groups. Pearson correlation coefficient and binary multivariable regression analysis was used to evaluate correlations between QTc and clinical values. <h3>Results</h3> A total of 6.2% (n=68) had a QTc ≥450ms. Patients with a Cancer of the Prostate Risk Assessment (CAPRA) high risk disease (score 6-10) were significantly more likely to have a QTc ≥450ms than patients with low-or intermediate risk (9.7% vs. 5.5%, p=0.039). QTc as a continuous variable correlated weakly with the neutrophil count (r=0.13, p<0.001), age (r=0.08, p=0.009) and inversely with testosterone (r=-0.17, p=0.002). On binary multivariable regression analysis including neutrophils, testosterone and age, only testosterone [nmol/L] was predictive of a QTc ≥450ms, OR 0.9, 95% CI 0.82-0.98, p=0.02. We then compared the patients treated with brachytherapy to 178 patients who underwent prostatectomy. The latter had a non-significantly smaller portion of patient with a QTc ≥450ms: 4.5% vs. 6.2%, p=0.5. <h3>Conclusions</h3> Our data show that about 10% of patients with high-risk prostate cancer are at increased risk of TdP. Treating physicians should be aware of this and monitor the QTc during ADT to possible decrease cardiac mortality in these patients who require ADT. The correlation between increasing age, neutrophil count and low testosterone with QTc prolongation links inflammation and hypogonadism.

I3C-MEDIATED PROTECTION AGAINST COLITIS DEPENDENT ON AHR EXPRESSION ON VIL1-EXPRESSING COLONIC EPITHELIAL CELLS

Abstract Many current treatments for ulcerative colitis (UC) often causes side effects warranting safe therapeutic strategies to control the pathogenesis of colitis. Current study was aimed to ascertain the possible role of aryl hydrocarbon receptor (AhR) in vil1-expressing colonic epithelial cells (CECs) during I3C-mediated protection against colitis. We investigated how intestinal regulatory mediators were altered in the absence or presence of AhR in CECs during I3C treatment under colitis or colitis-like conditions. We generated conditional AhR knockout mice in vil1-expressing CECs using the cre-flox system and induced colitis using the dextran sodium sulfate (DSS) model. Results showed that the mice with AhR deficiency in CECs (AV mice) lost the protective effects of I3C treatment during colitis and had a higher disease score with increased inflammation in the colon compared to the controls. Also, after treatment with I3C during DSS-induced colitis, AV mice were not able to prevent colitis-associated gut microbial dysbiosis even though flow cytometry analysis revealed AV mice were still capable of increasing IL-22 production by ILC3s in the colon. IL-22-ILC3 immune cell response was not the only major mechanism involved in I3C-mediated protection against colitis and regulation of the gut microbiome. Transcriptome analysis of RNA isolated from enriched CECs of experimental mice showed significant altered expression of several microRNAs, mucins (muc3 and muc13), and tight junction proteins in AV mice compared to controls. PCR gene expression data and direct effects of I3C on CECs using colonic organoids validated these results. In summary, AhR expression in CECs play a critical role in I3C-mediated prevention of colitis.

AHR EXPRESSION ON VIL1-EXPRESSING COLONIC EPITHELIAL CELLS IS ESSENTIAL FOR I3C-MEDIATED PROTECTION AGAINST COLITIS

Abstract Ulcerative colitis (UC) is a chronic, idiopathic inflammatory disease that affects the colon and is characterized by localized tissue injury and disruption of the intestinal epithelial barrier. Pathophysiology of UC includes genetic predisposition, epithelial barrier defects, dysregulated immune responses, microbial dysbiosis, and environmental factors. Several therapeutic interventions for colitis have been identified, but many current treatments have various negative side effects, which is alarming given the incidence of UC is increasing around the world. Thus a search for safe therapeutic strategies to control the pathogenesis of colitis is still greatly needed. Previous studies from our laboratory reported that indole-3-carbinol (I3C), a natural plant product and ligand for the aryl hydrocarbon receptor (AhR), exhibited protective effects against colitis through innate lymphoid type 3 (ILC3) cells in an interleukin-22 (IL-22) dependent manner. The aim of this study was to ascertain the possible role of AhR in vil1-expressing colonic epithelial cells (CECs) during I3C-mediated protection against colitis. Using in vivo mouse studies and in vitro primary CEC organoid cultures, we investigated how key intestinal regulatory mediators (e.g. mucins and anti-microbial peptides, or AMPs) were altered in the absence or presence of AhR in CECs during I3C treatment under colitis or colitis-like conditions. We generated conditional AhR knockout mice in vil1-expressing CECs using the cre-flox system and induced colitis using the dextran sodium sulfate (DSS) model. Our results showed that the mice with AhR deficiency in CECs (AV mice) lost the protective effects of I3C treatment during colitis. Results showed that AV mice had a higher disease score and increased inflammation in the colon when compared to wild type (WT) or littermate (LM) controls. In addition, after treatment with I3C during DSS-induced colitis, AV mice were not able to prevent colitis-associated gut microbial dysbiosis even though flow cytometry analysis revealed AV mice were still capable of increasing IL-22 production by ILC3s in the colon. This suggested that the IL-22-ILC3 immune cell response was not the only major mechanism involved in I3C-mediated protection against colitis and regulation of the gut microbiome. Whole transcriptome analysis of RNA isolated from enriched CECs of experimental mice was performed and results showed significant altered expression of several microRNAs, mucins (muc3 and muc13), and tight junction proteins in AV mice when compared to wild type (WT) or littermate (LM) controls. PCR gene expression data and direct effects of I3C on CECs using colonic organoids from WT and AV mice validated these results. Collectively, these data showed that AhR expression in CECs play a critical role in I3C-mediated prevention of colitis.

AHR EXPRESSION ON VIL1-EXPRESSING COLONIC EPITHELIAL CELLS IS ESSENTIAL FOR I3C-MEDIATED PROTECTION AGAINST COLITIS

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory disease that affects the colon and is characterized by localized tissue injury and disruption of the intestinal epithelial barrier. Pathophysiology of UC includes genetic predisposition, epithelial barrier defects, dysregulated immune responses, microbial dysbiosis, and environmental factors. Several therapeutic interventions for colitis have been identified, but many current treatments have various negative side effects, which is alarming given the incidence of UC is increasing around the world. Thus a search for safe therapeutic strategies to control the pathogenesis of colitis is still greatly needed. Previous studies from our laboratory reported that indole-3-carbinol (I3C), a natural plant product and ligand for the aryl hydrocarbon receptor (AhR), exhibited protective effects against colitis through innate lymphoid type 3 (ILC3) cells in an interleukin-22 (IL-22) dependent manner. The aim of this study was to ascertain the possible role of AhR in vil1-expressing colonic epithelial cells (CECs) during I3C-mediated protection against colitis. Using in vivo mouse studies and in vitro primary CEC organoid cultures, we investigated how key intestinal regulatory mediators (e.g. mucins and anti-microbial peptides, or AMPs) were altered in the absence or presence of AhR in CECs during I3C treatment under colitis or colitis-like conditions. We generated conditional AhR knockout mice in vil1-expressing CECs using the cre-flox system and induced colitis using the dextran sodium sulfate (DSS) model. Our results showed that the mice with AhR deficiency in CECs (AV mice) lost the protective effects of I3C treatment during colitis. Results showed that AV mice had a higher disease score and increased inflammation in the colon when compared to wild type (WT) or littermate (LM) controls. In addition, after treatment with I3C during DSS-induced colitis, AV mice were not able to prevent colitis-associated gut microbial dysbiosis even though flow cytometry analysis revealed AV mice were still capable of increasing IL-22 production by ILC3s in the colon. This suggested that the IL-22-ILC3 immune cell response was not the only major mechanism involved in I3C-mediated protection against colitis and regulation of the gut microbiome. Whole transcriptome analysis of RNA isolated from enriched CECs of experimental mice was performed and results showed significant altered expression of several microRNAs, mucins (muc3 and muc13), and tight junction proteins in AV mice when compared to wild type (WT) or littermate (LM) controls. PCR gene expression data and direct effects of I3C on CECs using colonic organoids from WT and AV mice validated these results. Collectively, these data showed that AhR expression in CECs play a critical role in I3C-mediated prevention of colitis.

Easix before Conditioning Therapy Predicts Sepsis after Allogeneic Stem Cell Transplantation

Purpose: Endothelial complications are principal causes of non-relapse mortality (NRM) after allogeneic stem cell transplantation (alloSCT). Sepsis is a dysfunctional endothelial response to harmful microorganisms with increased risk of microvascular damage and organ failure. We hypothesized that the endothelial activation and stress index (EASIX) predicts risk of sepsis after alloSCT.Methods: In this retrospective evaluation, 1290 patients (random 1:1 allocation into a training cohort and a validation cohort while balancing for sepsis events) were assessed for presence of neutropenic fever, sepsis and infectious pathogens within 50 days after alloSCT. Sepsis and septic shock were defined according to the modified Sepsis-3 guidelines by the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO) for neutropenic cancer patients. EASIX and additional serum markers were assessed longitudinally before and after transplantation and correlated with outcome. Established clinical risk scores (EBMT, HCT-CI and VOD-CIBMTR) were raised and compared to EASIX.Results: Within the full cohort of 1290 patients transplanted since 01/2004, neutropenic fever episodes until day+50 after alloSCT were reported in 989 (76.7%), sepsis in 93 (7.2%), catecholamine use in 35 (2.7%), and mechanical ventilation in 31 (2.4%) patients. Patients who developed sepsis until day+50 differed from patients without early sepsis in more frequently having a higher disease score (58% vs 33%, p<0.001), more often receiving ATG prophylaxis (77% vs 64%, p=0.007), myeloablative or aplasia conditioning (44% vs 20%, p<0.001), and less likely receiving MTX prophylaxis (33% vs 43%, p=0.06).Prior to conditioning therapy, EASIX(-pre) was the only marker to predict the hazard of early sepsis irrespective of pathogen detection in time-dependent ROC (AUC 0.85 at day 50) and multivariable cause-specific Cox regression analyses (HR per two-fold increase 2.3 (1.9-2.8, p<0.001). The prognostic value of uni- and multivariable models were evaluated in the second cohort. An optimized cutoff for EASIX defined in the training cohort (2.32) strongly predicted sepsis in multivariable cause-specific Cox regression in the second cohort (HR 16.3 (7.0-37.5), p<0.001). Although Ferritin significantly predicted time to death without sepsis (HR per two-fold increase 1.11 (1.03-1.19), p=0.008), EASIX performed superior to other scores in univariate analysis when predicting time to early sepsis with respect to predictive accuracy measured by the time-dependent Brier score (Figure 1). Accordingly, EASIX was the strongest pre-transplantation score to predict early non-relapse mortality (NRM) within 6 months after alloSCT.Pre-conditioning leukocyte counts, CRP or endothelial serum markers did not associate with early sepsis. After transplantation starting with day 0, sepsis associated with EASIX at any time point until day+28, and in addition with suppressor of tumorigenicity (ST)2 and interleukin-18.Conclusions: EASIX is a powerful predictor of early sepsis and 6-months NRM, irrespective of detected pathogens. Patients with EASIX-pre>2.32 represent a high-risk cohort requiring intensive prophylaxis and endothelial protective treatment strategies. [Display omitted] DisclosuresSchönland: Pfizer: Honoraria; Janssen: Honoraria, Other: Travel grants, Research Funding; Prothena: Honoraria, Other: Travel grants; Sanofi: Research Funding; Takeda: Honoraria, Other: Travel grants. Hegenbart: Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Research Funding; Alnylam: Honoraria; Akcea: Honoraria; Prothena: Research Funding. Schmitt: Apogenix: Research Funding; Hexal: Other: Travel grants, Research Funding; Novartis: Other: Travel grants, Research Funding; Kite Gilead: Other: Travel grants; Bluebird Bio: Other: Travel grants; MSD: Membership on an entity's Board of Directors or advisory committees; TolerogenixX: Current holder of individual stocks in a privately-held company. Dreger: Novartis: Consultancy, Speakers Bureau; Bluebird Bio: Consultancy; Janssen: Consultancy; Gilead Sciences: Consultancy, Speakers Bureau; BMS: Consultancy; AbbVie: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau.

↵​Study of Morpho-physiological and Biochemical Traits for Resistance to Yellow Mosaic Virus (YMV) in Blackgram [Vigna mungo (L.) Hepper] Varieties

Background: Blackgram is one of the most important pulse crop in India and it is being affected by a number of insect pests from seedling stage to maturity. Among them whitefly is an important insect pest that transmit the viral disease, yellow mosaic virus (YMV), which is a major disease resulting in severe yield losses accounting for about 70% and infection at early stages may result in complete failure of the crop causing huge loss to the farmers economically. To overcome the losses due to this important disease in blackgram, study of host plant resistance to whiteflies, thereby minimizing the losses due to YMV disease is of great importance. The trichome density plays an important role as a morphological anti-feedant which reduces the pest attack and subsequently lowers the disease incidence and the plants with high trichome density showed less YMV symptom. The morpho-physiological and biochemical traits play an important role in host plant resistance against YMV disease through insect vector resistance and hence, the study was undertaken. Mathods: A field experiment was conducted during rabi 2017-18 and 2018-19 at RARS, Lam, Guntur in a randomized block design with eight blackgram varieties and replicated thrice under receding soil moisture condition. The experiment was conducted using eight blackgram varieties (LBG 787, GBG 1, TBG 104, LBG 884, LBG 806, LBG 808, LBG 623 and LBG 752) obtained from RARS Lam, Guntur and the variety LBG 623 was considered as a susceptible check. The estimation of sugars, phenols, tannins, trichome density and SCMR was done at vegetative and reproductive stages of crop growth. Result: A significant variation was observed among the varieties for all the traits observed at vegetative and reproductive growth stages during both rabi 2017-18 and 2018-19. The total sugar content of the blackgram varieties varied from 25.16 to 49.82 mgg-1 FW; the leaf phenolic content values ranged from 10.26 to 23.55 mg g-1 FW and the tannins content of the dried leaf samples ranged from 0.014 to 0.052 mgg-1 DW. The trichome density of the blackgram varieties varied from 12.91 to 74.59/cm2 of leaf area and the SCMR values ranged from 24.21 to 55.17. Higher seed yield was recorded in the variety LBG 884 followed by GBG1 and the lower seed yield was recorded in the variety LBG 623 during rabi 2017-18 and 2018-19. The YMV resistant varieties showed relatively higher phenolic, tannins content and trichome density and lower total sugar content in the leaf. The total sugar content showed a significant negative correlation with the seed yield. The SCMR value was significantly lower in the susceptible varieties of blackgram with higher disease scores.

Exercise Habits of Armenians Before and After the Emergence of the COVID-19 Pandemic

The COVID-19 pandemic brought about a variety of changes in people’s lifestyles, including their exercise habits. This study examined changes in exercise habits in individuals of Armenian descent, before and after the emergence of COVID-19, to determine whether significant changes had occurred. Convenience sampling was used by distributing the study throughout Armenian organizations, culturally-relevant social media pages, websites, and email lists. Subjects were required to be at least 18 years of age and of Armenian descent. Survey data was collected between June and August of 2020 from 502 subjects on exercise history, health history, and anthropometry. Disease scores were assigned based on health status. Subjects with higher disease scores were 2.5 and 3.1 times more likely to not exercise prior to and after the pandemic, respectively, compared to subjects with lower disease scores (p&lt;0.001). However, there was no significant difference in change in exercise frequency after the emergence of the pandemic. Additionally, subjects who only exercised in the gym prior to COVID-19 were more likely to decrease their exercise frequency compared to subjects who did not exercise at the gym or did not solely exercise at the gym (p&lt;0.001). Clinicians should place greater emphasis on encouraging Armenian patients with high disease scores to exercise. Armenian patients should also be encouraged to diversify their exercise spaces beyond the gym in order to reduce the risk of decreasing exercise frequency in the event of gym closures due to unforeseen circumstances.

AhR expression on both Rorc-specific immune cells and Vil1-expressing colonic epithelial cells are essential for I3C-mediated protection against colitis

Abstract Colitis is an inflammatory bowel disease (IBD) characterized by dysregulation of the immune system. In our previous reports, we showed indole-3-carbinol (I3C), an aryl hydrocarbon receptor (AhR) ligand, was able to reduce colitis-induced disease severity in an interleukin-22 (IL-22) dependent manner, mainly though innate lymphoid type 3 (ILC3) cells. In the current study, we generated cell-specific conditional knockout (KO) mice that had AhR deficiency in either Rorc-expressing immune cells (ILC3s), or Vil1-expressing colonic epithelial cells (CECs). We induced colitis using the dextran sodium sulfate (DSS) model in control mice and conditional KO strains, those deficient of AhR in Rorc (AR mice) or Vil1 (AV mice) cells. Results showed that compared to control mice, both AR and AV mice lost the expected efficacy effects of I3C treatment during colitis, with higher disease score and inflammation in the colon. Interestingly, immune cell profiling by single-cell RNAseq and flow cytometry showed only AR mice lost the ability to increase IL-22 secretion by ILC3s after I3C treatment during colitis. Since AV mice were still able to increase IL-22 via ILC3s, this suggests AhR deficiency in the CECs leads to alterations in other I3C-mediated mechanisms used to prevent colitis development, independent of the IL22-ILC3 axis. Collectively these data show AhR expression in both specific immune cells and CECs play a pivotal role in I3C-mediated prevention of colitis, though their mechanisms differ.

Morpho-physiological and Biochemical Variability in Greengram [Vigna radiata (L.) Wilczek] Varieties for Mungbean Yellow Mosaic Virus (MYMV) Resistance under Natural Field Conditions

Background: Mungbean yellow mosaic virus (MYMV) is economically most important disease of greengram reducing grain yields by 20-70%. Whiteflies and thrips are the most important insect pests which transmit the viral diseases MYMV and LCV respectively. The host plant resistance to MYMV disease in greengram genotypes has a great importance. The morpho-physiological and biochemical traits play an important role in host plant resistance against MYMV disease through insect vector resistance.Methods: A field experiment was conducted during rabi 2017-18 and 2018-19 at RARS Lam Guntur in a randomized block design with eight greengram genotypes and replicated thrice under receding soil moisture condition. The experiment was conducted using eight greengram varieties (WGG 42, Pusa Vishal, LGG 607, LGG 630, LGG 601, LGG 610, LGG 460 and LGG 450) obtained from RARS Lam Guntur and the genotype LGG 450 was considered as a susceptible check. The estimation of sugars, phenols, tannins, trichome density and SCMR was done at vegetative and reproductive stages of crop growth.Result: A significant variation was observed among the varieties for all the traits observed at vegetative and reproductive growth stages during both rabi 2017-18 and 2018-19. The total sugar content of the greengram varieties varied from 25.55 to 47.32 mgg-1 FW; the leaf phenolic content values ranged from 12.09 to 26.83 mg g-1 FW and the tannins content of the dried leaf samples ranged from 0.020 to 0.055 mgg-1 DW. The Trichome density of the greengram varieties varied from 75 to 162/cm2 of leaf area and the SCMR values ranged from 35.12 to 58.67. Higher seed yield was recorded in the variety LGG 630 followed by WGG 42 and the lower seed yield was recorded in the variety LGG 450 during rabi 2017-18 and 2018-19. The MYMV resistant varieties showed relatively higher phenolic, tannins content and trichome density and lower total sugar content in the leaf. The total sugar content showed a significant negative correlation with the seed yield. The SCMR value was significantly lower in the susceptible varieties of greengram with higher disease scores.

Caveolin-1 protects against DSS-induced colitis through inhibiting intestinal nitrosative stress and mucosal barrier damage in mice

Caveolin-1 (Cav-1) is a multifunctional protein and critical for the production of nitric oxide (NO) in intestinal physiological and pathological conditions, but its role in the inflammatory bowel disease(IBD) are still controversial. In this study we tested the hypothesis that Cav-1 could be an important cellular defense against IBD through inhibiting nitrosative stress and mucosal barrier damage. Male wild-type mice and Cav-1 knockout (Cav-1-/-) mice were subjected to 3% dextran sodium sulfate(DSS) for 7d to establish the experimental colitis model. A representative iNOS inhibitor (1400 W) was adopted to suppress the activity of iNOS in parallel group. Body weight and disease activity index were monitored. The colon tissues were evaluated through histological analysis. We found Cav-1 was down-regulated in the colon tissue and accompanied with the increase of iNOS and NO levels after DSS administration. Cav-1-/- mice were greatly increased susceptibility to DSS-induced colitis with the more weight loss and higher disease score than WT mice. Ablation of Cav-1gene significantly resulted in RNS overproduction, tight junctions impaired and inflammation elevated, which aggravated the severity of the intestinal damages. Furthermore, pharmacologic inhibition of iNOS by 1400 W significantly attenuated DSS-induced colitis in both WT and Cav-1-/- groups. Our results revealed an important role of Cav-1 in preventing intestinal nitrosative stress and mucosal barrier damage in the development of DSS-induced colitis.

Determination of fusarium crown rot resistance in wheat to Fusarium culmorum and Fusarium pseudogramineaum using real time PCR

Wheat varieties from Turkey, Australia and the Pacific Northwest of the US were screened for resistance to Fusarium crown rot (Fusarium pseudograminearum and Fusarium culmorum) in inoculated growth chamber studies. Fungal DNA was also quantified from the lower stems (crowns) of seedlings using quantitative PCR and crown rot scores were correlated with DNA results. There were significant differences among the varieties for crown rot severity index (p = 0.0265), crown rot score (p = 0.0003), disease index on leaf sheaths (leaf sheath score) (p = 0.0013), lesion length (p = 0.0200), and plant height (p < 0.0001). The crown rot score and plant height measurements also showed that the isolate of F. culmorum was more virulent than the isolate of F. pseudograminearum. The correlations were strongest between crown rot score and DNA levels at the second harvest, and much stronger with the isolate of F. culmorum compared to the isolate of F. pseudograminearum. Some susceptible varieties such as Seri had both a high disease score and high quantities of DNA, with both F. culmorum and F. pseudograminearum. On the other hand, varieties such as Matt, Sunco and Otis showed intermediate to high crown rot scores in response to F. culmorum, but much lower levels of DNA than Seri. 2–49, Burbot-6 and CT000161, in response to F. culmorum, showed low levels of disease and low levels of DNA. In conclusion, there were examples of varieties that were resistant and tolerant (low levels of DNA and disease), resistant and intolerant (low quantities of DNA, but higher levels of disease) and susceptible and intolerant (high quantities of DNA and disease). Quantitative PCR in combination with classical phenotyping of resistance to Fusarium crown rot may provide a tool for distinguishing resistance and tolerance in breeding efforts.

Association of gut microbiota with spontaneous autoimmune uveitis studied by human flora reconstitution of germ-free mice

Abstract Autoimmune uveitis is a T cell driven, intraocular inflammation that affects the neuroretina and can lead to blindness. In a mouse model of spontaneous autoimmune uveitis (R161H), retina-specific T cells are primed in the gut through their TCR and trigger disease (PMID: 26287682). To support the relevance to human disease, we examined development of uveitis and its association with bacterial taxa in gnotobiotic R161H mice harboring human flora. Specifically, fecal samples from three healthy human donors were inoculated into germ-free R161H mice and their wild type (WT) littermates in separate isolators. Fecal pellets from reconstituted mice and their offspring were collected periodically and subjected to 16S amplicon sequencing. Uveitis scores were determined in R161H offspring by histology at termination of the experiment. Our results show that healthy human gut commensals can support uveitis in R161H mice, but to a lesser extent than native mouse flora from the NIH facility. Diversity analyses indicate that human flora-reconstituted mice retained a distinct but simplified gut microbial community compared to the original sample, and R161H mice tended to have a more complex microbiome profile than WT littermates. Among R161H offspring, mice with high disease scores appeared to harbor more diverse gut flora than those with low scores. Differentially abundant bacterial taxa were identified between mice with different disease scores, which may associate with intensity of autoreactive T cell activation and development of autoimmunity. R161H associated with human gut flora could provide a more translatable platform than mouse flora to explore microbial candidates and products that may modulate autoreactive T cells in uveitis.

Effect of Long-term Oral Steroids on Intraocular Pressure in Children With Autoimmune Hepatitis: a Prospective Cohort Study.

Topical corticosteroids are known to cause raised intraocular pressure (IOP). However, there is a scarcity of literature regarding systemic steroids-induced raised IOP in children. The authors aimed to evaluate the IOP in children with autoimmune hepatitis (AIH) receiving oral prednisone. In this prospective study, children (1 to 18 y) with newly diagnosed AIH who received oral prednisone (July 2016 to December 2017) were included. Comprehensive ophthalmic check-up, including visual acuity, IOP, slit-lamp, and fundus examinations were done before and at 1, 3, and 6 months of follow-up. IOP ≥20 mm Hg was considered raised IOP. Symptomatic raised IOP patients were managed with antiglaucoma medication with a tapering dose of prednisone. A total of 33 children (19 boys) with a median age of 11 (3 to 18) years were analyzed. Raised IOP was observed in 20 (61%) children (19 were moderate and 1 was high responder) at 1 month, 8 (24%) at 3 months, and 1 (3%) at 6 months of treatment. Patients who developed raised IOP had a more severe liver disease in terms of decompensation and low albumin and high pediatric end-stage liver disease scores at presentation. There was no correlation between IOP and starting and cumulative dose of steroids. On multivariate analysis, decompensation at presentation was significantly associated with raised IOP (P<0.001; odds ratio, 30; 95% confidence interval, 4.2-210.6). Raised IOP returned to normal with antiglaucoma medication along with prednisone tapering in all except one. Systemic corticosteroids in children with AIH carry a risk for IOP elevation, especially in decompensated liver disease. A periodic ophthalmic check-up is necessary for early recognition and intervention before irreversible vision loss.

Recognition of viral and self-antigens by TH1 and TH1/TH17 central memory cells in patients with multiple sclerosis reveals distinct roles in immune surveillance and relapses

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that is caused by autoreactive T cells and associated with viral infections. However, the phenotype of pathogenic T cells in peripheral blood remains to be defined, and how viruses promote MS is debated. We aimed to identify and characterize potentially pathogenic autoreactive T cells, as well as protective antiviral T cells, in patients with MS. We analyzed CD4+ helper T-cell subsets from peripheral blood or cerebrospinal fluid for cytokine production, gene expression, plasticity, homing potentials, and their reactivity to self-antigens and viral antigens in healthy subjects and patients with MS. Moreover, we monitored their frequencies in untreated and fingolimod- or natalizumab-treated patients with MS. TH1/TH17 central memory (TH1/TH17CM) cells were selectively increased in peripheral blood of patients with relapsing-remitting MS with a high disease score. TH1/TH17CM cells were closely related to conventional TH17cells but had more pathogenic features. In particular, they could shuttle between lymph nodes and the CNS and produced encephalitogenic cytokines. The cerebrospinal fluid of patients with active MS was enriched for CXCL10 and contained mainly CXCR3-expressing TH1 and TH1/TH17 subsets. However, while TH1 cells responded consistently to viruses, TH1/TH17CM cells reacted strongly with John Cunningham virus in healthy subjects but responded instead to myelin-derived self-antigens in patients with MS. Fingolimod and natalizumab therapies efficiently targeted autoreactive TH1/TH17CM cells but also blocked virus-specific TH1 cells. We propose that autoreactive TH1/TH17CM cells expand in patients with MS and promote relapses after bystander recruitment to the CNS, whereas TH1 cells performimmune surveillance. Thus the selective targeting of TH1/TH17cells could inhibit relapses without causing JohnCunningham virus-dependent progressive multifocal encephalomyelitis.