Β-glucan Research Articles

Lactobacillus plantarum dy-1 fermented barley extraction activates white adipocyte browning in high-fat diet-induced obese rats.

High-fat diet (HFD)-induced obesity is caused by the imbalance between energy intake and expenditure. Here, we studied the inhibitory effects of aqueous extracts of fermented barley with Lactobacillus plantarum dy-1 (LFBE) and beta-glucan (BGL) on the obesity induced by HFD. Both LFBE and BGL significantly decreased body weight, suppressed visceral lipid accumulation, improved blood lipid profile, and glucose tolerance in HFD rats. BGL showed no thermogenic capacity, while LFBE enhanced the expression of Uncoupling Protein 1 (UCP1), and brown-specific mRNA (PRDM16, PGC1-α, and CIDEA) levels in brown adipose tissue (BAT) and white adipose tissues (WAT) of HFD rats. In addition, LFBE increased the expression of key genes involved in mitochondria biosynthesis and the mitochondrial respiration function. Further, we demonstrated that proteins extracted from LFBE (LFBE-P) were responsible for triggering brown markers to some extent. In conclusion, LFBE alleviates HFD-induced obesity by activating thermogenic fat bioenergetics and mitochondria biosynthesis. PRACTICAL APPLICATIONS: Barley is one of the most productive crops with pretty low utilization. Our group committed to exploring the application and nutritional value of barley. This work aimed to explore improvements in nutritional function of barley after fermentation by Lactobacillus plantarum dy-1. Our study found that oral administration of LFBE help turning white adipose tissue into a thermogenesis state and activate heat generation function of brown adipose tissue. Its characteristics mentioned above significantly inhibited the body weight and blood lipid of high-fat diet rats. Further, we evidenced that LFBE-P were responsible for triggering brown markers in 3T3-L1 cells. We believe our research plays a great part to relieving high-fat diet-induced obesity and type 2 diabetes with functional diet supplementation.

HYPOGLYCEMIC EFFECT OF FLAXSEED LIGNAN AND B GLUCAN IN POSTMENOPAUSAL DIABETIC PATIENTS

Diabetes mellitus is an important metabolic disorder and owing to its significant health impacts is a leading cause of death around the globe. According to WHO estimates, Pakistan is the 7th highest diabetes affected population of the world where almost 7 million peoples are suffering from the disease. Flaxseed lignan and beta glucan have constructive role in controlling diabetes. In connection to their enhanced insulin sensitivity, dietary supplementation of flaxseed fiber has shown potential results in postmenopausal diabetic women. The subject population was feed with lignan and beta glucan capsules and hypoglycemic activity was monitored both on daily and weekly basis. Blood samples was taken to observe the blood glucose by use of flaxseed lignan and β glucan in postmenopausal women. Fasting and random glucose levels of postmenopausal diabetic women in 4 weeks fed on flaxseed lignan and β glucan (P<0.01). Liver and kidney functioning tests are found to be non-significant. This research indicates that flaxseed lignan and β glucan reduces the random and fasting blood glucose levels in postmenopausal patients.

Chlorogenic acid and β-glucan from highland barley grain ameliorate β-cell dysfunction via inhibiting apoptosis and improving cell proliferation

Recent studies have reported that highland barley as a whole grain diet has anti-hyperglycemic effects, however little information is available about the active compounds that ameliorate pancreatic β-cell dysfunction and the related mechanisms. In this study, chlorogenic acid (CA) and β-glucan (BG) were identified as the active compounds that ameliorated β-cell dysfunction. CA ameliorated β-cell dysfunction by inhibiting cell apoptosis and improving glucose-stimulated insulin secretion via targeting G protein-coupled receptor 40 (GPR40) and regulating the phospholipase C β (PLCβ) pathway. BG ameliorated β-cell dysfunction by improving cell proliferation via targeting mammalian target of rapamycin (mTOR) and regulating the protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. Furthermore, CA and BG improved β-cell sensitivity and pancreatic insulin secretion, and inhibited β-cell apoptosis in impaired glucose tolerance (IGT) mice. Notably, CA restored homeostasis model assessment (HOMA)-β values and Ca2+-ATP and K+-ATP levels back to normal levels, and BG at 300 mg per kg BW restored β-cell insulin contents back to normal levels in IGT mice. Additionally, the combination of CA and BG had an additive effect on ameliorating β-cell dysfunction. These results help develop whole highland barley grain as a functional food for preventing type 2 diabetes by ameliorating pancreatic β-cell damage.

90. Incidence and Risk Factors for Inappropriate Use of Non-culture Based Fungal Assays: Implication for Diagnostic Stewardship

BackgroundCulture-based diagnostic tests are the gold standard for diagnosing invasive fungal diseases (IFDs). Because these tests have low sensitivity, non-culture-based fungal assays (NCBFAs) have been used increasingly to help diagnose IFDs. However, little is known about inappropriate use of NCBFAs. We aimed to investigate inappropriate use of NCBFAs in a tertiary academic hospital in Tokyo, Japan.MethodsThis retrospective cohort study included all patients who underwent testing with beta-D glucan (BDG) between January and March 2018, or galactomannan antigen (GMA) or cryptococcal antigen (CRAG) between January and June 2018. Patients who had received hematopoietic stem cell or solid organ transplantations were excluded. Appropriateness was assessed according to the previously published study. We compared patients with appropriate and inappropriate use of NCBFAs. Risk factors for inappropriate use were evaluated using multivariate logistic regression analysis.ResultsOf 1,140 patients (BDG, 1,009; GMA 273; CRAG, 310) who underwent tests, 470 patients (BDG, 394; GMA, 138; CRAG, 164) were included in this study. Four hundred thirty-eight patients (93.2%) were aged 18 or older. About 80% of NCBFAs (BDG, 334 patients [74.8%]; GMA, 117 patients [74.8%]; CRAG, 146 patients [89.0%]) were deemed inappropriate. The factors associated with inappropriate NCBFAs use included specialties of ordering physicians, risk factors for fungal infections, and recommendation from infectious disease physicians (Table). Sixty-four patients (13.6%) underwent three inappropriate NCBFAs simultaneously. Furthermore, during the study period, 408 patients (35.8%) with inappropriate NCBFAs underwent the same assays repeatedly during the study period; 643 times for BDG, 163 times for GMA, and 192 times for CRAG.The Factors Associated with Inappropriate Use of Non-Culture Based Fungal Assays ConclusionWe found a large proportion of NCBFAs were deemed inappropriate and it was mostly driven by ordering physicians who generally care for transplant patients. Because inappropriate use of NCBFAs could lead to additional inappropriate tests and treatment with substantial costs to patients and health systems, diagnostic stewardship targeting NCBFAs is urgently needed.Disclosures All Authors: No reported disclosures

A school-aged boy with nephrotic syndrome with cough for one month and shortness of breath for half a month

A boy, aged 6 years and 11 months, was admitted due to nephrotic syndrome for 2 years, cough for 1 month, and shortness of breath for 15 days. The boy had a history of treatment with hormone and immunosuppressant. Chest CT after the onset of cough and shortness of breath showed diffuse ground-glass opacities in both lungs. Serum (1, 3)-beta-D glucan was tested positive, and the nucleic acid of cytomegalovirus was detected in respiratory secretions. After the anti-fungal and anti-viral treatment, the child improved temporarily but worsened again within a short period of time. Pneumocystis jirovecii was identified by Gomori's methenamine silver staining in bronchoalveolar lavage fluid. The child was diagnosed with severe pneumonia (Pneumocystis jirovecii and cytomegalovirus infection), acute respiratory distress syndrome, and nephrotic syndrome. After anti-infective therapy with sulfamethoxazole/trimethoprim and ganciclovir and respiratory support, the child still experienced progressive aggravation of dyspnea and tension pneumothorax, and extracorporeal membrane oxygenation (ECMO) was given on day 13 of invasive ventilation. Anti-infective therapy with sulfamethoxazole/trimethoprim, ganciclovir, and linezolid, anticoagulation therapy, sedation therapy, nutrition, and comprehensive management of the respiratory tract were given during ECMO. The child was successfully weaned from ECMO after 72 days, resulting in a length of hospital stay of 134 days. The child was followed up for 6 months after discharge, and there was a significant improvement on lung CT, without organ dysfunction. It is concluded that Pneumocystis jirovecii pneumonia is a potential lifethreatening infection for children with low immunity, and that ECMO can effectively improve the prognosis of children with severe respiratory distress syndrome.

Performance evaluation of β-glucan treated lean clay and efficacy of its choice as a sustainable alternative for ground improvement

The choice of eco-friendly materials for ground improvement is a necessary way forward for sustainable development. Adapting naturally available biopolymers will render the process of soil stabilization carbon neutral. An attempt has been made to use β-glucan a natural biopolymer for the stabilization of lean clay as a sustainable alternative with specific emphasis on comprehending the effect of confining stresses on lean clay through triaxial compression tests. A sequence of laboratory experiments was performed to examine the various physical and mechanical characteristics of β-glucan treated soil (BGTS). Micro-analysis through micrographs were used to understand the strengthening mechanism. Results of the study show that the deviatoric stress of 2% BGTS is 12 times higher than untreated soil (UTS). The micrographs from Scanning Electron Microscopy (SEM) and the results of the Nitrogen-based Brunauer Emmett Teller (N2-BET) analysis confirm the formation of new cementitious fibres and hydrogels within the soil matrix that tends to weld soil particles and reduce the pore spaces leading to an increase in strength. Hydraulic conductivity (HC) and compressibility reduced significantly with the biopolymer content and curing period. Results emphases that β-glucan is an efficient and sustainable alternative to the traditional stabilizers like cement, lime or bitumen.

Glucan rich nutrition does not increase gut translocation of beta-glucan.

(1-3)-b-D-glucan (BDG) is a fungal cell wall component and, in the absence of invasive fungal infection, a novel biomarker for microbial translocation of endogenous fungal products from the gastrointestinal tract into systemic circulation. However, its value as a marker of fungal translocation is limited by a concern that plant BDG-rich food influences blood BDG levels. We conducted a pilot clinical trial to evaluate the impact of a standardised oral BDG challenge on blood BDG levels in participants with and without elevated microbial translocation. We enrolled 14 participants including 8 with HIV infection, 2 with advanced liver cirrhosis, and 4 healthy controls. After obtaining a baseline blood sample, participants received a standardised milkshake containing high levels of BDG followed by serial blood samples up to 8hours after intake. The standardised oral BDG challenge approach did not change the blood BDG levels over time in all participants. We found consistently elevated blood BDG levels in one participant with advanced liver cirrhosis and a single person with HIV with a low CD4 count of 201cells/mm3 . Our findings indicate that BDG blood levels were not influenced by plant origin BDG-rich nutrition in PWH, people with advanced liver cirrhosis, or healthy controls. Future studies are needed to analyse gut mycobiota populations in individuals with elevated blood BDG levels.

Preliminary Results of a Response-Adapted Study of Ibrutinib and Isavuconazole with Temozolomide, Etoposide, Liposomal Doxorubicin, Dexamethasone, Rituximab (TEDDI-R) for Secondary CNS Lymphoma

Background: Secondary CNS B-cell lymphomas (SCNSL) are aggressive lymphomas with a very poor prognosis. Genetic subtypes of DLBCL with CNS tropism are enriched for chronic active B-cell receptor signaling and may respond to BTK inhibition (BTKi). CLL, MCL, and transformed lymphomas can also involve the CNS and are BTKi responsive. TEDDI-R achieves durable remissions in relapsed/refractory primary DLBCL of the CNS (PCNSL) but the profile of SCNSL tumors that are ibrutinib-responsive is unknown. We present preliminary results from a response-adapted trial of ibrutinib with TEDD-R in SCNSL. Methods: Pts with aggressive B-cell lymphomas with secondary CNS involvement are eligible if age ≥18 and adequate organ function. Pts must have relapsed after frontline therapy or can be untreated if brain parenchyma involved. Prior BTKi is allowed, but HIVinfection and EBV+ lymphomas are excluded. Baseline tests include brain MRI, FDG-PET brain and body, CSF with flow cytometry, Ommaya, and eye exam. Pts receive isavuconazole starting at 200mg BID x 3d prior to ibrutinib to prevent fungal infections associated with TEDDI-R and then 200mg daily unless ibrutinib stopped. Pts first receive ibrutinib 560mg daily x 14d in a window. If ≥20% reduction after ibrutinib, pts receive TEDDI-R for 4 cycles every 21d with IT cytarabine. Pts with <20% reduction after ibrutinib receive TEDD-R without ibrutinib for 4 cycles every 21d with IT cytarabine. No consolidation or maintenance is permitted. Surveillance for fungal infections includes chest CT after each cycle along with Beta-D glucan and aspergillus galactomannan in blood and CSF. Brain MRI and CT scans are performed after cycles 1, 2, and 4 to determine response. All remissions by MRI are confirmed with FDG-PET and CSF analysis. Surveillance brain MRI and CT scans are q3m for 1y, q4m x 1y, q6m x 1y, then annually. Results: 16 pts with a median age 67 (range 40-79) enrolled between June 2019 and July 2020. 15 (94%) pts had DLBCL comprising 9 (60%) non-GCB, 5 (33%) GCB, and 1 (7%) transformed from MZL. One pt had plasmablastic lymphoma. Eight (50%) pts had a MYC-rearrangement including 4 (25%) with both MYC and BCL2 or BCL6 rearrangements. Eight (50%) pts had isolated CNS disease and 8 (50%) had synchronous CNS and peripheral disease. All pts relapsed after a median of 2 (range 1-4) prior therapies and all (100%) pts received prior anthracycline. Seven pts (44%) had prior CNS prophylaxis and 8 pts (50%) had prior HD-MTX based salvage therapy. Toxicity was evaluated across 35 cycles. G3 and G4 neutropenia occurred in 49% and 29% of cycles, respectively, while febrile neutropenia occurred in 9% of cycles. The median (range) duration of neutropenia was 6 (1-13) days. Five (14%) cycles were complicated by ≥G3 infection, but no opportunistic infections (including Aspergillus) were observed. One pt developed a bacterial infection during cycle 1 and died. G3 and G4 thrombocytopenia occurred in 34% and 23% of cycles, respectively, and 1 pt developed G3 hematuria. G3 mucositis occurred in 9% of cycles and palmar-plantar-erythrodysesthesia led to dose reductions of liposomal doxorubicin in 5 (36%) pts. Of 15 pts who completed the 14d ibrutinib window and were evaluable, 8 (53%) were ibrutinib-responsive and 7 (47%) were ibrutinib-resistant (Figure 1). Clinical responses were concordant across anatomic compartments; of 8 pts with both CNS and peripheral disease, 5 (63%) responded to ibrutinib in both compartments while 3 (37%) did not respond in either compartment. All 8 ibrutinib responders had a non-GCB phenotype and six (75%) achieved CR. One died of treatment-related toxicity after a PR and 1 is still on therapy. Only two (29%) pts with ibrutinib-resistant tumors achieved PR and none have achieved CR. After a median follow-up of 5.1m, a landmark analysis starting after the ibrutinib window demonstrated the PFS for pts with ibrutinib-responsive compared to ibrutinib-resistant tumors was not reached vs. 0.9m (95% CI: 0.1-2m)(p=0.002)(Figure 2). Conclusions: Patients with SCNSL tumors that are ibrutinib-responsive achieve a high rate of complete response to TEDDI-R in both CNS and peripheral disease. Patients with tumors that are ibrutinib-resistant also respond poorly to TEDD-R. Toxicity is mainly hematologic, and no Aspergillus infections have occurred with the use of isavuconazole prophylaxis. Updated clinical results from this ongoing study (NCT03964090) and will be presented at the meeting. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: ibrutinib for use in secondary cns lymphoma as part of a clinical trial

Phase 1 Study of Escalating Doses of Ibrutinib and Temozolomide, Etoposide, Liposomal Doxorubicin, Dexamethasone, Rituximab (TEDDI-R) with Isavuconazole for Relapsed and Refractory Primary CNS Lymphoma

Background: Primary DLBCL of the CNS (PCNSL) relies on chronic active B-cell receptor (BCR) signaling. Ibrutinib targets BCR signaling through BTK inhibition (BTKi), which may also impair innate immunity. We showed that ibrutinib and temozolomide, etoposide, liposomal doxorubicin, dexamethasone, rituximab (TEDDI-R) induces durable remissions in relapsed/refractory PCNSL but 7 (39%) pts developed Aspergillus infections without fungal prophylaxis. Newer triazoles are effective against Aspergillus but inhibit ibrutinib clearance through CYP3A4. Isavuconazole has less effect on CYP3A4 and less hepatotoxicity than voriconazole. We hypothesized that ibrutinib and isavuconazole could be safely co-administered in TEDDI-R and ameliorate the risk of Aspergillus while maintaining efficacy. We studied escalating doses of ibrutinib in TEDDI-R with isavuconazole to determine the safety profile, ibrutinib PK, and clinical activity in relapsed/refractory PCNSL. Methods: Pts with relapsed/refractory PCNSL, age ≥18, ECOG PS ≤2, and adequate organ function were enrolled. Previous BTKi, HIV, EBV+, and pregnancy were excluded. Pts had baseline MRI brain, FDG-PET brain and body, Ommaya placed, CSF with flow cytometry, and eye exam. Isavuconazole 200mg BID x 3d started prior to ibrutinib then 200mg daily. Three dose levels of ibrutinib (280mg, 420mg, 560mg) were given continuously through each cycle. Pts received up to 6 cycles of TEDDI-R with IT cytarabine. No one received maintenance or consolidation. If a DLT occurred in the first 3 pts at a given ibrutinib dose level, 3 more pts were treated before escalating. Full safety and PK data was reviewed after two dose levels prior to escalating. An expansion of 10 pts was planned at the highest ibrutinib dose level to confirm safety and clinical activity. Surveillance for fungal infections included chest CT mid-cycle 1 and after each cycle along with Beta-D glucan and aspergillus galactomannan in blood and CSF. Brain MRI was performed after cycles 1, 2, 4, and 6 to determine response and screen for CNS Aspergillus. All remissions by MRI were confirmed with FDG-PET and CSF analysis. Surveillance brain MRI were q3m for 1y, q4m x 1y, q6m x 1y, then annually. Primary objective was to identify the highest dose of ibrutinib safely co-administered with isavuconazole in TEDDI-R that achieves adequate PK concentrations. Results: 13 relapsed/refractory PCNSL pts enrolled between 11/2018 and 06/2020. 10 (77%) pts were male and the median age was 65 (range 46-77), including 3 pts ≥age 70. 13 (100%) pts had prior high-dose MTX, and 2 (15%) pts had prior autologous stem cell transplant (ASCT). Three evaluable pts received ibrutinib 280mg, 3 pts received ibrutinib 420mg, and 6 pts received ibrutinib 560mg. One pt in the 280mg cohort was not evaluable. Toxicity was evaluated in 13 pts across 49 cycles and the toxicity was mainly hematologic. G3 and G4 neutropenia occurred in 45% and 37% of cycles, respectively, while febrile neutropenia occurred in 8% of cycles. The median (range) duration of neutropenia was 4.5 (1-12) days. One pt with prior ASCT stopped after 4 cycles due to myelosuppression. Four (8%) cycles were complicated by ≥G3 infection, but no opportunistic infections (including Aspergillus) were observed. G3 and G4 thrombocytopenia occurred in 22% and 8% of cycles, respectively, and 1 pt developed melena with no overt GI bleeding. ≥G3 mucositis occurred in 6% of cycles and 1 patient stopped therapy after 5 cycles due to recurrent mucositis. Palmar-plantar-erythrodysesthesia led to dose reductions of liposomal doxorubicin in 9 (69%) pts, but only 1 G3 event occurred. Twelve pts were evaluable for response, and 11 (92%) pts have responded and all after receiving only 1 cycle (Figure 1). All 8 (100%) pts who have completed at least 4 cycles have achieved CR and the other 4 remain on therapy. Six (75%) pts who achieved CR remain in remission while 2 (25%) pts relapsed within 3 months of stopping therapy. After a median potential f/u of 5.2 months, the 1-year PFS is estimated at 60.0% (95% CI, 12.6-88.2) and the OS is 100%. Conclusions: Ibrutinib 560mg was safely co-administered with isavuconazole in TEDDI-R for relapsed/refractory PCNSL. No DLTs were observed, no cases of Aspergillus occurred, and no new safety signals. The first 8 (100%) patients who have completed therapy achieved complete response. Updated clinical results from this ongoing study (NCT02203526) will be presented at the meeting. Disclosures Lai: Abbvie: Consultancy; Agios: Consultancy; Jazz: Speakers Bureau; Macrogenics: Consultancy; Astellas: Speakers Bureau.

Multiple B-D Glucan and Cmv Test Ordering By Multiple Physicians – Analysis To Assess The Frequency Of Duplicate Test Orders

Abstract Introduction/Objective In teaching hospitals, patients receive direct care from a succession of different physicians, each of whom may order diagnostic tests on the same patient resulting in multiple physicians unknowingly ordering the same test in the same time period, leading to overutilization. We examined the association of test-ordering by multiple physicians with duplication of two tests, Beta D-Glucan (BDG) and CMV Viral Load by PCR non blood, as aid for detection of fungal and cytomegaloviral infections, respectively Methods Retrospective medical records at Baylor University Medical Center, Dallas were examined in between 10/1/2019- 10/30/2019. A total 167 test orders were identified for CMV Viral Load non blood and BDG presence in blood. Each medical record was assessed for frequency of ordering along with the physicians who ordered them Results A total 167 tests were ordered in which, 120 times BDG was ordered and 52 times CMV was ordered. Singleton orders were noted in 85(50%) instances of BDG & 30(17%) for CMV.Multiple test orders were 44 (25%) for BDG and 8 (4%) for CMV respectively. Both CMV and BDG were ordered together 57 times. The time stamps of multiple test orders in individual patients was assessed for instances of orders that were less than 3 days apart and analysis showed out of the 44 multiple test orders, 34% (15) test orders were ordered less than 3 days apart and 66%(29) tests were ordered more than 3 days apart for BDG. Upon chart review, most of these quickly successive orders were by different physicians. The estimated costs of the duplicate orders are 4334.0$ & 1104.16$ for BDG and CMV respectively. Conclusion CMV and BDG are commonly ordered on many patients. Analysis shows that many times, physicians order testing when the same test has been ordered very recently by a separate physician. Note that for both tests, retesting in less than three days is not normally indicated, however this happens often, especially for BDG. This is most likely due to difficulty in determining within the EHR what tests are drawn and “pending’ but not yet finalized and reported. With usage of prompts/ alerts in EMR that warn of existing “pending’ orders by another caregiver, the frequency of duplicate test ordering for the same patient may be reduced, in turn reducing the costs of healthcare.

Genetic Variance of Metabolomic Features and Their Relationship With Malting Quality Traits in Spring Barley.

Barley is the most common source for malt to be used in brewing beer and other alcoholic beverages. This involves converting the starch of barley into fermentable sugars a process that involves malting, that is germinating of the grains, and mashing, which is an enzymatic process. Numerous metabolic processes are involved in germination, where distinct and time-dependent alterations at the metabolite levels happen. In this study, 2,628 plots of 565 spring malting barley lines from Nordic Seed A/S were investigated. Phenotypic records were available for six malting quality (MQ) traits: filtering speed (FS), wort clearness (WCL), extract yield (EY), wort color (WCO), beta glucan (BG), and wort viscosity (WV). Each line had a set of dense genomic markers. In addition, 24,018 metabolomic features (MFs) were obtained for each sample from nuclear magnetic resonance (NMR) spectra for wort samples produced from each experimental plot. The genetic variation in the MFs was investigated using a univariate model, and the relationship between MFs and the MQ traits was studied using a bivariate model. Results showed that a total of 8,604 MFs had heritability estimates significantly larger than 0 and for all MQ traits, there were genetic correlations with up to 86.77% and phenotypic correlations with up to 90.07% of the significant heritable MFs. In conclusion, around one third of all MFs were significantly heritable, among which a considerable proportion had significant additive genetic and/or phenotypic correlations with the MQ traits (WCO, WV, and BG) in spring barley. The results from this study indicate that many of the MFs are heritable and MFs have great potential to be used in breeding barley for high MQ.

Effects of β-glucan and Xanthan gum-based Biopolymers on Plant Growth and Competition in the Riverbank

Effects of β-glucan and Xanthan gum-based Biopolymers on Plant Growth and Competition in the Riverbank

THE TALE OF A HALO SIGN

SESSION TITLE: Fellows Imaging Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Halo sign on chest imaging is characterized by a circular area of ground-glass attenuation around a central pulmonary nodule or mass. It is most commonly associated with invasive fungal infections; however, can also be seen in a wide range of neoplastic and inflammatory conditions. Here we present a case of angio-invasive neoplasm presenting with characteristic halo sign in an immunocompromised patient. CASE PRESENTATION: A 62-year-old male with alcoholic cirrhosis post orthotopic liver transplant on chronic immunosuppression with recurrent cirrhosis of his graft liver was initially admitted for management of acute hepatic encephalopathy. A CT scan of his chest showed numerous part solid centrilobular nodules bilaterally with central solid component and surrounding ground glass halo. Invasive fungal infection was suspected, and micafungin was initiated. Serum aspergillus antigen and beta D-glucan were negative. He underwent bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB). BAL was negative for bacterial, fungal and acid-fast bacilli cultures. Pathology from the TBB showed atypical epithelioid cells that could be reactive or due to a metastatic disease. A repeat CT scan performed after 10 days of antifungal therapy showed a significant increase in size of the previously noted centrilobular nodules with surrounding ground glass halo. Surgical open lung biopsy was considered but he was deemed to be a poor surgical candidate due to his frailty and comorbidities. Transbronchial cryobiopsy was then performed which showed poorly differentiated epithelioid neoplasm predominantly within the vascular spaces. Based on immunohistochemical staining positive for both cytokeratin and vascular markers, a differential diagnosis of epithelioid angiosarcoma vs. epithelioid sarcoma was made. After detailed discussion with him and his family in regards to his overall prognosis, he wished for no further testing or interventions and chose to go home with hospice. DISCUSSION: Halo sign indicates presence of hemorrhagic nodules. It was first described in immunocompromised patients with invasive pulmonary aspergillosis where the nodule itself is a focus of pulmonary infarction with surrounding alveolar hemorrhage. However, it has now been associated with a variety of pulmonary diseases including both infectious and non-infectious hemorrhagic nodules, tumor cell infiltration and few non-hemorrhagic etiologies. Metastatic lung disease from hyper vascular tumors such as angiosarcoma, chondrosarcoma and melanoma can form a halo of ground glass attenuation as a result of peritumoral hemorrhage or infiltration. Malignancy is a leading cause of death in post liver transplant patients and should always be considered in the evaluation of these patients. CONCLUSIONS: While evaluating halo sign a wide differential should be considered including malignancy in a post liver transplant patient. Reference #1: Georgiadou SP, Sipsas NV, Marom EM, Kontoyiannis DP. The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts. Clin Infect Dis. 2011;52(9):1144-1155. doi:10.1093/cid/cir122 Reference #2: Parrón M, Torres I, Pardo M, Morales C, Navarro M, Martínez-Schmizcraft M. Signo del halo en la tomografía computarizada de tórax: diagnóstico diferencial con correlación anatomopatológica [The halo sign in computed tomography images: differential diagnosis and correlation with pathology findings]. Arch Bronconeumol. 2008;44(7):386-392. DISCLOSURES: No relevant relationships by Sadia Benzaquen, source=Web Response No relevant relationships by Ena Gupta, source=Web Response No relevant relationships by ATUL MATTA, source=Web Response No relevant relationships by Corrado Minimo, source=Web Response No relevant relationships by Carlos Oberto, source=Web Response

Yerel Yulaf (Avena sativa L.) Genotiplerinin Eskişehir Koşullarında Tane Verimi ve Bazı Kalite Özellikleri

Geçit Kuşağı Tarımsal Araştırma Enstitüsü Müdürlüğü (GKTAEM)‘ndeki yulaf ıslah çalışmaları 1929 yılından beri sürdürülmektedir. Bu çalışma kapsamında, bölge koşullarına uyumlu yerel yulaf hatlarından verimi ve kalitesi yüksek olanların seçilerek, yeni çeşit olarak tescil ettirilmesi hedeflenmiştir. Denemeler, 2017-2018 üretim yılında Eskişehir GKTAEM Merkez ve Hamidiye yerleşkelerinde yağmura bağımlı koşullarda yürütülmüş olup, bu çalışmada, ülkenin değişik yerlerinden toplanan 19 yerel hat ile standart olarak Checota, Kahraman, Kırklar, Yeniçeri ve Sebat çeşitleri kullanılmıştır. Bu araştırmada genotiplerde tane verimi (TV), bin tane ağırlığı (BTA), bitki boyu (BB), yatma değeri (YD), salkım çıkarma süresi (SÇS) gibi çeşitli agro-morfolojik özelliklerinin yanı sıra tane protein oranı (TPO) ve beta glukan oranı (BG), asit deterjan lif (ADF) ve nötral deterjan lif (NDF) değerleri incelenmiştir. Elde edilen bulgulara göre, ADF ve NDF değerleri dışındaki parametrelerde genotipler arası farklılıklar istatistiksel olarak önemli bulunmuş olup, TV (2,31 – 3,58 t ha-1) değerleri arasında ortalama olarak 2,93 t ha-1 hesaplanmış; genotiplerdeki BTA (25,5 – 37,1 g) arasında bulunmuş; BB ise (83,3 – 130,2 cm) olarak belirlenmiş; YD (%1 – 57) şeklinde notlanmış; SÇS (126,0 – 141,0 gün) şeklinde saptanmış; BG (%3,29 – 5,16) arasında değişmiş; TPO (%13,4 – 15,9) arasında olmuş; ADF ve NDF oranları sırayla, (%16,4 – 19,4) ile (%30,8 – 38,8) arasında belirlenmiştir. Buna göre, G13, G16, G19, G21, G22 ve G23 yerel yulaf hatlarının hedeflenen agro-morfolojik ve kalite özellikleri bakımından yeterli oldukları anlaşılarak ilgili ıslah programında bir üst kademeye aktarılması sağlanmıştır.

Conjugation of β-glucans on heat-stable enterotoxin (ST) to enhance the immunogenic response in mouse leucocytes.

Enterotoxigenic Escherichia coli (ETEC) is an important diarrhea-causing pathogen for humans. Heat-stable enterotoxin (ST) plays a crucial role in triggering diarrhea and ETEC pathogenesis. However, ST is a small peptide that lacks immunogenic activity itself but becomes immunogenic when it is coupled to a carrier molecule. In this study, the β-glucans (BG) from yeasts have been used to test their immunomodulatory activity and adjuvant effect on the properties of ST. This study aimed to synthesize and characterize a conjugate of yeast-derived β-glucan with the ST enterotoxin (BG-ST) and evaluate the antigenic and antioxidant activities in mouse splenocytes. Fourier transform infrared spectroscopy and scanning electron microscopy analysis showed new bands and changes in morphology, respectively, confirming ST was successfully coupled to beta glucan. Additionally, according to the enzyme-linked immunosorbent assay (ELISA), conjugation efficiency was almost 90%. Cellular viability, phagocytic cell proportion, and respiratory burst enhanced splenocytes stimulated by BG-ST. In addition, nitric oxide production and antioxidant enzymes increased in cells stimulated with BG-ST, BG and ST. In conclusion, the results revealed the successful conjugation of β-glucan with ST peptide enhancing immune and antioxidant parameters to a greater extent than their individual components.

Performance of the (1,3)-Beta-D-Glucan Assay on Bronchoalveolar Lavage Fluid for the Diagnosis of Invasive Pulmonary Aspergillosis.

Detection of (1,3)-beta-D-glucan (BDG), a component of the cell wall of many fungi, was studied in bronchoalveolar lavage fluid (BALF) as a possible aid for the diagnosis of proven/probable invasive pulmonary aspergillosis (IPA). BDG was measured on stored BALF from 13 patients with EORTC/MSGERC defined proven/probable IPA and 26 matched control patients without IPA. The median BALF BDG was 80pg/mL (range < 45-8240pg/mL) in the IPA cohort and 148pg/mL (range < 45-5460pg/mL) in the non-IPA cohort. Using a positive cutoff of ≥ 80pg/mL, sensitivity was 54% and specificity was 38%. Higher cutoff values led to improvement in specificity but a dramatic decrease in sensitivity. ROC/AUC analysis was unable to identify an optimal cutoff value at which test performance was enhanced: AUC 0.43, 95% CI 0.24-0.63. When the BDG assay was performed on BALF, neither sensitivity nor specificity was sufficient for use in the diagnosis of IPA.

Abstract CT073: IMPRIME 1 (NCT02981303): A novel phase 2 study in second-line +, metastatic triple negative breast cancer patients shows promising clinical benefit for the combination of the immune checkpoint inhibitor, pembrolizumab (pembro), with the novel innate immune activator, Imprime PGG

Abstract Background: Immune checkpoint inhibitor (ICI) monotherapy shows limited benefit in metastatic triple negative breast cancer (mTNBC) patients (pts), particularly in the second line + setting (ORR ~5-6%, mOS 9 months). In the recent Keynote-119 phase 3 study in 2 or 3L chemorefractory mTNBC pts, pembro monotherapy showed 9.9 month mOS, 9.6% ORR vs 10.8 month mOS, 10.6% ORR for physician's choice chemotherapy. Imprime PGG (Imprime) is a novel, systemically-delivered Beta Glucan agonist of the Dectin Receptor that activates the innate immune system to reprogram the immunosuppressive tumor microenvironment, activate antigen presenting cells and stimulate antigen-specific T cell activation. In preclinical models, Imprime significantly enhances the anti-cancer efficacy of ICI therapy. Accordingly, we sought to explore whether Imprime might enhance the clinical benefit of the ICI, pembro, in 2L+ mTNBC pts. Methods: IMPRIME 1 is an open-label, Simon 2 stage study (12 pts Stage 1, 32 pts Stage 2) with primary completion Dec. 2019. Pts received Imprime (4 mg/kg IV days 1, 8, 15 of each 3-week cycle) + pembro 200 mg on D1 of each cycle. CT scans were taken at baseline and q6wks thereafter until progression. Primary endpoints were ORR (RECIST v1.1) and safety. Secondary endpoints included PFS, OS. Biopsies and blood samples were collected to assess immune activation. Mechanistically, Imprime-mediated activation of innate immune cells requires anti-beta glucan antibodies (ABA). Enrollment was limited to patients having sufficient ABA IgG (≥20mcg/ml). Results Response and Disease Control Rates (Imprime 1 [95% CI]) Overall Response: 15.9% (7.9- 29.4) Stable Disease: 38.6% (25.7-53.4) Progressive Disease: 40.9% (27.7-55.6) Disease Control (CR+PR+SD): 54.5% (40.1-68.3) Disease Control (CR+PR+SD ≥24w): 25.0% (14.6- 39.4) Survival Median Overall Survival (months): 16.4 (11.1- 23.9) 12 Month Survival: 57.6% (42.4-72.8) 18 Month Survival: 36.7% (21.3-52.1) Clinical benefit was pronounced in mTNBC pts previously treated with endocrine therapy (originally ER/PR+ pts). Peripheral blood shows innate immune activation (e.g. increased CD86 on circulating monocytes) and CD8 T cell activation (PD1+/Ki67+/HLA-DR+) as early as 3 wks on therapy. These changes were associated with enhanced PFS and OS. Paired tumor biopsies showed robust infiltration of tumor tissue by activated myeloid cells (Imprime+/PD-L1+/CD80+) and activated CD4, CD8 T cells (Ki67+/granzyme B+). The combination was well-tolerated. Related Gr 3/4 AEs evident in 3/44 pts. The most common Infusion-related reactions were Gr1/2. Conclusion: IMPRIME 1 provides clinical and molecular/ cellular proof of concept data for the combination of Imprime and pembro. These promising data support additional clinical studies in mTNBC pts for this novel Immuno-onocology combination. Citation Format: Steven J. O'Day, Virginia F. Borges, Bartosz Chmielowski, Ruta D. Rao, Maysa Abu-Khalaf, Alison Stopeck, Joyce A. O'Shaughnessy, Michael Chisamore, Vassiliki Karantza, Joanna Cox, Paulette Mattson, Michele A. Gargano, Bruno Osterwalder, Mark Uhlik, Nandita Bose, Jeremy Graff. IMPRIME 1 (NCT02981303): A novel phase 2 study in second-line +, metastatic triple negative breast cancer patients shows promising clinical benefit for the combination of the immune checkpoint inhibitor, pembrolizumab (pembro), with the novel innate immune activator, Imprime PGG [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT073.

Formulations of Staphylococcus aureus bacteriophage in biodegradable beta-glucan and arabinogalactan-based matrices

Novel binary polysaccharide hydrogels and xerogels based on immunoactive beta-glucan (BG) or arabinogalactan (AG) and gums were prepared. The aim of this study was to prepare formulations ensuring viability of Staphylococcus aureus bacteriophage during storage conditions with a special focus to rapidly achieve a gelled state at moderate conditions. Bacteriophage was loaded to xerogels and pre-formulated by lyophilization resulting into phage hydrogels and dried to corresponding phage xerogels. The pre-formulation step allowed fast reconstitution of xerogels into hydrogels at mild conditions, thus preserving phage viability. Viability of the entrapped phage in AG and BG binary xerogels and corresponding hydrogels was tested after six months of storage at 4 °C. The phage xerogels were amorphous except hydroxypropyl methylcellulose-containing matrices. Phage viabilities above 99% were observed in the semi-crystalline formulations with a final survival of 9.21 log10 PFU/mL. The results show that the binary formulations improve phage protection and enable a large proportion of bacteriophage to remain active for extended period of time. The application areas of these formulations include topical phage therapy and nasal administration of phages with prolonged stability.

Carbon footprint and land use of food products containing oat protein concentrate

There is potential to reduce greenhouse gas emissions by reducing the intake of animal-based proteins. In western countries, the intake of proteins can usually simply be reduced, but substituting even only part of the intake of animal-based proteins with plant-based proteins would also benefit both human health and the environment.The aim of this study was to assess the environmental benefits of using protein-rich side streams from oat beta glucan processing as an ingredient in protein-enriched foods. The environmental impact of food products (bread, pasta, and oatgurt) containing oat protein concentrate (OPC) was assessed using Life Cycle Assessment methodology from cradle-to-processing. The environmental impact was compared with those of regular food products and existing plant protein sources as per kilogram of product (mass) and per kilogram of protein to assess the environmental benefits of novel products.All the ‘high in protein’ versions of foods containing OPC have a nearly equal carbon footprint per kg of protein, and all three products can be used as substitutes for commonly used pasta, bread, and yogurt in the diet. Thus, they all have similar potential to reduce food consumption greenhouse gas emissions. All the foods containing OPC also have very low land use per kg of product compared with the regular products. When products containing OPC are compared with other protein-rich food products, products containing OPC have a smaller carbon footprint per kg of protein compared with animal-based protein sources and a similar footprint with naturally protein-rich plant products like legumes.The potential to reduce the carbon footprint by substituting animal-based protein sources with novel foods containing plant protein concentrates looks promising in the light of these results, as long as the consumption of animal protein sources in the overall diet is reduced at the same time.

Changes in the Fecal Metabolome Are Associated with Feeding Fiber Not Health Status in Cats with Chronic Kidney Disease

The objective was to determine the effects of feeding different fiber sources to cats with chronic kidney disease (CKD) compared with healthy cats (both n = 10) on fecal metabolites. A cross-over within split-plot study design was performed using healthy and CKD cats (IRIS stage 1, 2, and 3). After cats were fed a complete and balanced dry food designed to aid in the management of renal disease for 14 days during a pre-trial period, they were randomly assigned to two fiber treatments for 4 weeks each. The treatment foods were formulated similar to pre-trial food and contained 0.500% betaine, 0.586% oat beta glucan, and either 0.407% short chain fructooligosaccharides (scFOS) fiber or 3.44% apple pomace. Both treatment foods had similar crude fiber (2.0 and 2.1% for scFOS and apple pomace, respectively) whereas soluble fiber was 0.8 and 1.6%, respectively. At baseline, CKD had very little impact on the fecal metabolome. After feeding both fiber sources, some fecal metabolite concentrations were significantly different compared with baseline. Many fecal uremic toxins decreased, although in healthy cats some increased; and some more so when feeding apple pomace compared with scFOS, e.g., hippurate, 4-hydroxyhippurate, and 4-methylcatechol sulfate; the latter was also increased in CKD cats. Changes in secondary bile acid concentrations were more numerous in healthy compared with CKD cats, and cats in both groups had greater increases in some secondary bile acids after consuming apple pomace compared with scFOS, e.g., tauroursodeoxycholate and hyocholate. Although changes associated with feeding fiber were more significant than changes associated with disease status, differential modulation of the gut-kidney axis using dietary fiber may benefit cats.