CS Treatment Research Articles

Hemoperfusion with CytoSorb® in Pediatric Patients: A Monocentric Case Series.

Background: Pro- and anti-inflammatory cytokines help regulate the inflammatory response. A cytokine storm is a dysregulated cytokine response associated with sepsis and other conditions that result in a hyper-inflammatory state. Extracorporeal cytokine adsorption has the potential to restore a balanced inflammatory response. Hemoperfusion with CytoSorb® (CS) appears to be a short-term mode of treatment of sepsis in both adults and children. Objective: We present a case series of eight critically ill children involving the use of hemoperfusion with CS at the University Medical Center Ljubljana to treat clinically manifested cytokine storm. Results: In our preliminary experience, it was applied without complication in five children weighing more than 10 kg, who all survived. The effect of age on complications regarding CS treatment is unclear, yet in our case series, all three patients weighing less than 10 kg died of their disease. Conclusions: In our preliminary experience, cytokine adsorption with CS remains a potential adjunctive treatment for cytokine storm in critically ill children.

A Rare Case of Tremor Induces by Cycloserine in Drug-Resistant Tuberculosis Patient

Background: Tuberculosis is a contagious disease that generated by Mycobacterium tuberculosis. Drug-Resistant tuberculosis (DR-TB) is inculpated the use of the second-line anti-tubercular treatment which is associated with many drug side effects or so called, Adverse Drug Reactions (ADR). Cycloserine (Cs) is an important drug against drug resistant tuberculosis (DR-TB). Cycloserine has been used in tuberculosis therapy since the late 1950s. Identical with most drug, Cycloserine can cause many Adverse Drug Reactions (ADR). Case Illustration: A 23-year-old woman diagnosed with drug-resistant tuberculosis is undergoing long-term treatment. The patient received treatment for DR-TB with the Bdq-Lfx-Cfz-Cs-E regimen. After the patient underwent the 10th month of advanced phase treatment, the patient complained of shaking in both hands (tremors). The tremor is felt to be more severe in the right hand and the patient cannot grip objects tightly. Discussion: Cycloserine (Cs) play an important role in second-line drug management of DR-TB. Cs-Induced psychosis and other neurological side-effects can be detrimental towards patients yet they are rarely reports in DR-TB cases. Cs is correlated with severe psychiatric cases and Central Nervous System related ADRs. Cs-associated ADR is most likely because of production of gamma-aminobutyric acid as a result of inhibition of glutamic decarboxylase. Study Shown that among 132 patients who reported side effects in the cycloserine group, 2 (1.4%) experienced major side effects, namely tremors. Side effects possibly or probably related to Cs appeared after a median of 71 days (range 10–331 days) of Cs treatment. Conclusion: the drug side effects such as tremors are very rare in drug-resistant tuberculosis patients. In this case, the patient's complaint of tremors could be caused by cycloserine as an anti-tuberculosis drug.

Does higher ratio of wheat straw addition decrease PAHs degradation in PAHs-contaminated paddy soils and PAHs concentrations in rice?

There are considerable studies focusing on impacts of straw returning on PAHs degradation and bioavailability in PAHs-contaminated upland soils, while similar research in paddy soils is limited. Incubation experiments and pot trials were conducted to study effects of straw returning on PAHs degradation in paddy soils and PAHs accumulation in rice, respectively. There are threshold effects of straw returning on PAHs degradation in PAHs-contaminated paddy soils. The inflection point of PAHs degrading was recorded under 0.8 % wheat straw treatment (conventional (CS) and pretreated wheat straw (PS)), which increased PAHs degradation by 18.13–32.36 %. The lowest PAHs concentrations in rice were recorded under 1 % straw (CS and PS) treatment, which was attributed to the highest PAHs degradation in rhizosphere soils. Compared to CS treatment, PS treatment significantly (p < 0.05) increased PAHs degradation by 7.93–10.28 % and PAHs concentrations in rice by 12.38–45.87 % due to that increasing dissolved organic carbon (DOC) enhanced PAHs concentrations in porewater of rhizosphere soils. Higher diversity enhanced the metabolic pathways and function genes to degrade PAHs by improving bacterial phenotypes and biochemical processes under 1 % wheat straw and PS treatment. The present study firstly demonstrated that the effects of straw returning on PAHs degradation in PAHs-contaminated paddy soils and PAHs concentrations in rice depended on amount and methods of straw returning.

Mulberroside A attenuates cigarette smoke-induced atherosclerosis in ApoE−/− mice via the Sirt1-HIF-1α axis

ObjectiveThis study investigated whether Mulberryside A (MBA) can attenuate cigarette smoke extract (CSE)-induced autophagy through a Sirt1-dependent pathway, thereby attenuating atherosclerosis in ApoE−/− mice. MethodsAfter treating human umbilical vein endothelial cells (HUVECs) with CSE and MBA, an MTT assay was performed to detect cell activity. Immunofluorescence and Western blotting were used to determine the expressions of autophagy-related proteins, Sirt1 and HIF-1α. Lentivirus and siRNA were used to construct overexpression and silencing (Sirt1 and HIF-1α) models. The in vivo inflammatory effects of CS on atherosclerosis in ApoE−/− mice were assessed by exposing mice to CS and MBA treatment. HE staining was used to detect atherosclerosis in mouse aortic tissue, and electron microscopy was used to detect autophagy of endothelial cells. ResultsCSE promoted autophagy in HUVECs, down-regulated Sirt1, and up-regulated HIF-1α expression. MBA treatment, overexpression of Sirt1, or silencing of HIF-1α attenuated CSE-induced autophagy, while MBA reversed CSE-induced downregulation of Sirt1 and upregulation of HIF-1α. However, overexpression of HIF-1α increased autophagy in HUVECs and attenuated the protective effect of Sirt1 overexpression or MBA on CSE-induced autophagy in HUVECs. In vivo experiments also demonstrated that MBA attenuates CS-induced aortic autophagy in ApoE−/− mice and up-regulates Sirt1 and downregulates HIF-1α expression. ConclusionsMBA attenuates CSE-induced autophagy through the Sirt1-HIF-1α axis, thereby attenuating atherosclerosis in ApoE−/− mice.

Effectiveness of methotrexate and bridging glucocorticoids with or without early introduction of a 6-month course of etanercept in early RA: results of the 2-year, pragmatic, randomised CareRA2020 trial

ObjectivesTo investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction...

Responses of soil fungal and bacterial communities to long-term organic and inorganic nitrogenous fertilizers in an alpine agriculture

Although nitrogen fertilizer is an important measure to increase grain yield, response of soil microbial community to nitrogen fertilizer is still unclear in alpine regions. Based on a long-term (>10 years) nitrogen fertilizer experiment (control, CF: chemical fertilizer, SM: sheep manure; CS: chemical fertilizer + sheep manure) in an alpine agroecosystem of the Lhasa, Xizang, responses of soil bacteria and fungi communities to nitrogen fertilizer was investigated. The CF treatment reduced fungi operational taxonomic unit (OTU) by 13.08 %, phylogenetic diversity by 11.13 % at 10–20 cm, but increased fungi guild number at 0–10 cm by 17.71 %. The SM treatment reduced fungi OTU at 10–20 cm by 11.82 %. Compared to CF and SM treatments, CS treatment had stronger positive effects on bacterial α-diversity, considering that CS treatment but not CF and SM treatments increased bacterial mean nearest taxon distance, species Shannon and Simpson at 10–20 cm. The CF, SM and CS treatments altered fungal community composition at 0–10 and 10–20 cm, bacterial community composition at 10–20 cm, and bacterial species composition at 0–10 cm. The CF and CS treatments altered bacterial phylogenetic composition at 0–10 cm, and the SM and CS treatments altered bacterial functional composition at 0–10 cm. The decreased magnitude of the relative abundance of symbiotroph fungi caused by CS treatment (90.44 %) was stronger than that (65.14 % and 53.62 %) caused by CF and SM treatments at 10–20 cm. Therefore, the SM and CS treatments had stronger effects on soil bacterial functional composition, but the CF treatment had stronger effects on fungal α-diversity. Compared with single application of organic or inorganic nitrogen fertilizer, mixed application of organic and inorganic nitrogen fertilizer was more beneficial to the maintenance and improvement of soil bacterial diversity, but caused more reduction of soil symbiotic fungi and in turn greater potential risk. These scientific findings observed by this study can provide guidance for fertilizer management and soil fertility improvement.

Myoglobin adsorption and saturation kinetics of the cytokine adsorber Cytosorb® in patients with severe rhabdomyolysis: a prospective trial

BackgroundRhabdomyolysis is a serious condition that can lead to acute kidney injury with the need of renal replacement therapy (RRT). The cytokine adsorber Cytosorb® (CS) can be used for extracorporeal myoglobin elimination in patients with rhabdomyolysis. However, data on adsorption capacity and saturation kinetics are still missing.MethodsThe prospective Cyto-SOLVE study (NCT04913298) included 20 intensive care unit patients with severe rhabdomyolysis (plasma myoglobin > 5000 ng/ml), RRT due to acute kidney injury and the use of CS for myoglobin elimination. Myoglobin and creatine kinase (CK) were measured in the patient´s blood and pre- and post-CS at defined time points (ten minutes, one, three, six, and twelve hours after initiation). We calculated Relative Change (RC, %) with: \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$1 - \\left( {concentration(pre - post)\\,/\\,concentration\\left( {pre} \\right)} \\right)*100$$\\end{document}. Myoglobin plasma clearances (ml/min) were calculated with: \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\left( {bloodflow*\\left( {1 - hematocrit} \\right)} \\right)*\\left( {concentration\\left( {pre - post} \\right)\\,/\\,concentration\\left( {pre} \\right)} \\right)$$\\end{document}ResultsThere was a significant decrease of the myoglobin plasma concentration six hours after installation of CS (median (IQR) 56,894 ng/ml (11,544; 102,737 ng/ml) vs. 40,125 ng/ml (7879; 75,638 ng/ml) (p < 0.001). No significant change was observed after twelve hours. Significant extracorporeal adsorption of myoglobin can be seen at all time points (p < 0.05) (ten minutes, one, three, six, and twelve hours after initiation). The median (IQR) RC of myoglobin at the above-mentioned time points was − 79.2% (-85.1; -47.1%), -34.7% (-42.7;-18.4%), -16.1% (-22.1; -9.4%), -8.3% (-7.5; -1.3%), and − 3.9% (-3.9; -1.3%), respectively. The median myoglobin plasma clearance ten minutes after starting CS treatment was 64.0 ml/min (58.6; 73.5 ml/min), decreasing rapidly to 29.1 ml/min (26.5; 36.1 ml/min), 16.1 ml/min (11.9; 22.5 ml/min), 7.9 ml/min (5.5; 12.5 ml/min), and 3.7 ml/min (2.4; 6.4 ml/min) after one, three, six, and twelve hours, respectively.ConclusionThe Cytosorb® adsorber effectively eliminates myoglobin. However, the adsorption capacity decreased rapidly after about three hours, resulting in reduced effectiveness. Early change of the adsorber in patients with severe rhabdomyolysis might increase the efficacy. The clinical benefit should be investigated in further clinical trials.Trial registrationClinicalTrials.gov NCT04913298. Registered 07 May 2021, https//clinicaltrials.gov/study/NCT04913298.Graphical

Risk Perception: Chemical Stimuli in Predator Detection and Feeding Behaviour of the Invasive Round Goby Neogobius melanostomus.

The round goby Neogobius melanostomus is a notoriously invasive fish originating from the Ponto-Caspian region that in recent decades has successfully spread across the globe. One of its primary impacts is direct predation; in addition, when entering new ecosystems, the round goby is likely to become a food resource for many higher native predators. However, little is known either about the indirect effects of predators on the round goby as prey or its feeding behaviour and activity. The non-consumptive effect of the presence of higher native predators presumably plays an important role in mitigating the impact of non-native round gobies as mesopredators on benthic invertebrate communities, especially when both higher- and mesopredators occupy the same habitat. We tested the food consumption probability and gut evacuation rates in round gobies in response to chemical signals from a higher predator, the European eel Anguilla anguilla. Gobies were placed individually in experimental arenas equipped with shelters and exposed to water from a tank in which (a) the higher predator had actively preyed on a heterospecific prey, earthworms Lumbricus sp. (the heterospecific treatment; HS); (b) the higher predator had fed on round gobies (the conspecific treatment; CS); or (c) the water was provided as a control treatment (C). To ensure exposure to the chemical stimuli, this study incorporated the application of skin extracts containing damaged-released alarm cues from the CS treatment; distilled water was used for the remaining treatments. No significant differences were observed in either the food consumption probability or gut evacuation rate in the tested treatments. Despite the lack of reaction to the chemical stimuli, round gobies did exhibit high evacuation rates (R = 0.2323 ± 0.011 h-1; mean ± SE) in which complete gut clearance occurred within 16 h regardless of the applied treatment. This rapid food processing suggests high efficiency and great pressure on resources regardless of the presence or not of a higher predator. These findings hint at the boldness of round gobies, which did not exhibit any pronounced threat sensitivity. This would seem to suggest great efficiency in food processing and a potential competitive advantage over local native species when colonising new ecosystems, irrespective of the presence of native predators. Our study did not detect any non-consumptive effect attributable to the higher predator, given that the feeding activity of the invasive round goby was not altered.

Biochar applications and enzyme activity, carbon dioxide emission, and carbon sequestration in a calcareous soil

Biochar is a carbon-rich product obtained by biomass pyrolysis and is considered as a means of carbon sequestration. However, there is limited knowledge regarding responses of soil respiration and C-cycle enzyme activities to BC in a calcareous soil. In this study, different biochar AS, TS, PP, CS were applied to the soil at different rates (0.5, 1.0, and 1.5%) The highest increase in soil organic C content was observed in the TS treatment, while the AS treatment caused a slight increase of soil organic C. The highest MBC content was recorded in AS treatment and the lowest was observed in TS. The highest CO2-C emission was recorded in the TS treatment. In contrast, the lowest CO2-C emission was observed in the PP treatment due to its high recalcitrant C content and was attributed to a positive priming effect, stabilizing BC mineralization to improve the soil. The highest β-galactosidase enzyme activity was observed in the CS treatment and the lowest activity was observed in AS. The highest change in β-glycosidase enzyme activity was observed of PP treatment and the lowest was in AS biochar application. Thus, TS treatment is recommended to increase the organic C content of soils, and the PP biochar can be used to reduce CO2-C emission. The TS, PP, and CS can be applied to increase enzyme activities. The study clearly shows that the addition of BC to arid soils may have a high potential to improve soil enzyme activities and subsequent carbon sequestration and biochemical cycles.

Soil amendment incorporation increases organic carbon by improving soil agglomerate and soil microbial biomass carbon in the alpine grassland

AbstractSoil amendments aiming to enhance soil quality and bolster carbon sequestration have been extensively investigated. However, the specific impacts of diverse soil amendment types on soil total organic carbon content (TOC), soil aggregate and the growth of ryegrass remain largely unexplored, particularly within the unique context of alpine grassland soils in northwest Sichuan. For this, four soil amendments (CK: no soil amendment, CM: cattle manure 2000 kg ha−1, CS: straw amendment 12,000 kg ha−1 and MS: mushroom substrate 18,000 kg ha−1) were applied to alpine grassland soils over a 2‐year duration, conducted in situ during 2017 and 2018, to investigate the influences of these soil amendments on 0–30 cm soil of TOC, total nitrogen (TN), microbial biomass carbon (MBC), soil aggregation, the above‐ground biomass (DMA) and root traits of ryegrass. Compared to CK, the above‐ground biomass exhibited an average of 348.78% in MS, 287.18% in CS and 115.54% in CM, all reaching statistical significance (p &lt; .05). In the topsoil (0–10 cm), the large soil aggregate rate (LSAR &gt; 0.25 mm) showed a significant increase in CM, CS and MS, particularly in 2018, compared to CK. Our findings further indicated that the improvement in alpine grassland LSAR &gt; 0.25 mm was correlated with a rise in TOC by over 69.89% and MBC by more than 27.14%. The MS treatment resulted in a significant increase in above‐ground biomass and TRL (total root length), while also increasing the levels of TN, MBC and soil aggregates (0.25 ~ 0.5 mm) within the 0–10 cm soil. A similar result of CS treatment was observed to increase the total chlorophyll content and RD (root diameter), as well as an increase in SWC and TOC levels. The TN, MBC, TOC and LSAR contributed 44.77%, 20.87%, 6.46% and 6.45% for ryegrass growth. The SEM indicated that soil amendments promote the growth of ryegrass by improving soil agglomerate and increasing MBC, TOC and TN. Our analysis revealed that ryegrass biomass production was limited by soil nutrients in the alpine grassland of northwest Sichuan. The study also highlights the potential impact of soil amendments on future management practices, contributing to a more comprehensive understanding of the subject.

Radiation resistant chalcopyrite CIGS solar cells: proton damage shielding with Cs treatment and defect healing via heat-light soaking

Cu(In, Ga)Se2 (CIGS) solar cells are recognized as next-generation space technology due to their flexibility, lightweight nature, and excellent environmental stability.

Experience of using mCRL in patients with drug-resistant TB and evaluation of treatment effectiveness and adverse effects

Objective. To study the frequency of adverse events when using new drugs in the treatment regimen for patients with MDR-TB and evaluate the effectiveness of new shorter regimens. Material and methods of research. New shortened regimens have been used for the treatment of patients with MDRTB since September and February 2020 in two institutions (MJ and GS). 225 MDR cases were identified in the treatment regimens, Bdq, Lzd, Lfx, Cfz, Cs were prescribed to 106 patients. Gender balance: men 58 (67.4%), women 28 (32.56%). Almost 67 (79.76%) patients had a bilateral process with decay cavities, and 17 (20.24%) patients had a process without decay. The main side effect of bedaquiline is cardiotoxicity, which manifests itself in prolongation of the QT interval and an increase in QTcF (Fridericia coefficient) calculated using the Fridericia formula. The cardiotoxicity of bedaquiline persists after taking it for another 6 months, i.e. has a cumulative effect. In this connection, with the use of bedaquiline in treatment regimens, an electrocardiographic (ECG) study is initially performed. When monitoring treatment with bedaquiline in the first month, an ECG study is performed after 14 days, before the end of the course of treatment is carried out monthly, after the end of the course for 3 months. SAEs were identified in 3 patients. Hypokalemia, myelosuppression and hyperglycemia were noted accordingly in the 1 patient Peripheral neuropathy (moderate) was observed in 7 patients. Results. Culture conversion was observed in 63 patients (75%) who took Bdq, Lzd, Lfx, Cfz, Cs treatment regimens for 9 months. Time to culture conversion was ≤ mean (or median) in 10 (25%) cases, ≥ mean (or median) in 97 (75%) cases In the remaining 16 (18%) patients, the isolation of mycobacteria persisted, and additional detection of resistance to the main drugs provided a rationale for prolonging the course of treatment. In 5 patients dropped out, these patients were discharged for violations of the nosocomial regimen and took drugs only from 28 days to 2 months. There was no prolongation of the QT interval (0.48-0.51 s). All continued the course with bedaquiline. Peripheral neuropathy (moderate) occurred in 7 (8%) patients taking linezolid. All patients (with mild neuropathy) continued the course with linezolid. These patients were prescribed pyridoxine until the end of the regimen. Myelosuppression was observed in 59 patients. 10 of them had grade 1, 3 had grade 2, and only 1 had grade 3 myelosuppression. Nearly all of those treated with clofozemin had a dark brown skin tone. Treatment outcomes and course completion were 63(75%), failure 16(19%). Conclusion. The effectiveness of shortened treatment regimens for MDR/TB patients with the inclusion of new antiTB drugs (Bdq, Lzd, Lfx, Cfz, Cs) in the treatment regimen turned out to be quite high, side effects were eliminated in time with the help of careful monitoring. In earlier terms, sputum conversion and closure of decay cavities were noted.

ПРОГНОЗИРОВАНИЕ НЕБЛАГОПРИЯТНЫХ КЛИНИЧЕСКИХ ИСХОДОВ ПАЦИЕНТОВ С КАРДИОГЕННЫМ ШОКОМ ПОСЛЕ ОПЕРАЦИЙ НА ОТКРЫТОМ СЕРДЦЕ ПРИ ПОДКЛЮЧЕНИИ ВНУТРИАОРТАЛЬНОЙ БАЛЛОННОЙ КОНТРАПУЛЬСАЦИИ

Aim. To determine preimplantation risk factors and predictors of unfavorable outcome in patients with cardiogenic shock after open-heart surgery, who had an intraoperative system of mechanical circulatory support – intra-aortic balloon contrapulsation. Methods. A retrospective study was conducted at the Republican Scientific and Practical Center “Cardiology” for 2015–2020. It included 66 patients who underwent heart surgery on bypass and who intraoperatively developed cardiogenic shock, refractory to drug therapy, which resulted in the use of intra-aortic balloon counterpulsation. The diagnosis of cardiogenic shock was determined based on the generally accepted criteria, as well as based on the SCAI (Society for Cardiovascular Angiography and Interventions) classification of shock: systolic blood pressure &lt; 90 mmHg for &gt; 30 minutes or the need for infusion of vasopressors or inotropes to achieve the blood pressure of ≥ 90 mm Hg. The Pearson Chi-square test used for nonparametric analysis of qualitative characteristics. The predictors were identified based on logistic regression. Differences were considered significant at p &lt; 0.05 (5%).Results. Risk factors for adverse outcome in case of CS before the use of IABP were: age over 65 years OR = 6.04 [95% CI 1.73 – 21.06], p = 0.003; female gender OR = 3.24 [95% CI 1.064 – 9.873], p = 0.048; vasoactive and inotropic support of more than 42 points OR = 7.85 [95% CI 2.33 – 26.45], p = 0.001; blood lactate of more than 4.7 mmol/l OR = 4.12 [95% CI 1.27 – 13.37], p = 0.014; blood acidity pH &lt; 7.33 OR = 6.34 [95% CI 1.97 – 20.37], p = 0.003; base deficit BE &gt; –5.6 OR = 7.32 [95% CI 2.19 – 24.42], p = 0.001. According to the β-coefficients of the logistic regression equation, predictors were scored as follows: age &gt; 65 years = 2 points, VIP &gt; 42 = 2 points, lactate &gt; 4.7 mmol/L = 1 point. The cumulative probability of 30-day mortality was as follows: 9% when defined as 1 point, 20% – 2 points, 55% – 3 points, 60% – 4 points, 75% – 5 points (Chi-square 24.1; df = 5; p = 0.001). Conclusions. Cardiogenic shock is a fatal complication in cardiac surgery. The use of vasopressor and inotropic drugs has an important role in the treatment of CS; however, escalation of catecholamine doses leads to the progression of multiple organ failure due to hypoperfusion and hypoxia of target organs. Therefore, the use of intra-aortic balloon counterpulsation can improve the results of CS treatment. However, the effect of IABP is limited to increasing cardiac output by no more than 1 l/minute. Based on the calculator we developed, when determining a high risk of an unfavorable outcome of the IABP use, options for circulatory support should be considered including extracorporeal membrane oxygenation, ventricular assist device.

From medical therapy to mechanical support: strategies for device selection and implantation techniques

Abstract Cardiogenic shock (CS) is a complex clinical syndrome with a high risk of mortality. The recent, rapid development of temporary mechanical circulatory support (tMCS) has altered CS treatment. While catecholamines remain the cornerstone of CS therapy, tMCS usage has increased. According to shock severity, different treatment strategies including catecholamines alone, catecholamines and tMCS, or multiple tMCS might be used. State-of-the-art implantation techniques are necessary to avoid complications linked to the invasive nature of tMCS. In particular, bleeding and access-site complications might counteract the potential haemodynamic benefit of a percutaneous ventricular assist device. In this review, we describe the role of catecholamines in CS treatment and present the different tMCS devices with an explanation on how to use them according to CS aetiology and severity. Finally, an overview of the best practice for device implantation is provided.

EARLY-STAGE SELF-ASSEMBLING PEPTIDE HYDROGEL-BASED INTERVENTION FOR ARTICULAR PATELLA CARTILAGE REPAIR

AbstractObjectivesThe aim of this study was to develop an in vitro GAG-depleted patella model and assess the biomechanical effects following treatment with a SAP:CS self-assembling hydrogel.MethodsPorcine patellae (4–6 month old) were harvested and subject to 0.1% (w/v) sodium dodecyl sulfate (SDS) washes to remove GAGs from the cartilage. Patellae were GAG depleted and then treated by injection with SAP (∼ 6 mM) and CS (10 mg) in Ringer's solution through a 30G needle. Native, GAG depleted and SAP:CS treated patellae were tested through static indentation testing, using 15g load, 5mm indenter over 1hr period. The degree of deformation of each group was assessed and compared (Mann-Whitney, p&lt;0.05). Native, GAG depleted, sham (saline only) and SAP:CS treated paired patellae and femurs were additionally characterized tribologically through sequential wear testing when undergoing a walking gait profile (n=6 per group). The cartilage surfaces were assessed and compared (Mann-Whitney, p&lt;0.05) using the ICRS scoring system, surface damage was illustrated through the application of Indian ink.ResultsStatic indentation tests indicated significant increase in indentation deformation of GAG depleted group compared to native group (n=6, p&lt;0.01) and significant reduction in deformation of SAP:CS treated group compared to GAG depleted group (n=6, p&lt;0.05). Sequential wear tests indicated a significant increase in the cartilage damage on the both surfaces of the patellofemoral joint in the GAG depleted group, compared to the native group (n=6, p&lt;0.001), Following SAP:CS treatment, significant protection from damage was observed on femoral surface (n=6, p&lt;0.005), with some non-significant reduction in damage on the patella surface. Sham injections showed no significant increase in damage compared to the native and treated samples.ConclusionsThe ∼50% reduction of GAGs represented a moderate osteoarthritic patella cartilage model. This same loss transferred to the dynamic wear tests with significant changes in the damage on the femoral counter face associated with the GAG loss. SAP:CS treatment showed promise in restoring cartilage stiffness to treat Chondromalacia patella in static indentation tests. Sequential wear tests showed that the SAP:CS treatment protects the cartilage layer of both surfaces in the patellofemoral joint from damage in an extreme degeneration model. The sham injections showed that injecting cartilage with a 30G and saline does not cause any significant damage to the cartilage layer.Declaration of Interest(a) fully declare any financial or other potential conflict of interest

Correlation between Bilirubin Elimination with the Cytokine Adsorber CytoSorb® and Mortality in Critically Ill Patients with Hyperbilirubinemia

Introduction: Hyperbilirubinemia is often the first evidence for any kind of liver disorder and over one-third of all patients in intensive care units (ICU) show elevated bilirubin concentrations. In critically ill patients, high concentrations of serum bilirubin are correlated with a poor outcome. Therapies to lower bilirubin concentrations are often just symptomatically and their effect on the patients’ outcome is hardly evaluated. Therefore, this study investigates whether the extracorporeal elimination of bilirubin with the cytokine adsorber CytoSorb^® (CS) reduces mortality in patients with hyperbilirubinemia. Methods: Patients with bilirubin concentrations >10 mg/dL at the ICU were screened for evaluation from 2018 to 2020. Patients with kidney replacement therapy and older than 18 years were included. Patients with continuously decreasing bilirubin concentrations after liver transplantation or other liver support systems (i.e., Molecular Adsorbents Recirculating System [MARS^®], Advanced Organ Support [ADVOS]) were excluded. CS therapy was used in clinical routine and was indicated by the treating physicians. Statistical analysis was performed with IBM SPSS statistics utilizing a multivariate model. Primary outcome measure was the effect of CS on the 30-day mortality. Results: Data from 82 patients (mean Simplified Acute Physiology Score [SAPS] II: 74 points, mean bilirubin: 18 mg/dL, mean lactate: 3.7 mmol/L) were analyzed. There were no significant differences in patients with and without CS treatment. The multivariate model showed no significant effect of CS therapy (p = 0.402) on the 30-day mortality. In addition, a significant effect of bilirubin concentration (p = 0.274) or Model for End-Stage Liver Disease score (p = 0.928) on the 30-day mortality could not be shown. In contrast, lactate concentration (p = 0.001, b = 0.044) and SAPS II (p = 0.025, b = 0.008) had significant impact on 30-day mortality. Conclusion: The use of CS in patients with hyperbilirubinemia did not result in a significant reduction in 30-day mortality. Randomized and controlled studies with mortality as primary outcome measure are needed in the future to justify their use.

Partial replacement of chemical fertilizers with animal manures in an apple orchard: Effects on crop performance and soil fertility

The combined use of chemical fertilisers with organic materials in crop fertilization is an essential approach to transition towards a more sustainable and resilient agriculture in Europe. In an apple orchard, chemical fertilisers (CF) were partially (25 to 57%) replaced with animal manure (cattle slurry - CS, acidified cattle slurry - ACS, cattle solid manure - CsM, and poultry manure - PM), based on the crop's nitrogen (N) requirements. Apple production and soil properties were monitored during a 3-year experiment. At the end of the third year, leaf N was higher in the control treatment (CTRL, 100% CF). Apple production was, on average, higher in the CS treatment, although not significantly different from the CTRL. Fruit analysis showed that replacing CF with animal manures did not significantly impacted fruit quality (weight, ºBrix and firmness). Soil organic carbon (SOC), N and exchangeable potassium (K+) were significantly higher in the manure treatments. The increase in soil K+ in the manure treatments consequently increased soil K/magnesium (Mg) ratio, slightly mitigating K and Mg antagonism, as seen by the increase in fruit K. However, K content was still deficient in fruits and leaves in all treatments. It can be concluded that the partial replacement of chemical fertilisers by animal manures (CS, ACS and PM) had a positive effect on soil health with no decrease of apple production.

Effect of yeast supplementation on growth parameters and metabolomics of black soldier fly larvae,Hermetia illucens (L.) (Diptera: Stratiomyidae)

Enhancement of black soldier fly (BSF) larval body weight with nutraceutical metabolites is a crucial step in utilising BSF larvae as food and feed. As BSF larvae are found in natural habitats comprising decaying organic matter and thriving with yeast species, we hypothesis that metabolic interactions between BSF larvae and the yeast present in their gut will have the greatest influence on the nutritional composition and life cycle of the BSF larvae. In the present study, we compared BSF larvae that were fed withSaccharomyces cerevisiae (Sc), a yeast species used for rearing BSF andCandida spp. (Cs), yeast-like fungi that are common in the BSF larval gut environment. The effect of the yeasts on 5th instar larval body weight was tested, and alteration of metabolic regulation and its impact on related pathways was analysed using liquid chromatography-mass spectrometry (LC-MS) and MetaboAnalyst 5.0 version. The Cs feeding treatment significantly increased larval body weight compared to the Sc treatment. The metabolic pathway analysis demonstrated that the significantly over-accumulated metabolites in the Cs treatment (compared to the Sc treatment) were tyrosine, purine, histidine and vitamin B6 metabolism, while the significantly down-accumulated metabolites in Cs (compared to the Sc treatment) were arginine biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, and valine, leucine and isoleucine biosynthesis. In addition, metabolites related to phenylalanine metabolism, D-glutamine and D-glutamate metabolism, and alanine, aspartate, and glutamate metabolism were down-accumulated. However, further study is required on both the BSF and yeast gene expression related to these metabolic pathways in order to better understand yeast-insect metabolite interactions. The overall conclusion of this study is that a supply of yeasts that are adapted to the BSF digestive system contributes to altered metabolic pathways in the BSF larvae and enhances larval body weight, as well as improving nutrient status.

Intrathecal administration of conditioned serum from different species resolves Chemotherapy-Induced neuropathic pain in mice via secretory exosomes

Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of chemotherapy for cancer, and has limited effective treatment options. Autologous conditioned serum (ACS) is an effective biologic therapy used by intra-articular injection for patients with osteoarthritis. However, ACS has not been systematically tested in the treatment of peripheral neuropathies such as CIPN. It has been generally assumed that the analgesic effect of this biologic therapy results from augmented concentrations of anti-inflammatory cytokines and growth factors. Here we report that a single intrathecal injection of human conditioned serum (hCS) produced long-lasting inhibition of paclitaxel chemotherapy-induced neuropathic pain (mechanical allodynia) in mice, without causing motor impairment. Strikingly, the analgesic effect of hCS in our experiments was maintained even 8 weeks after the treatment, compared with non-conditioned human serum (hNCS). Furthermore, the hCS transfer-induced pain relief in mice was fully recapitulated by rat or mouse CS transfer to mice of both sexes, indicating cross-species and cross-sex effectiveness. Mechanistically, CS treatment blocked the chemotherapy-induced glial reaction in the spinal cord and improved nerve conduction. Compared to NCS, CS contained significantly higher concentrations of anti-inflammatory and pro-resolving mediators, including IL-1Ra, TIMP-1, TGF-β1, and resolvins D1/D2. Intrathecal injection of anti-TGF-β1 and anti-Il-1Ra antibody transiently reversed the analgesic action of CS. Nanoparticle tracking analysis revealed that rat conditioned serum contained a significantly greater number of exosomes than NCS. Importantly, the removal of exosomes by high-speed centrifugation largely diminished the CS-produced pain relief, suggesting a critical involvement of small vesicles (exosomes) in the beneficial effects of CS. Together, our findings demonstrate that intrathecal CS produces a remarkable resolution of neuropathic pain mediated through a combination of small vesicles/exosomes and neuroimmune/neuroglial modulation.

86 Biomarkers of Inflammation in Neonatal Calves Supplemented with Condensed Solubles from Milk Permeate

Abstract Neonatal and weaning periods are the most challenging phases for enteric infections in dairy calves. While different approaches are used to minimize calf health issues, the neonatal diet remains the core approach to enhance pre- and post-weaning animal health and performance. Previous studies have shown that bioactive compounds, including oligosaccharides present in the diet of neonatal dairy calves, enhanced their growth performance post-weaning. However, the effects of oligosaccharides supplementation during the neonatal period and the impact on the health status of the calf remain to be elucidated. Thus, we aimed to evaluate blood biomarkers of inflammation in calves supplemented with condensed solubles from milk permeate (CS) during the neonatal period (from birth to 21 d) of dairy calves. Twenty-four newborn Holstein calves (n = 12/group) housed in individual hutches were used in a randomized complete block design study. Calves were blocked by birth date and sex. At 2-days old, calves were randomly assigned into two groups (n = 6 females and 6 males per group): control with no supplement; or treatment with 50 g/d of CS. Both treatment and control groups were fed pasteurized waste milk during the preweaning period. Calves were fed 2.83 L of pasteurized waste milk 2×/d during week 1 to 5, 1×/d in week 6, and weaned at week 7. At each milk feeding during week 1 to 5, 25 g of CS was added to the pasteurized waste milk for each calf on the CS treatment. Healthy scores were recorded daily. Calf growth measurements and blood samples were collected weekly. Data were analyzed using MIXED procedures of SAS 9.4 with repeated measures. Significant differences were declared at P &amp;lt; 0.05. Overall, body weight, fecal and respiratory scores were similar between groups during the preweaning period. During the first 3 weeks of age, a group×sex×time interaction was observed for the enzyme myeloperoxidase (MPO) expressed by neutrophils. Female calves on the CS treatment had decreased MPO concentrations in the blood relative to the female controls at week 3. Other biomarkers of inflammation (i.e., haptoglobin) or consequent liver response (i.e., albumin, paraoxonase) did not differ between groups. Based on these parameters, there was no evidence of systemic inflammation during the first 21 days of age. However, circulating MPO is an indicative of phagocytosis by neutrophils resulting in a local or systemic inflammatory responses. The decreased MPO in CS female calves can be associated with a lesser microbial infiltration in the gut. The latter suggests that oligosaccharides from the diet stimulate the growth of commensal microbiota on the host, which serve as decoy receptors to pathogenic microorganisms (i.e., blocking microbial infiltration). Overall, these findings suggest that bioactive molecules as feed supplements such as CS can help the local immune response in neonatal dairy calves.