The Effect of Chitosan Hydrolysate on Solanum Lycopersicum Plant Growth

Chitosan is a well-known subjectof researchbecause of its beneficial properties, including its antibacterial and fungicidal activity, as well as its effect on plant physiology. One of the maindifficulties in agricultural chitosan implementation is the poor solubility of high molecular chitosan in water. Reducing themolecular weight of chitosan by acid hydrolysis increases its solubility. This research studied the effect of chitosan hydrolysate on the germination and development ofSolanum lycopersicum L. plants. Theeffects of chitosan hydrolysate on seed germination, shoot development in the first week of development and in the first month of development were evaluated. According to the results, high concentrations of chitosan hydrolysate completely inhibited seed germination. However, short-term treatment by high concentrations of chitosan hydrolysate stimulatedthe development of seedlings, leading to substantially longerroots. Regular root application of high concentrations of chitosan hydrolysate inhibited plant development. Keywords: chitosan hydrolysate, chitosan, plant growth regulators, plant germination

Short-Term Treatment with Alirocumab, Flow-Dependent Dilatation of the Brachial Artery and Use of Magnetic Resonance Diffusion Tensor Imaging to Evaluate Vascular Structure: An Exploratory Pilot Study

Background: Short-term effects of alirocumab on vascular function have hardly been investigated. Moreover, there is a scarce of reliable non-invasive methods to evaluate atherosclerotic changes of the vasculature. The ALIROCKS trial was performed to address these issues using standard ultrasound-based procedures and a completely novel magnetic resonance-based imaging technique. Methods: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were 2 visits to the study site, the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. The key outcome measures included the change of carotid vessel wall fractional anisotropy, a novel magnetic resonance-based measure of vascular integrity, and the changes of carotid intima-media thickness and flow-dependent dilatation of the brachial artery measured with ultrasound. Results: A total of 19 patients completed the trial, 2 patients stopped treatment, 3 patients did not undergo the second visit due to the COVID pandemic. All of them had atherosclerotic vascular disease. Their mean (standard deviation) LDL-cholesterol concentration was 154 (85) mg/dL at baseline and was reduced by 76 (44) mg/dL in response to alirocumab treatment (p < 0.001, n = 19). P-selectin and vascular endothelial growth factors remained unchanged. Flow-dependent dilatation of the brachial artery (+41%, p = 0.241, n = 18), carotid intima-media thickness (p = 0.914, n = 18), and fractional anisotropy of the carotid artery (p = 0.358, n = 13) also did not significantly change. Conclusion: Despite a nominal amelioration for flow-dependent dilatation, significant effects of short-term treatment with alirocumab on vascular function were not detectable. More work would be needed to evaluate, whether fractional anisotropy may be useful in clinical atherosclerosis research.

Idiopathic Intracranial Hypertension: Current Neuroophthalmologic Points

Idiopathic intracranial hypertension (ICH) is a neuroophophthalmologic syndrome, the main ophthalmologic symptoms of which are vision loss and bilateral swelling of optic nerve disks (OD). The article provides a review covering various aspects of ICH. Epidemiology: ICH occurs mainly in women aged 20–45 years with body overweight. In this group of patients world incidence is 12–20 per 100 000 of population per year. In the total population it represents 0.5–2 cases per 100 000 of population per year. The eightfold gender predominance of women with ICH is observed. Etiology is not fully known until present time. The reliable connection between obesity in childbearing age women and menstrual cycle disorders as evidences of hormonal changes has been established. The probable mechanisms of increase of ICP are supposed: hyperproduction of and disturbances of its absorption, CSF mechanical pressure on the optic nerve sheath; restriction of venous outflow from the brain due to the pathology of venous sinuses; stimulating effect of abundant vitamin A in diet resulting in the fat tissue formation with the development of obesity; expression of the protein aquaporin, involved in the regulation of body mass and water metabolism in the subarachnoid space. Clinical manifestations. Ophthalmologic symptoms of ICH: transient visual impairment, sustained loss of visual acuity, photopsy, retrobulbar pain, diplopia. Non-ophthalmologic symptoms: headache, throbbing tinnitus, hearing loss, dizziness. Diagnostics. The valuable diagnostic data can be obtained by visual field investigation, ophthalmoscopic examination with revealing of bilateral OD-edema, OD and retinal optical coherent tomography, orbital ultrasound examination, brain MRI with venography. Treatment. Non-drug therapy: weight loss, lowcalorie diet with limited water and salt intake. Drug therapy: long-term oral use of carbonic anhydrase inhibitors (acetazolamide, topiramate). High doses of steroids (methylprednisone) are used for short-term treatment of patients with fulminant disease type before surgery. Surgery: bypass surgery, cerebral venous sinus stenting and fenestrations of the optic nerve sheath: bariatric surgery with reducing of stomach volume.

Effects of in vitro short- and long-term treatment with telomerase inhibitor in U-251 glioma cells

BACKGROUND: The inhibition of the enzyme telomerase (TERT) has been widely investigated as a new pharmacological approach for cancer treatment, but its real potential and the biochemical consequences are not totally understood. OBJECTIVE: Here, we investigated the effects of the telomerase inhibitor MST-312 on a human glioma cell line after both short- and long-term (290 days) treatments. METHODS: Effects on cell growth, viability, cell cycle, morphology, cell death and genes expression were assessed. RESULTS: We found that short-term treatment promoted cell cycle arrest followed by apoptosis. Importantly, cells with telomerase knock-down revealed that the toxic effects of MST-312 are partially TERT dependent. In contrast, although the long-term treatment decreased cell proliferation at first, it also caused adaptations potentially related to treatment resistance and tumor aggressiveness after long time of exposition. CONCLUSIONS: Despite the short-term effects of telomerase inhibition not being due to telomere erosion, they are at least partially related to the enzyme inhibition, which may represent an important strategy to pave the way for tumor growth control, especially through modulation of the non-canonical functions of telomerase. On the other hand, long-term exposure to the inhibitor had the potential to induce cell adaptations with possible negative clinical implications.

Improving Tuberculosis Treatment Adherence Support: The Case for Targeted Behavioral Interventions

Problem definition: Lack of patient adherence to treatment protocols is a main barrier to reducing the global disease burden of tuberculosis (TB). We study the operational design of a treatment adherence support (TAS) platform that requires patients to verify their treatment adherence on a daily basis. Academic/practical relevance: Experimental results on the effectiveness of TAS programs have been mixed; and rigorous research is needed on how to structure these motivational programs, particularly in resource-limited settings. Our analysis establishes that patient engagement can be increased by personal sponsor outreach and that patient behavior data can be used to identify at-risk patients for targeted outreach. Methodology: We partner with a TB TAS provider and use data from a completed randomized controlled trial. We use administrative variation in the timing of peer sponsor outreach to evaluate the impact of personal messages on subsequent patient verification behavior. We then develop a rolling-horizon machine learning (ML) framework to generate dynamic risk predictions for patients enrolled on the platform. Results: We find that, on average, sponsor outreach to patients increases the odds ratio of next-day treatment adherence verification by 35%. Furthermore, patients’ prior verification behavior can be used to accurately predict short-term (treatment adherence verification) and long-term (successful treatment completion) outcomes. These results allow the provider to target and implement behavioral interventions to at-risk patients. Managerial implications: Our results indicate that, compared with a benchmark policy, the TAS platform could reach the same number of at-risk patients with 6%–40% less capacity, or reach 2%–20% more at-risk patients with the same capacity, by using various ML-based prioritization policies that leverage patient engagement data. Personal sponsor outreach to all patients is likely to be very costly, so targeted TAS may substantially improve the cost-effectiveness of TAS programs.

Protective Effects of Aminooxyacetic Acid on Colitis Induced in Mice with Dextran Sulfate Sodium

As a known inhibitor of pyridoxal phosphate-dependent transaminase glutamic-oxaloacetic transaminase 1 (GOT1), aminooxyacetic acid (AOAA) has been pointed out to have potential pharmacological effects in antiepileptic, anticonvulsant, antibacterial, cancer cell proliferation inhibition, and acute myocardial infarction (MI) relief. However, its role in inflammatory bowel disease (IBD) has not been reported. Through the in vivo experiment of dextran sulfate sodium- (DSS-) induced colitis in mice, it was found that AOAA significantly attenuated the symptoms, signs, and pathological changes of colitis. In addition, AOAA treatment prevented gut barrier damages by enhancing the expression of zona occludens- (ZO-) 1, occludin, claudin-1, and E-cadherin and recovering the upregulation of the most abundant intermediate filament protein (vimentin). Moreover, the release of interleukin- (IL-) 1β, IL-6, and tumour necrosis factor- (TNF-) α was suppressed, yet the level of IL-10 was upregulated by AOAA treatment compared to the model group. Furthermore, it was shown that AOAA administration boosted M2-like phenotype and effectively reduced M1 macrophage phenotype in the lamina propria of mouse colonic epithelium. Similarly, the effect of AOAA was verified in vitro. AOAA effectively inhibited the classically activated M1 macrophage phenotype and proinflammatory cytokine (IL-1β, TNF-α, and IL-6) expression induced by lipopolysaccharide (LPS) and promoted M2-like phenotype. Collectively, this study reveals for the first time that short-term treatment of AOAA can significantly alleviate DSS-induced acute colitis by regulating intestinal barrier function and macrophage polarization, which provides a theoretical basis for the potential use of AOAA in the treatment of IBD.

Multicomponent Solid Fuel Production Technology Using Waste Water

An assessment is given to the problems of urban wastewater sludge utilization in our country and abroad, with determination of formation and usage level. Global trends in the reduction of carbon dioxide emissions exacerbate the urgency of solving the designated tasks. At the same time, recently, in connection with the EU’s plans to introduce a cross-border carbon levy, it has become necessary to reduce the carbon footprint from burning traditional fuels, which is an urgent problem of modern society. One of the directions that provide a solution to this problem is the replacement of part of the hydrocarbon fuel by the consumption of multicomponent solid fuel based on the use of combustible waste that is part of the multicomponent fuel. This solid fuel can be used to meet the needs of small consumers, for example, in the autumn-summer period to generate a drying agent for the preparation of grain on the threshing-floor, in small boiler houses, in sand drying plants of locomotive depots, heat installations of hangars and workshops, as well as in other heat-generating installations operating on solid fuels. At the same time, solving the problem of reducing the carbon footprint for Belarus is closely related to another urgent task – reducing the energy component of industrial products and the environmental consequences of storing accumulated and generated waste. The paper presents the results of joint scientific research in the field of application of modern technologies and equipment using electrohydraulic treatment to reduce and minimize the level of anthropogenic and polluting substances in wastewater sludge. The described technological equipment, technology and post-treatment modes reduce the content of harmful substances in the wastewater sludge composition even with short-term treatment. An assessment of the effectiveness of the developed technology for the use of sewage sludge is given, using the method of wet multicomponent briquetting to obtain a multicomponent fuel. The presented process flow diagram of multicomponent briquetting using sewage sludge and plant-wood waste directly shows the undeniable advantages of using watered wastewater sludge as a raw material for the production of solid fuel. At the same time, the optimally selected ratio of components and moisture content of the briquetted composition solves a number of technologically difficult problems that cannot be realized using traditional briquetting technologies. The presented data of the conducted research and the developed technology make it possible to expand the area of using wastewater sludge as a secondary renewable material resource.

765 Is acute response to calcium sensitizers drugs predictive of response to cardiac contractility modulation in NYHA IV patients?

A 53-years old man presented to our institution with a diagnosis of decompensated heart failure NYHA Class IV. He had a history of ischaemic heart disease with severe biventricular dysfunction, diabetes, hypertension, dyslipidaemia, advanced chronic kidney disease, previous explanation of dual-chamber implantable electronic device (ICD) due to endocarditis and subsequent implantation of subcutaneous ICD in primary prevention. Home therapy included uptitrated angiotensin-converting enzyme inhibitor, β-blocker, loop-diuretic, spironolactone, acetylsalicylic acid, and oral hypoglycemics. Clinical examination showed signs and symptoms of systemic and pulmonary congestion with pleural effusion and ascites. Echocardiography revealed diffuse left ventricular (LV) hypokinesis with an ejection fraction (EF) of 25%, severe right ventricular dysfunction and increased filling pressures. He was treated with high dose of i.v. diuretics with mild improvement of dyspnoea. However, haemodynamic stability was labile with worsening of symptoms as soon as mild down-titration of iv diuretics was attempted. Levosimendan, a calcium-sensitizer inodilator, indicated for short-term treatment of acutely decompensated severe chronic heart failure (HF), was administered with good clinical response. Thus, we thought that the patient could have benefited from contractility modulation therapy (CCM) which acts on intramyocardial calcium handling. CCM is a novel therapeutic option for patients with classes III–IV HF with EF ≥ 25% to ≤ 45% and narrow QRS complex that acts on intramyocardial calcium-handling. CCM proved effective in alleviating symptoms, improving exercise tolerance and quality of life, and reducing hospitalization rates in HF. It improves myocardial contractility, reverses the foetal myocyte gene program associated with HF and facilitates cardiac reverse remodelling. Therefore, an Optimizer Smart System (Impulse Dynamics) was implanted. Two pacing electrodes were placed on the interventricular septum in apical and mid-septal position, respectively. The leads were connected to a pulse-generator in a right pectoral pocket. In the following days, we observed a progressive improvement in clinical status, with gradual resolution of peripheral oedema, dyspnoea and fatigue and significant weight loss. Six-month echocardiography showed a stable value of EF and significant improvement in stroke volume (35.2 ml from 24.8 ml at baseline). The patient did not undergo further hospitalization for decompensated HF and was in stable ambulatory NYHA Class IV. We believe CCM is an option in patients with advanced HF in which avoiding recurrent hospitalizations, with their overt increase mortality, is often a challenging therapeutic goal. 765 Figure

Impact of Graft-Resident Leucocytes on Treg Mediated Skin Graft Survival

The importance and exact role of graft-resident leucocytes (also referred to as passenger leucocytes) in transplantation is controversial as these cells have been reported to either initiate or retard graft rejection. T cell activation to allografts is mediated via recognition of intact or processed donor MHC molecules on antigen-presenting cells (APC) as well as through interaction with donor-derived extracellular vesicles. Reduction of graft-resident leucocytes before transplantation is a well-known approach for prolonging organ survival without interfering with the recipient’s immune system. As previously shown by our group, injecting mice with IL-2/anti-IL-2 complexes (IL-2cplx) to augment expansion of CD4 T regulatory cells (Tregs) induces tolerance towards islet allografts, and also to skin allografts when IL-2cplx treatment is supplemented with rapamycin and a short-term treatment of anti-IL-6. In this study, we investigated the mechanisms by which graft-resident leucocytes impact graft survival by studying the combined effects of IL-2cplx-mediated Treg expansion and passenger leucocyte depletion. For the latter, effective depletion of APC and T cells within the graft was induced by prior total body irradiation (TBI) of the graft donor. Surprisingly, substantial depletion of donor-derived leucocytes by TBI did not prolong graft survival in naïve mice, although it did result in augmented recipient leucocyte graft infiltration, presumably through irradiation-induced nonspecific inflammation. Notably, treatment with the IL-2cplx protocol prevented early inflammation of irradiated grafts, which correlated with an influx of Tregs into the grafts. This finding suggested there might be a synergistic effect of Treg expansion and graft-resident leucocyte depletion. In support of this idea, significant prolongation of skin graft survival was achieved if we combined graft-resident leucocyte depletion with the IL-2cplx protocol; this finding correlated along with a progressive shift in the composition of T cells subsets in the grafts towards a more tolerogenic environment. Donor-specific humoral responses remained unchanged, indicating minor importance of graft-resident leucocytes in anti-donor antibody development. These results demonstrate the importance of donor-derived leucocytes as well as Tregs in allograft survival, which might give rise to new clinical approaches.

Long-term, Real-life, Observational Study in Treating Outpatient Ulcerative Colitis with Golimumab

Background and Aims: Several studies have found Golimumab (GOL) effective and safe in the short-term treatment of ulcerative colitis (UC), but few long-term data are currently available from real world. Our aim was to assess the long-term real-life efficacy and safety of GOL in managing UC outpatients in Italy. Methods: A retrospective multicenter study assessing consecutive UC outpatients treated with GOL for at least 3-month of follow-up was made. Primary endpoints were the induction and maintenance of remission in UC, defined as Mayo score ≤2. Several secondary endpoints, including clinical response, colectomy rate, steroid free remission and mucosal healing, were also assessed during the follow-up. Results: One hundred and seventy-eight patients were enrolled and followed up for a median (IQR) time of 9 (3-18) months (mean time follow-up: 33.1±13 months). Clinical remission was achieved in 57 (32.1%) patients: these patients continued with GOL, but only 6 patients (3.4%) were still under clinical remission with GOL at the 42nd month of follow-up. Clinical response occurred in 64 (36.4%) patients; colectomy was performed in 8 (7.8%) patients, all of them having primary failure. Steroid-free remission occurred in 23 (12.9%) patients, and mucosal healing was achieved in 29/89 (32.6%) patients. Adverse events occurred in 14 (7.9%) patients. Conclusions: Golimumab does not seem able to maintain long-term remission in UC in real life. The safety profile was good.