N-Reacetylated Oligochitosan: pH Dependence of Self-Assembly Properties and Antibacterial Activity

© 2017 American Chemical Society.Oligochitosan (short chain chitosan) is more soluble in acidic aqueous media than a high molecular weight (MW) chitosan, but its antimicrobial activity decreases with increase in degree of acetylation (DA) and increase in pH above a critical pH threshold point. In the present study, oligochitosans varying in MW were additionally N-acetylated and their self-assembly properties and antibacterial activity toward Staphylococcus aureus and Escherichia coli were investigated in a wide pH range as a function of MW and DA. Light scattering studies reveals that reacetyleted oligochitosan with Mw ≤ 11 kDa is completely soluble in alkaline media (up to pH 12.5), if its DA is not less than 16%. Reacetylated chitosans with DA ∼ 30% are solubile in the entire pH range up to 12.5, if their Mw is not higher than 25 kDa, but they aggregate and precipitate from the solution at pH ≥ 8 when their Mw is above 25 kDa. Considering the influence of DA and MW, the antibacterial activity of reacetylated oligochitosans is maximal in the short interval of DA 16-28% at pH 7.4. These results are promising for expanding practical application of oligochitosan in pharmaceutical, cosmetic, and food compositions

Application of PCR-based approaches for evaluation of cell-free DNA fragmentation in colorectal cancer

Cell-free DNA (cfDNA) testing is the core of most liquid biopsy assays. In particular, cfDNA fragmentation features could facilitate non-invasive cancer detection due to their interconnection with tumor-specific epigenetic alterations. However, the final cfDNA fragmentation profile in a purified sample is the result of a complex interplay between informative biological and artificial technical factors. In this work, we use ddPCR to study cfDNA lengths in colorectal cancer patients and observe shorter and more variable cfDNA fragments in accessible chromatin loci compared to the densely packed pericentromeric region. We also report a convenient qPCR system suitable for screening cfDNA samples for artificial high molecular weight DNA contamination

Antifungal activity of oligochitosans (short chain chitosans) against some Candida species and clinical isolates of Candida albicans: Molecular weight-activity relationship

A series of oligochitosans (short chain chitosans) prepared by acidic hydrolysis of chitosan and characterized by their molecular weight, polydispersity and degree of deacetylation were used to determine their anticandidal activities. This study has demonstrated that oligochitosans show a high fungistatic activity (MIC 8-512 μg/ml) against Candida species and clinical isolates of Candida albicans, which are resistant to a series of classic antibiotics. Flow cytometry analysis showed that oligochitosan possessed a high fungicidal activity as well. For the first time it was shown that even sub-MIC oligochitosan concentration suppressed the formation of C. albicans hyphal structures, cause severe cell wall alterations, and altered internal cell structure. These results indicate that oligochitosan should be considered as a possible alternative/additive to known anti-yeast agents in pharmaceutical compositions. © 2014 Elsevier Masson SAS. All rights reserved

Effect of Molecular Weight and Degree of Acetylation on Adjuvantive Properties of Chitosan Derivatives

© 2018, Pleiades Publishing, Inc. The hemostatic and immunostimulating activity and cytotoxicity were determined for a number of chitosans differing in molecular weight (from 3 to 510 kDa) and degree of acetylation (from 1 to 25 mol%) that were used as adjuvants in inactivated poliomyelitic, influenza, and live influenza vaccines. It has been shown that the hemostatic activity of chitosan increased sharply with an increase in its molecular weight. In oligochitosan with a molecular weight of <16 kDa, it was smaller by a factor of 15–100 than in chitosan with a molecular weight of 20–510 kDa. The level of increase in the immunogenicity of vaccines containing oligochitosan as adjuvants was not lower than that for the vaccine including high-molecular chitosan. However, the immunostimulatory activity of oligochitosan depended on the degree of acetylation, reaching a maximum value at 6 mol%. It was shown that all oligochitosans and chitosans with a molecular mass below ~50 kDa showed almost no cytotoxicity at a concentration of ≤2.5 mg/mL, which enable their use as adjuvants for inactivated and live vaccines at the optimal ratio of molecular weight to the degree of acetylation

Molecular weight and pH aspects of the efficacy of oligochitosan against methicillin-resistant Staphylococcus aureus (MRSA)

Oligochitosan samples varying in molecular weight (Mw) and having narrow polydispersities were prepared by means of depolymerization of chitosan in hydrochloric acid, and their antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) was measured at pH values 5.5-8.0. The antibacterial testing of oligochitosans obtained showed that oligochitosans having Mw in the range of 0.73-20.0 kDa could be used both at slightly acidic and neutral pH values, and that the activity against MRSA remained moderate for oligochitosan samples having Mw about 3-5 kDa even at slightly basic pH values. The self-assembling behavior of oligochitosan macromolecules in the dilute solution at various pH values as a function of chain length was investigated. At first it was shown that oligochitosans formed supramolecular aggregates in dilute solutions below the critical pH value 6.5. Despite the aggregation phenomenon, the formation of nano-sized aggregates did not prevent oligochitosan from demonstrating the bactiostatic activity. © 2011 Elsevier Ltd. All Rights Reserved

APLIKASI MANAJEMEN KEGIATAN UNTUK ORGANISASI NON PROFIT BERBASIS WEBSITE

Suatu organisasi memiliki berbagai program kerja, yang di dalamnya ada kepanitian khusus. Biasanya manajemen kegiatan yang berisi pengelolaan keuangan pada masing-masing organisasi dan lembaga dikepalai oleh bendahara. Pengelolaan keuangan tersebut menjadi sebuah kebutuhan, karena bendahara tersebut wajib selalu melaporkan pencatatan keuangan. Tentu akan menjadi tidak efektif jika melakukan pencatatan keuangan harus melakukannya secara manual. Di samping susah, pencatatan secara manual sangat beresiko seperti rusak dan hilangnya buku pencatatan. Ada lagi pencatatan dengan cara lain yaitu menggunakan software yang sudah ada seperti Microsoft Excel, namun hal tersebut masih kurang efisien dan kurang efektif sehingga diperlukan tools pencatatan yang lebih baik agar mencapai tujuan dan sasaran yang diinginkan. Subjek penelitian yang dibahas pada penelitian ini adalah aplikasi pengelolaan keuangan untuk organisasi non profit berbasis website. Langkah pengembangan aplikasi yaitu menggunakan waterfall model. Dari penelitian yang dilakukan menghasilkan sebuah website tentang ”aplikasi manajemen kegiatan untuk organisasi non profit berbasis website” yang dapat digunakan untuk melakukan manajemen kegiatan bagi organisasi non profit sehingga pekerjaan seorang bendahara menjadi mudah dan efektif.Keywords: Manajemen Kegiatan, Nonprofit Online, Organisasi Non Profit

Comparison of the results of ⁸⁵Kr transport modeling with the ACURATE field experiment data

© 2017, Allerton Press, Inc.Currently the Nuclear Safety Institute of the Russian Academy of Sciences (NSI RAS) jointly with the Hydrometcenter of Russia is developing the system for forecasting the transfer of radio-active substances in the atmosphere in case of radiation accidents at Russian nuclear power plants. The operation of the system is based on the numerical hydrodynamic model which allows forecasting meteorological parameters and is coupled with the mesoscale dispersion model of the transfer ofradioactive substances in the atmosphere. The results are presented of 85Kr transport modeling under the conditions of the ACURATE experiment with three transport models: FLEXPART, HYSPLIT, and the model from the NOSTRADAMUS software package. It is demonstrated that all three Lagrangian models can give a qualitative description of concentration fields from the ACURATE experiment with the best value of the RANK metric (2.5) based on three statistics

LIS-3 Acute Coronary Syndrome Registry: Changes in Clinical and Demographic Characteristics and Tactics of Prehospital and Hospital Treatment of Surviving Patients After Acute Coronary Syndrome Over a 4-Year Period

Aim. To study the changes in clinical and demographic characteristics, risk factors, treatment tactics, the dynamics of drug therapy at the prehospital stage and prescribed during discharge from the cardiology department over a 4-year period in patients after acute coronary syndrome (ACS) with ST segment elevation and ACS without ST segment elevation. Material and methods. Data from the LIS-3 prospective registry (Lyubertsy mortality study) was used. Patients admitted to the cardiology department of the Lyubertsy district hospital No. 2 for the first 9 months of 2014 (n=104) and for the first 9 months of 2018 (n=223) with a diagnosis of “ACS with ST segment elevation and ACS without ST segment elevation” and with a confirmed diagnosis at discharge “acute myocardial infarction” (AMI) or “unstable angina” (NSA) were included into the study. Comparison of clinical and demographic indicators, risk factors, the frequency of use of acetylsalicylic acid, clopidogrel, statins, beta-blockers, ACE inhibitors, angiotensin II receptor antagonists, anticoagulants at the prehospital stage and during discharge from the hospital were performed. Results. Significant differences in the gender and age composition of patients were not found. The number of working patients increased. Compared to 2014, in 2018 the number of patients with arterial hypertension increased (64.4% and 75.8%, respectively, p=0.047), and with coronary heart disease decreased significantly (39.4% and 22.4%, respectively, p=0.004), however, the incidence of atrial fibrillation, history of AMI, and cerebral stroke did not change over the period under consideration. The frequency of concomitant diseases did not practically change, except for kidney diseases, which have become more common. A significant decrease in the frequency of thrombolysis and a significant (more than 6-fold) increase in angioplasty with stenting were found. Patients before ACS in 2014 received less antiplatelet agents than in 2018, including dual antiplatelet therapy, ACE inhibitors were prescribed more often. The intake of nitrates decreased, and the use of statins increased (6.7% versus 13.9%, respectively, p&gt;0.05). AMI as the outcome of ACS was almost the same in both men and women. A downward trend in myocardial Q-infarction (p&gt;0.05) was found. Taking dual antiplatelet therapy and ACE inhibitors were more often recommended at discharge and taking nitrates and any diuretics was less common. Statins intake did not change. Conclusion. The “portrait” of a hospitalized ACS patient changed somewhat over 4 years: the frequency of the history of coronary heart disease significantly decreased, and the frequency of hypertension increased. The presence and significance of risk factors such as hypercholesterolemia and adverse heredity cannot be assessed as before. The frequency of use of antiplatelet agents and statins increased in prehospital therapy; however, in general, a smaller proportion of patients requiring statins took them. The proportion of AMI patients among ACS ones did not change over the study period

On a linear differential game of optimal approach of many pursuers with one evader

We consider a differential game of approach of many pursuers and one evader. The motions of all players are described by linear systems of the same type. Control functions of players are subject to integral constraints. The duration of the game is fixed. The payoff functional of the differential game is the minimum of the distances between the evader and the pursuers when the game terminates. The pursuers try to minimize the payoff functional, and the evader tries to maximize it. We obtain estimates for the payoff functional of the game, which can be guaranteed by players and explicitly describe the strategies of the players. From here we obtain that in some specific cases the value of the game exists, and optimal strategies can be constructed. An illustrative example is considered

Challenges of Statin Therapy in Clinical Practice (According to Outpatient Register «PROFILE» Data)

Aim. To identify the main problems of statin therapy in patients with high and very high cardiovascular (CV) risk in real clinical practice.Material and methods. The general information of the study was based on data from 2,457 patients who were included in the register before November 30, 2020: 1,250 men (50.9%) and 1,207 (49.1%) women. A more detailed analysis was performed for groups of patients with high          and very high CV risk who had indications for statin treatment at the time of inclusion in the register: out of 2457 patients, 1166 people had very high CV risk, 395 was at high CV risk (a total of 1561 people, the average age of patients was 64.4±11.0 years).Results. Information on the parameters of the lipidogram – the level of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) was available in 1918 (78.1%) and 1546 (62.9%) patients, respectively. Of 1561 patients with high and very high CV risk, TC and LDL-C levels were analyzed in 1221 (78.2%) and 956 (61.2%) cases, statistically significantly more often in patients with high CV risk (p&lt;0.05). Statins were recommended only to 823 (52.7%) patients with high and very high CV risk. Patients with very high CV risk received such appointments 4 times more often than patients with high CV risk: odds ratio (OR) 4.2; 95% confidence interval (CI) 3.2-5.3 (p&lt;0.001). Doctors preferred atorvastatin in prescriptions (n=456, 55.4%), rosuvastatin (n=244, 29.7%) and simvastatin (n=121, 14.7%) were in second and third places. The target level of LDLC was 2 times more often achieved in patients with high CVR, compared with patients with very high CV risk: OR = 2.0, 95% CI 1.4-3.0 (p&lt;0.001).Conclusion. The main problems of statin treatment in real clinical practice remain the non-assignment of these drugs to patients who have indications for such therapy and the failure to achieve the target levels of lipidogram indicators, which may probably be due to the clinical inertia of doctors regarding titration of statin doses, and in some cases caused by the choice of drugs that are not the most effective in reducing LDL cholesterol. Patients with very high CV risk are 4 times more likely to receive a recommendation to take statins compared to patients with high CV risk, but the target level of LDL cholesterol is reached in them 2 times less often