Efficacy of interrupted cyclic treatment with prednisolone on cancer pain: a randomized crossover study

Background Interrupted cyclic treatment with a low oral dose of prednisolone combined with stepladder analgesics would reduce the pain scores in cancer patients with reported less side effects. Following ethical approval, 39 cancer patients were randomized to receive prednisolone 10 mg every other day or every 4th day for 4 successive weeks followed with tapering prednisolone by 2.5 mg every 4 days over 2 weeks after each interval, primary outcome visual analog score (VAS), and other secondary outcomes such as (A) patient demographics; (B) pain scores; brief pain inventory score (BPI), pain severity score (PSS), pain interference score (PIS), analgesia level score, pain level score (PLS), and pain management index (PMI)); and (C) patient safety (adverse effects) with interrupted cyclic treatment with low-dose prednisolone. Results Compared with baseline values, patients had statistically significant lower VAS and PSS pain scores at 14 and 28 days after starting the 2 days cyclic treatment with prednisolone. Patients had comparative VAS and PSS pain scores during the 4-day cyclic treatment with prednisolone. Compared with the 4-day cyclic treatment, patients in the 2-day cyclic treatment had significant statistically lower VAS pain scores at 28 days. Adverse effects showed no significant statistical differences during both study sequences. Conclusion Interrupted cyclic prednisolone 10 mg combined with stepladder analgesic regimen is effective and safe in terms on improved quality of analgesia for 28 days in cancer patients more when used every 2nd day than every 4th day with appetite improvement during both. Trial registration The study protocol was approved by the local Institutional Board Review Committee on 8-11-2019. The study was prospectively registered with the www.clinicaltrials.gov

rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure

Background Pseudomonas aeruginosa is a notorious opportunistic pathogen causing various types of biofilm-related infections. Biofilm formation is a unique microbial strategy that allows P. aeruginosa to survive adverse conditions such as antibiotic treatment and human immune clearance. Results In this study, we experimentally evolved P. aeruginosa PAO1 biofilms for cyclic treatment in the presence of high dose of imipenem, and enriched hyperbiofilm mutants within six cycles in two independent lineages. The competition assay showed that the evolved hyperbiofilm mutants can outcompete the ancestral strain within biofilms but not in planktonic cultures. Whole-genome sequencing analysis revealed the hyperbiofilm phenotype is caused by point mutations in rpoS gene in all independently evolved mutants and the same mutation was found in P. aeruginosa clinical isolates. We further showed that mutation in rpoS gene increased the intracellular c-di-GMP level by turning on the expression of the diguanylate cyclases. Mutation in rpoS increased pyocyanin production and virulence in hyperbiofilm variants. Conclusion Here, our study revealed that antibiotic treatment of biofilm-related P. aeruginosa infections might induce a hyperbiofilm phenotype via rpoS mutation, which might partially explain antimicrobial treatment failure of many P. aeruginosa biofilm-related infections.

Influtnce analysis of 09Г2С and 30MnB5 steels thermo cyclic treatment on strength characteristics of road construction machines working bodies

Introduction. The ways of increasing the reliability of road construction machinery operation are considered. As a result, an option is proposed to replace the used 09Г2С steel with 30MnB5 boron steel. Using the example of a motor grader blade, the force effects on this working body of the road construction machinery are analyzed. In order to increase the level of physical and mechanical characteristics of 09Г2С and 30MnB5 steels, they are additionally exposed to thermo cyclic treatment. The experimental studies about the influence of this type thermal action on the structure and properties of steels are described. The comparative analysis of the obtained characteristics allows making a conclusion about the possibility of the considered replacement.Materials and methods. Through the metallographic analysis the influence of the number of thermal effects cycles on the grain size of steel is investigated. Alongside a set of physical and mechanical characteristics of these steels was determined at various stages of the thermo cyclic treatment.Results. It was determined that an increasing the level of physical and mechanical characteristics of the studied steels is possible through the use of thermo cyclic treatment. This is achieved by producing a fine-grained metal structure with a higher strength. The dependence of the tensile strength and yield strength of the steels under investigation on the number of cycles of thermal action is considered. Some correlation relationships were selected to describe these dependencies. The relationship between the yield stress and ultimate strength of 09Г2С and 30MnB5 steels and the grain size is considered. All investigated dependencies are presented in graphical form.Discussion and conclusion. Based on a comparative analysis of the complex of physical and mechanical characteristics, the conclusion about the possibility of replacing 09Г2С steel with 30MnB5 steel was made.

RpoS Mutation Leads to Prolonged Biofilm Mode of Growth and a Higher Fitness in Pseudomonas Aeruginosa Biofilms

BackgroundPseudomonas aeruginosa is a notorious opportunistic pathogen causing various biofilm-related infections. Biofilm formation is a unique microbial strategy that allows P. aeruginosa to survive adverse conditions such as antibiotic treatment and human immune responses. ResultsIn this study, we experimentally evolved P. aeruginosa PAO1 biofilms for cyclic treatment in the presence of high dose of imipenem, and enriched hyperbiofilm mutants within six cycles in two independent lineages. The competition assay showed the evolved hyperbiofilm mutants can outcompete the ancestral strain within biofilm by prolonging the biofilm mode of growth but not in planktonic cultures. Whole-genome sequencing analysis revealed the hyperbiofilm phenotype is caused by point mutations in rpoS gene in all independently evolved mutants and the same mutation was found in P. aeruginosa clinical isolates. We further showed that mutation in rpoS enhanced biofilm formation by prolonging the biofilm mode of growth and elevating the intracellular c-di-GMP level. Mutation in rpoS increased pyocyanin production and virulence in both P. aeruginosa laboratory strains and clinical isolates. ConclusionHere, our study revealed that antibiotic treatment of biofilm-related P. aeruginosa infections might induce a hyperbiofilm phenotype via rpoS mutation, which might partially explain antimicrobial treatment failure of many P. aeruginosa biofilm-related infections.

Prediction of suitable heat treatment for H13 tool steels by application of thermal shock fatigue cycle

In industry, thermally shocked components lead to early failures and unexpected breakdowns during production resulting in huge losses in profit. Thus, the present study investigates the as-received, hardened and hardened and nitrogen treated H13 tool steels subjected to a thermal shock gradient similar to the actual industrial applications. The thermal shock gradients were created by using an in-house-built thermal shock fatigue cyclic treatment machine. The effect of thermal shock fatigue cyclic treatments at 1000 and 2000 thermal shock cycles in hot and molten metal chambers was noticed. All the thermal shock fatigue cyclic-treated samples were analysed by hardness, X-ray diffraction, microscopy and magnetic tests. The interesting changes in hardness, distorted crystal structure and crack initiation were found to be different for differently treated H13 tool steel specimens. The molten aluminium was more prone to stick to the surface of as-received as well as hardened and nitrogen treated steel compared to the hardened H13 steel specimens, which would delay the crack initiation. The wear resistance properties of the hardened H13 steel specimens were found to be higher than as-received and hardened and nitrogen treated H13 steel specimens after thermal shock fatigue cyclic treatment. The loss in magnetic properties was significant for the hardened and hardened and nitrogen treated samples compared to as-received H13 tool steel specimens. Therefore, the present 1000 and 2000 thermal fatigue cycles for 30 s at 670 °C would be worthy to predict the proper heat treatment method to design the parameters as well as the life of die-casting components and to help in the economical production of casting.

A Study of Recycling Process of Cobalt-based Conversion Coating Formed on Aluminium Alloys

In this study, the influence of different cyclic treatment and reuse process on the performance of the conversion film was systematically studied by electrochemical test, surface characterization and determination of cobalt ions in the conversion solution, and new technology of chemical conversion of cobalt salts in aluminum alloys were determined. Mode A indicated the practice of cyclical processing of the test object in the original conversion solution, in which components of the circulation liquid were consumed continuously. After the first cycle, the Ecorr and Rp were – 691.8 V and 63.5 kΩ. In the later time, Rp was just about 13.0 kΩ, and the corrosion resistance of conversion film degraded progressively. Mode B represented the practice of adding to the original solution before cyclical processing of the test object, so that volume of the solution remains unchanged, and components of the circulation liquid kept increasing. RP increased from 9.3 kΩ to the 69.9 kΩ at the beginning of the cycle, followed by a slow descent, and content of cobalt in the film was stable, also higher than that under model A. This demonstrates that mode A has high utilization of the cobalt in the conversion solution in the early recycling, whereas mode B can prolong the cyclic service life of the conversion solution in circulation. After adding oxidants, as NaClO3, NaBrO3, H2O2, NaClO, and KMnO4, to the circulation liquid before recycling, the reuse and recycle ratio of cobalt reaches up to 41.3 %, and Rp can be promoted to123.2 kΩ at most. The life of the recycling was prolonged, while the costs of chemical conversion of cobalt were reduced.

Efficacy of cyclic therapy with terpinen-4-ol in Demodex blepharitis

Purpose To describe the effectiveness of cyclic treatment with terpinen-4-ol, a tea tree oil component, on Demodex blepharitis. Methods The presence of Demodex was determined by eyelash rotation as proposed by Mastrota. Schirmer test, tear breakup time, ocular surface disease index, lid margin score, meibomian gland expressibility score, and Oxford grade were performed. Patients were advised to apply heat followed by terpinen-4-ol soaked wipes to eyelids twice a day for 2 weeks. At the end of 2 weeks, treatment was interrupted for 7–10 days. The same treatment was repeated once again. The patients were examined after the first and second cycle of treatment and after 1 year. Results There was a statistically significant improvement in Schirmer test (10.37 ± 4.73 and 13.13 ± 3.44 mm/5 min), tear breakup time (6.47 ± 3.31 and 7.6 ± 2.89 s), ocular surface disease index (47.94 ± 19.77 and 34.28 ± 13.40), lid margin score (3.2 ± 0.7 and 2.63 ± 0.71), meibomian gland expressibility scores (1.93 ± 0.64 and 1.4 ± 0.67), and Oxford grade (0.9 ± 0.8 and 0.5 ± 0.63) after the first cycle of treatment ( p < 0.05). The improvement in symptoms and tear function tests of the patients after the second cycle was significantly better than in pre-treatment levels. At 12-month follow-up, symptoms of two patients (93%) relapsed. Conclusion The administration of terpinen-4-ol to the eyelid margins in a cyclic manner in Demodex blepharitis is effective against adult and hatching Demodex and breaks the vicious cycle.