Factors determining phage stability/activity: challenges in practical phage application

Introduction: Phages consist of nucleic acids and proteins that may lose their activity under different physico-chemical conditions. The production process of phage formulations may decrease phage infectivity. Ingredients present in the preparation may influence phage particles, although preparation and storage conditions may also cause variations in phage titer. Significant factors are the manner of phage application, the patient’s immune system status, the type of medication being taken, and diet.

Areas covered: We discuss factors determining phage activity and stability, which is relevant for the preparation and application of phage formulations with the highest therapeutic efficacy. Our article should be helpful for more insightful implementation of clinical trials, which could pave the way for successful phage therapy.

Expert opinion: The number of naturally occurring phages is practically unlimited and phages vary in their susceptibility to external factors. Modern methods offer engineering techniques which should lead to enhanced precision in phage delivery and anti-bacterial activity. Recent data suggesting that phages may also be used in treating nonbacterial infections as well as anti-inflammatory and immunomodulatory agents add further weight to such studies. It may be anticipated that different phage activities could have varying susceptibility to factors determining their actions.     

Fatty acid changes help to better understand regression of nonalcoholic fatty liver disease

AIM: To investigate whether liver steatosis reduction due to a six-month dietary intervention results in significant changes in the concentrations of fatty acids.METHODS: A group of 35 Caucasian individuals diagnosed with different levels of steatosis were prospectively enrolled in the present study.Analysis of the fatty acid profiles was performed according to changes in liver steatosis(liver steatosis reduction by one or two degrees) after a six-month dietary intervention.The diet helped reduce body mass in obese and overweight patients,and stabilize both glycemia and dyslipidemia.Fatty acids were extracted according to the Folch method and analyzed by gas chromatography.RESULTS: This study showed significant changes in fatty acid profiles in patients who had reduced liver steatosis by one as well as two degrees.A reduction in liver steatosis by one degree caused a significant increase in the level of the n-3 family: eicosapentaenoic acid(P < 0.055),docosapentaenoic acid-C 22:5(P < 0.05) and docosahexaenoic acid(P < 0.05).A reduction in liver steatosis by two degrees caused a significant decrease in serum palmitoleic acid-C 16:1(P < 0.05).CONCLUSION: Liver steatosis reduction is associated with changes in fatty acid profiles,and these changes may reflect an alteration in fatty acid synthesis and metabolism.These findings may help better understand regression of nonalcoholic fatty liver disease.     

Microbiological quality of non-sterile pharmaceutical products

In microbiological terms, pharmaceutical products can be divided into two groups: sterile and non-sterile. Non-sterile drugs must satisfy the appropriate microbiological purity criteria which are included in pharmacopoeial monographs. Pharmacopoeial studies are prepared specifically with a view to ensuring that the medicinal product is therapeutically effective and safe for the patient. The analysis comprised the results of microbiological purity tests performed before the products are marketed. Total of 1285 samples of non-sterile drugs manufactured by different pharmaceutical plants in Polish were taken into study. The microbiological quality of drugs was assessed in accordance with the criteria included in the European Pharmacopoeia (EP). An analysis of test results demonstrated that the percentage of non-compliant samples was 1.87%. The groups of drugs, which the most often did not satisfy EPs’ requirements, were drugs containing raw materials of natural origin (5.7%). The samples of studied drugs that did not meet the criteria contained in EP, exceed the maximum allowable microbiological count limits and contained microbes whose presence is prohibited. The most common non-compliance was the excessive levels of the maximum acceptable fungal count (n = 12) and the excessive the maximum acceptable aerobic microbial count (n = 10).     

Prediction of AF in Heart Failure With Preserved Ejection Fraction: Incremental Value of Left Atrial Strain

ObjectivesThis study sought to identify the factors associated with incident atrial fibrillation (AF) in a well-characterized heart failure with preserved ejection fraction (HFpEF) population, with special focus on left atrial (LA) strain.BackgroundAF is associated with HFpEF, with adverse consequences. Effective risk evaluation might allow the initiation of protective strategies.MethodsClinical evaluation and echocardiography, including measurements of peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA volume index (LAVI), were obtained in 170 patients with symptomatic HFpEF (mean age, 65 ± 8 years), free of baseline AF. AF was identified by standard 12-lead electrocardiogram, review of relevant medical records (including Holter documentation), and surveillance with a portable single-lead electrocardiogram device over 2 weeks. Results were validated in the 103 patients with HFpEF from the Karolinska-Rennes (KaRen) study.ResultsOver a median follow-up of 49 months, incident AF was identified in 39 patients (23%). Patients who developed AF were older; had higher clinical risk scores, brain natriuretic peptide, creatinine, LAVI, and LV mass; lower LA strain and exercise capacity; and more impaired LV diastolic function. PACS, PALS, and LAVI were the most predictive parameters for AF (area under receiver-operating characteristic curve: 0.76 for PACS, 0.71 for PALS, and 0.72 for LAVI). Nested Cox regression models showed that the predictive value of PACS and PALS was independent from and incremental to clinical data, LAVI, and E/e’ ratio. Classification and regression trees analysis identified PACS ≤12.7%, PALS ≤29.4%, and LAVI >34.3 ml/m² as discriminatory nodes for AF, with a 33-fold greater hazard of AF (p < 0.001) in patients categorized as high risk. The classification and regression trees algorithm discriminated high and low AF risk in the validation cohort.ConclusionsPACS and PALS provide incremental predictive information about incident AF in HFpEF. The inclusion of these LA strain components to the diagnostic algorithm may help guide screening and further monitoring for AF risk in this population.     

Assessment of postural stability in women with hip osteoarthritis: A case–control study

Objective

The aim of the study was to assessment the impact of hip osteoarthritis on postural stability.