Blackberry Leaves as New Functional Food? Screening Antioxidant, Anti-Inflammatory and Microbiological Activities in Correlation with Phytochemical Analysis.

Blackberry fruits are recognized as functional foods while blackberry leaves are outside this classification and they also contain active compounds with health-promoting potential. Therefore, the aim of this study was the phytochemical analysis of blackberry leaves of varieties (Chester, Loch Ness, Loch Tay and Ruczaj) and screening of their biological activity (antioxidant potential, possibility of inhibition of enzymes, anti-inflammatory and microbial activity). The following compounds from selected groups: phenolic acids (caffeic acid, ellagic acid, gallic acid, syringic acid), flavonols (quercetin, kaempferol) and their glycosides (rutin, isoquercetin, hyperoside) and flavon-3-ols (catechin, epicatechin) were chromatographically determined in the aqueous and hydroalcoholic leaves extracts. All tested blackberry leaves extracts showed antioxidant effects, but the highest compounds content (TPC = 101.31 mg GAE/g) and antioxidant activity (e.g., DPPH IC50 = 57.37 µg/mL; ABTS IC50 = 24.83 µg/mL; CUPRAC IC50 = 62.73 µg/mL; FRAP IC50 = 39.99 µg/mL for hydroalcoholic extracts) was indicated for the Loch Tay variety. Blackberry leaf extracts' anti-inflammatory effect was also exceptionally high for the Loch Tay variety (IC50 = 129.30 µg/mL), while leaves extracts of the Loch Ness variety showed a significant potential for microbial activity against Lactobacillus spp. and Candida spp. Summarizing, the best multidirectional pro-health effect was noted for leaves extracts of Loch Tay variety.

Cyclodextrin as Functional Carrier in Development of Mucoadhesive Tablets Containing Polygoni cuspidati Extract with Potential for Dental Applications.

Polygoni cuspidati root is a resveratrol-rich source with anti-inflammatory, angiogenic and neuroprotective effects. The raw material was standardized for the content of resveratrol, for which there is a special justification for administration within the oral mucosa. To improve the solubility of resveratrol and to assure its high content in plant material, an ultrasound-assisted extraction method was applied. The addition of cyclodextrin was found to increase the extraction efficiency of resveratrol (from 13 to 297 µg per 1 g of plant material in case of 50% ethanol extracts) and enhanced its antioxidant activity as compared to pure Polygoni cuspidati extract/resveratrol. Cyclodextrin plays the role of a functional extract regarding technological properties (increasing the extraction of resveratrol from the extract, improving mucoadhesive properties). Therefore, the aim of this study was to develop mucoadhesive tablets containing combinations of the Polygoni cuspidati extract with a cyclodextrin carrier for buccal delivery. The tests sequentially included extract preparation and characterization of its physical and biological properties and then formulation studies with a broad description of the prototype properties. The test results indicate that cyclodextrin increases the efficiency of resveratrol extraction from Polygoni cuspidati rhizome, which is a rich source of resveratrol, and its extract enclosed in a mucoadhesive tablet guarantees prolonged action at the site of administration.

Potential Salivary Markers for Differential Diagnosis of Crohn's Disease and Ulcerative Colitis.

The properties of the saliva of patients with inflammatory bowel disease (IBD) are poorly recognized. Likewise, the diagnostic potential of saliva for differentiating various forms of IBD is largely unexplored. Therefore, we compared the concentrations of several parameters in unstimulated whole mixed saliva collected in a standardized manner from patients with active IBD unresponsive to conventional therapy. The samples were received from 27 patients with Crohn's disease (CD), 24 patients with ulcerative colitis (UC), and 51 healthy individuals. Compared to the controls, the salivary concentrations of S100A8/calprotectin, myeloperoxidase, and IgA were significantly decreased in both CD and UC patients. In addition, patients with UC had decreased levels of TNF-R1 and decreased catalase activity. Interestingly, the concentrations of myeloperoxidase and TNF-R1 showed a high differentiation potential for CD and UC (AUC = 0.690 and 0.672, respectively). All these findings are discussed in the context of host defense in the oral cavity, patients' prior treatment regimens, and smoking habits.

Resistance of IoT Sensors against DDoS Attack in Smart Home Environment.

Smart devices along with sensors are gaining in popularity with the promise of making life easier for the owner. As the number of sensors in an Internet of Things (IoT) system grows, a question arises as to whether the transmission between the sensors and the IoT devices is reliable and whether the user receives alerts correctly and in a timely manner. Increased deployment of IoT devices with sensors increases possible safety risks. It is IoT devices that are often misused to create Distributed Denial of Service (DDoS) attacks, which is due to the weak security of IoT devices against misuse. The article looks at the issue from the opposite point of view, when the target of a DDoS attack are IoT devices in a smart home environment. The article examines how IoT devices and the entire smart home will behave if they become victims of a DDoS attack aimed at the smart home from the outside. The question of security was asked in terms of whether a legitimate user can continue to control and receive information from IoT sensors, which is available during normal operation of the smart home. The case study was done both from the point of view of the attack on the central units managing the IoT sensors directly, as well as on the smart-home personal assistant systems, with which the user can control the IoT sensors. The article presents experimental results for individual attacks performed in the case study and demonstrates the resistance of real IoT sensors against DDoS attack. The main novelty of the article is that the implementation of a personal assistant into the smart home environment increases the resistance of the user's communication with the sensors. This study is a pilot testing the selected sensor sample to show behavior of smart home under DDoS attack.

Electron Paramagnetic Resonance of a Single NV Nanodiamond Attached to an Individual Biomolecule.

Electron paramagnetic resonance (EPR), an established and powerful methodology for studying atomic-scale biomolecular structure and dynamics, typically requires in excess of 10(12) labeled biomolecules. Single-molecule measurements provide improved insights into heterogeneous behaviors that can be masked in ensemble measurements and are often essential for illuminating the molecular mechanisms behind the function of a biomolecule. Here, we report EPR measurements of a single labeled biomolecule. We selectively label an individual double-stranded DNA molecule with a single nanodiamond containing nitrogen-vacancy centers, and optically detect the paramagnetic resonance of nitrogen-vacancy spins in the nanodiamond probe. Analysis of the spectrum reveals that the nanodiamond probe has complete rotational freedom and that the characteristic timescale for reorientation of the nanodiamond probe is slow compared with the transverse spin relaxation time. This demonstration of EPR spectroscopy of a single nanodiamond-labeled DNA provides the foundation for the development of single-molecule magnetic resonance studies of complex biomolecular systems.

PHARMACEUTICAL CARE FORM APPLICATION IN ELDERLY PATIENTS RESEARCH.

Many patients, especially elderly, very often don't inform family physicians about drugs prescribed by other specialist and use a number of preparations to self-medicate. These actions may supply negative consequences in recovery process and can be significantly reduced through the implementation of a well-run pharmaceutical care (PC) in the community pharmacy. Therefore, it is necessary to design proper PC documentation, which allows for comprehensive gathering information needed to carry out the analysis of relevant factors impacting on the prescribed pharmacotherapy effectiveness. The aim of this study was to develop the proper documentation to conduct PC in community pharmacy and verification of its correctness in the group of elderly patients, who is receiving treatment from family physician and additionally at least two specialized doctors. Also an assessment of PC implementation validity as a specialized service was presented. A study was carried out from January 2014 to June 2015. The research covered 54 elderly (41.0% men and 59.0% women) in Jarocin (Poland). Pharmacist was filling in the designed PC form, which subsequently was analyzed mainly for pharmacotherapy problems. The study indicated that 48.1% of patients were counselled by at least 3 specialists; 66.7% of patients were treated by cardiologist and 55.6% by the ophthalmologist; 75.9% of participants had hypertension. 42.6% of the patients used 10 or more pharmaceuticals and 24.1% took 8 or 9 drugs. Moreover, 20.4% of participants used drugs irregularly and 7.4% of them took too low doses of medications. Additionally, during the pharmacotherapy analysis, very significant and significant drug-drug interactions were noticed (1.1% and 18.4%, respectively). Very significant drug-food interactions occurred in 1.4% cases and significant in 3.3% cases. Total number of detected interactions were 553. The substantial analysis of participants' data allowed for 48 patients selection for pharmaceutical counselling. Six patients were involved into the group where PC process was reasonable. These patients often used 10 or more drugs (p = 0.0026), discontinued using medication without doctor consulting (p = 0.0201) and did not follow up the prescribed pharmacotherapy (p = 0.0351). This study provides new data about implementation of PC in Poland. The designed PC documentation may be helpful for proper analysis of the patient's pharmacotherapy to avoid drug problems and to improve elderly patients' quality of life. This project may contribute to PC implementation in Polish community pharmacy.

PHYSICIANS' VALUATION OF INDIVIDUAL MEDICATION MANAGEMENT SYSTEM (IMMS) IMPLEMENTATION IN POZNAN (POLAND) COMMUNITY PHARMACIES.

The reason of growing Pharmaceutical Care (PC) popularity in Poland and all over the world in recent years is connected with a new idea which separates pharmacists from a stereotype of drug store, dealing only with issuing medicines in adequate doses. There is an intention of emphasizing their qualifications and maximizing the use of them. One of the essential part of PC is preparing Individual Medication Management System (IMMS) which may provide individualized pharmacotherapy for patient. The aim of the study was to assess the physicians' opinion about implementation of IMMS in Polish community pharmacies and to evaluate physician-pharmacist cooperation. A cross sectional study was carried out from April 2013 to December 2013 by a pharmacist (authors' of the study). The survey covered 103 physicians (35.9% men and 64.1% women) providing medical services in Poznan. The respondents obtained an anonymous questionnaire with a brief information about IMMS. The results of the study confirmed that 90.3% of physicians would recommend IMMS to their patients. They believed that 72.8% of the patients would be interested in this service. According to 74.8% of doctors, especially with a specialization in cardiology, family medicine, and without specialty, IMMS might contribute to the PC development (p < 0.0001). The respondents (56.3%) confirmed their collaboration with at least 1 pharmacist and 79.6% declared the possibility of the cooperation by using IMMS. This study provides new data about implementation of IMMS in Poland. This innovatory service could be the chance both for patient and physicians to increase the safety and effectiveness of pharmacotherapy and for pharmacists who are intended to highlight their role as a part of health care system. The physicians' positive opinion provide the opportunity to implement IMMS in Polish community pharmacies.

Individual medication management system (IMMS) implementation in pharmacists' opinion.

Many countries of the world including Poland, are taking actions for improving the role of the pharmacist as a health care professional. One of those is implementation of pharmaceutical care (PC), as a documented specialist medical service, which also includes pharmacist interventions, such as preparing Individual Medication Management System (IMMS), to enhance patient's adherence. Because of the chance to monitor the dosage and to detect and prevent drug problems occurrence, IMMS is thought to be an opportunity for individualized, effective and safe patient's pharmacotherapy. The aim of the study was to define pharmacists' attitudes toward IMMS. The study included also the evaluation of pharmacist-physician cooperation to determine whether IMMS can improve partnership among health care professionals for proper patient's care. The survey was conducted in Poznan, between June 2011 and March 2012. An anonymous questionnaire was delivered personally to pharmacists. Each questionnaire was provided with a short information brochure attached and presentation of demos how to use IMMS. The survey covered 129 pharmacists (76.7% women and 23.3% men) where 48.8% had up to 5 years length of service as a pharmacist, 24.8% - 6-10 years, 14.9% - 11-20 years and 11.5% - 21 and more years. Most of the participants did not have specialization (80.6%) and only 5.4% had Ph.D. degree. Survey confirmed that 64.8% of pharmacists (p < 0.0001), mainly with the shortest length of service (p = 0.02268) and without specialty (p = 0.00244) didn't cooperate with physicians, but 68.8% of respondents emphasized that the range of cooperation could increase by IMMS application (p < 0.00001). About 50.0% of respondents' considered that patients would be interested in IMMS usage (p = 0.00079) and in 71.9% opinions, it would attach the patient to specific community pharmacy (p < 0.00001). This statement was confirmed by respondents with the shortest length of services (p = 0.00659). Proposed dosing system also improved patient's care serving by family or carers in pharmacists' opinion (p < 0.00001). A majority of pharmacists (85.3%) indicated also that IMMS would have a positive influence on PC implementation in Poland (p < 0.00001) and 69.0% of them confirmed that this service should be refunded by the National Health Fund (p < 0.00001). According to the scale of non-compliance, implementation of IMMS as a part of PC can be a chance both for patients and their physicians to increase the safety and effectiveness of therapy and for pharmacists, who are intended to highlight their role as a part of health care system.

Histone H3 phosphorylation near the nucleosome dyad alters chromatin structure.

Nucleosomes contain ∼146 bp of DNA wrapped around a histone protein octamer that controls DNA accessibility to transcription and repair complexes. Posttranslational modification (PTM) of histone proteins regulates nucleosome function. To date, only modest changes in nucleosome structure have been directly attributed to histone PTMs. Histone residue H3(T118) is located near the nucleosome dyad and can be phosphorylated. This PTM destabilizes nucleosomes and is implicated in the regulation of transcription and repair. Here, we report gel electrophoretic mobility, sucrose gradient sedimentation, thermal disassembly, micrococcal nuclease digestion and atomic force microscopy measurements of two DNA-histone complexes that are structurally distinct from nucleosomes. We find that H3(T118ph) facilitates the formation of a nucleosome duplex with two DNA molecules wrapped around two histone octamers, and an altosome complex that contains one DNA molecule wrapped around two histone octamers. The nucleosome duplex complex forms within short ∼150 bp DNA molecules, whereas altosomes require at least ∼250 bp of DNA and form repeatedly along 3000 bp DNA molecules. These results are the first report of a histone PTM significantly altering the nucleosome structure.

Physicians' and patients' valuation of pharmaceutical care implementation in Poznan (Poland) community pharmacies.

Implementation of pharmaceutical care (PC) in Poland is of great importance to patients, who, on the one hand, often follow complex pharmacological treatment regimens recommended by several physicians of different specialties, and, on the other, take up the decision on self-treatment due to availability of OTC medications. The aim of the present study was to assess the opinion of both patients and physicians about implementation of PC service in Polish community pharmacies. A cross sectional study was carried out from September 2009 to September 2010 by a pharmacist (author of the study) on the basis of an anonymous questionnaire, where demand of physicians (n = 104) and patients (n = 202) for implementation of PC in a community pharmacy was assessed. The study was planned to determine the relationship between implementation of PC, cost and time of this service and patients' and physicians' socio-economic information. Responding patients (85.64%) and physicians (76.92%) unanimously confirmed the need for implementation of PC. Most people convinced of the service implementation were 88.89% of physicians under the age of 35 and all the respondents were over 65 years of age (p = 0.027), just as 93.33% with service lesser than 5 years and 73.68% of respondents working a maximum of 20 years (p = 0.023). Mainly according to 90.00% of physicians with specialty in internal medicine and 92.59% of physicians of the group "Others" (p = 0.012), PC should be implemented in pharmacies. Women more frequently than men reckoned that appointments with a pharmacist should last up to 15 min (p = 0.012). According to 77.78% of the youngest physicians and 83.33% of the oldest ones, appointments should last from 5 to 15 min (p = 0.049), and a similar opinion was shared by 80.77% of physicians without specialty and 77.78% of physicians of the group "Others" (p = 0.0009). According to patients, the mean cost of the visit should be USD 7. Physicians most often assessed the mean cost of the appointment at USD 14. This study provides new data about implementation of PC in Poland. The increased patients' and physicians' willingness to benefit from this service provides pharmacists with opportunities to develop PC in community pharmacies.

Individual medication management system (IMMS) as a proposition of obeying the doctor's recommendation with pharmacist cooperation.

The pharmacist is an expert with the knowledge of drugs, who has a possibility to follow the patient's individual pharmacotherapy, which is the basis of the pharmaceutical care programme. The implementation of the Individual Medication Management System (IMMS) may be one of the proposals which will enable an analysis of the course of pharmacotherapy and elimination of drug problems, which are the chief goals of pharmaceutical care. In order to determine community pharmacy patients' degree of interest in the IMMS and to evaluate the degree of patients' discipline concerning the application of doctors' recommendations they were given an anonymous questionnaire. The research was done from August 2009 to May 2010 on a sample of 179 people selected at random. They were patients of community pharmacies in Poznan, where 70% were women and 30% were men, all of them aged between 20 and 85 years. The individual age groups were: 20-40 years--27.0%, 41-50 years--10.8%, 51-64 years--43.6%, 65 years or more--18.6%. The patients' education was as follows: primary--4.7%, vocational--8.0%, secondary--31.0%, incomplete university--12.0% and university--44.3%. The chi2 and Fisher-Freeman-Halton tests were used for statistical analysis of the results. Each time the level of statistical significance was assumed at p < 0.05. The collected results confirmed the fact that there is a higher number of specialists involved in patients' treatment with their age (p = 0.001), which indirectly leads to a higher number of prescribed drugs (p = 0.00000002). It was proved that more than 90% of the patients aged over 50 years take the prescribed drugs for more than a year (p = 0.00000002). The analysis confirmed the fact that there are mostly men which do not abide the indications concerning the dosage regimen (p = 0.049). The answers to the questions evaluating the patients' attitude to the IMMS revealed that 47.2% of the respondents indicate the advantages of the system. However, it was mostly women and respondents with university education that were the most interested in it. More than 50% of the patients aged 20-40 years and those aged over 65 years indicate the purposefulness of the systems. It is mainly the group aged 20-40 years that confirms facilitation in following the doctor's recommendations (p = 0.02). The respondents indicated their interest and confirmed the purposefulness of the IMMS mainly due to the fact that it helps to avoid drug-related problems resulting from omitting doses and helps to keep the dosage time and frequency in a long-term therapy. The research confirms the fact that individualized therapy will contribute to its higher efficacy, economy and safety.

[Aging of prokaryotic organisms]. / Starzenie sie organizmów prokariotycznych.

Until recently it was thought that aging is a characteristic feature only of cells and organisms of eukaryotic origin. Recent studies on Caulobacter crescentus showed that their dimorphic life cycle associated with asymmetric cell division leads to a gradual increase in the time needed for the development of new bacteria generations, which may reflect aging of this organism. Moreover, as shown in Escherichia coli, accelerated exhaustion of proliferative capacity and bacteria death are caused by inheritance of certain structures from the mother cell during cell division. A similar phenomenon, called 'conditional senescence', has been observed during the stationary phase of growth in liquid cultures. The aim of this paper is to present the current state of knowledge on the causes, mechanisms and evolutionary significance of aging in bacteria. Some issues associated with bacterial aging will be discussed in the context of similar phenomena occurring in eukaryotic cells.

Histone fold modifications control nucleosome unwrapping and disassembly.

Nucleosomes are stable DNA-histone protein complexes that must be unwrapped and disassembled for genome expression, replication, and repair. Histone posttranslational modifications (PTMs) are major regulatory factors of these nucleosome structural changes, but the molecular mechanisms associated with PTM function remains poorly understood. Here we demonstrate that histone PTMs within distinct structured regions of the nucleosome directly regulate the inherent dynamic properties of the nucleosome. Precise PTMs were introduced into nucleosomes by chemical ligation. Single molecule magnetic tweezers measurements determined that only PTMs near the nucleosome dyad increase the rate of histone release in unwrapped nucleosomes. In contrast, FRET and restriction enzyme analysis reveal that only PTMs throughout the DNA entry-exit region increase unwrapping and enhance transcription factor binding to nucleosomal DNA. These results demonstrate that PTMs in separate structural regions of the nucleosome control distinct dynamic events, where the dyad regulates disassembly while the DNA entry-exit region regulates unwrapping. These studies are consistent with the conclusion that histone PTMs may independently influence nucleosome dynamics and associated chromatin functions.

Peritoneal effects of intravenous iron sucrose administration in rats.

Intravenous iron supplementation is commonly used in uremic patients treated with peritoneal dialysis. Infusion of iron compounds results in various systemic noxious effects, mainly because of its prooxidant and proinflammatory actions. The authors studied how the intravenous infusion of iron sucrose (IS) affects intraperitoneal homeostasis in rats undergoing acute peritoneal dialysis. Experiments were performed on Wistar rats, which were infused intravenously with IS in a dose 10 mg/kg body weight or with normal saline in the controls. Simultaneously, 4-hour acute peritoneal dialysis was started. At the end of the dialysis, systemic and peritoneal inflammatory reaction and peritoneal permeability were evaluated. Compared with controls, rats exposed to IS showed increased dialysate iron concentration by +70%, P<0.001, and in the differential cell count, more eosinophils (+113%, P<0.05) and fewer macrophages (-16%, P<0.05) existed. In in vitro conditions, macrophages obtained from IS-treated rats released more tumor necrosis factor-alpha (TNF-alpha; +173%, P<0.05) upon stimulation with endotoxin. Additionally increased (+73%, P<0.01) dialysate elastase activity was found in IS-treated animals. Rats infused with IS demonstrated increased peritoneal permeability to total protein (+60%, P<0.001) as compared with control animals. When rats with simultaneous peritonitis received intravenous IS, ex vivo isolated peritoneal leukocytes generated more free radicals (+73%, P<0.05) than did cells harvested from control animals. It has been concluded that intravenous infusion of IS affects the intraperitoneal homeostasis in rats, moving it toward the inflammatory state. These changes may contribute to peritoneal damage.