Showing papers in "Current Pharmaceutical Biotechnology in 2019"

Healthcare-Associated Infections Due to Multidrug-Resistant Organisms: a Surveillance Study on Extra Hospital Stay and Direct Costs.

Abstract: BACKGROUND The increasing antimicrobial resistance poses a challenge to surveillance systems and raises concerns about the impact of multidrug-resistant organisms on patient safety. OBJECTIVE The study aimed to estimate extra hospital stay and economic burden of infections due to alert organisms - mostly multidrug-resistant - in a teaching hospital. METHODS The present retrospective matched cohort study was conducted based on the analysis of hospital admissions at Sant'Andrea Teaching Hospital in Rome from April to December 2015. Extra hospital stay was the difference in the length of stay between each case and control. All the patients developing an infection due to an alert organism were considered cases, all others were eligible as controls. The costs of LOS were evaluated by multiplying the extra stay with the hospital daily cost. RESULTS Overall, 122 patients developed an infection due to alert organisms and were all matched with controls. The attributable extra stay was of 2,291 days (mean 18.8; median 19.0) with a significantly increased hospitalization in intensive care units (21.2 days), bloodstream infections (52.5 days), and infections due to Gram-negative bacteria (mean 29.2 days; median 32.6 days). Applying the single day hospital cost, the overall additional expenditure was 11,549 euro per patient. The average additional cost of antibiotic drugs for the treatment of infections was about 1,200 euro per patient. CONCLUSION The present study presents an accurate mapping of the clinical and economic impact of infections attributable to alert organisms demonstrating that infections due to multidrug-resistant organisms are associated with higher mortality, longer hospital stays, and increased costs. Article Highlights Box: The increasing antimicrobial resistance poses a challenge for surveillance systems and raises concerns about the impact of multidrug-resistant organisms on patient safety. • Healthcare-associated infections (HAIs) have historically been recognized as a significant public health problem requiring close surveillance. • Despite several and reliable findings have been achieved on clinical issues, our knowledge on the economic impact of healthcare-associated infections due to multidrug-resistant organisms needs to be widened. • Estimating the cost of infections due to multidrug-resistant organisms in terms of extra hospital stay and economic burden is complex, and the financial impact varies across different health systems. • Evaluations of social and economic implications of hospital infections play an increasingly important role in the implementation of surveillance systems. • The costs of infection prevention and control programs and dedicated personnel are relatively low and self-sustainable when efficient.

Medicinal Plant Compounds for Combating the Multi-drug Resistant Pathogenic Bacteria: A Review.

Abstract: Background Globally, people utilize plants as the main source of remedy to heal various ailments. Medicinal plants have been utilized to treat ailments since the invention of modern scientific systems of medicine. The common remedy of infectious diseases mainly depends on the inhibition capacity of compounds or killing potential. The issue may give a clue for the development of a novel antimicrobial agent. Methods Currently, microorganisms which are resistant towards antibiotics are probably a matter of serious concern for the overall well-being of health. At the moment, new therapeutic targets aside from the microorganism wall-based activities are in progress. For instance, the autoinducer molecules produced by the quorum sensing system are used to control antibiotic resistance and biofilm formation. Results This therapeutic target is well-studied worldwide, however, the scientific data are not updated and only current studies started to gain insight into its perspective as a target to struggle against infectious diseases. Microbial resistance against antimicrobial compounds is a topic of serious concern in recent time. Conclusion Hence, this paper aims to confer a current overview of the novel compounds, quorum sensing, quorum quenching, biofilm formation in the development of antibiotic resistance and an update on their importance as a potential target for natural substances.

Ginger: A Novel Strategy to Battle Cancer through Modulating Cell Signalling Pathways: A Review.

Abstract: Numerous studies have been performed in understanding the development of cancer. Though, the mechanism of action of genes in the development of cancer remains to be explained. The current mode of treatment of cancer shows adverse effects on normal cells and also alter the cell signalling pathways. However, ginger and its active compound have fascinated research based on animal model and laboratories during the past decade due to its potentiality in killing cancer cells. Ginger is a mixture of various compounds including gingerol, paradol, zingiberene and shogaol and such compounds are the main players in diseases management. Most of the health-promoting effects of ginger and its active compound can be attributed due to its antioxidant and anti-tumour activity. Besides, the active compound of ginger has proven its role in cancer management through its modulatory effect on tumour suppressor genes, cell cycle, apoptosis, transcription factors, angiogenesis and growth factor. In this review, the role of ginger and its active compound in the inhibition of cancer growth through modulating cell signalling pathways will be reviewed and discussed.

Hyperglycemia and Diabetes Induced by Glucocorticoids in Nondiabetic and Diabetic Patients: Revision of Literature and Personal Considerations.

Abstract: Background Glucocorticoids are powerful and effective anti-inflammatory and immunosuppressive drugs. They have extensive use in the treatment of different diseases, even though their side effects, such as hypertension, osteoporosis and, in particular, diabetes, are well known. They can exacerbate hyperglycemia in patients with diabetes mellitus or facilitate the development of metabolic disease in apparently healthy subjects, the so-called steroid-induced diabetes mellitus. The last one is an independent risk factor for other complications associated with the use of glucocorticosteroids. Objectives We tried to clarify the physiopathology and the correct management of glucocorticoidsinduced diabetes, referring in particular to diabetic patients who have to take such drugs for long periods. Methods A thorough literature search was performed using Pubmed database to cover all relative reports, using combinations of keywords: diabetes mellitus, insulin, glucocorticoids therapy, dipeptidyl peptidase- 4 inhibitors (DPP-4 inhibitor), glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists), sodium-glucose co-transporter-2 inhibitors (SGLT-2 inhibitor), hyperglycemia, glucose-lowering drugs. Results & conclusion Glucocorticoids-induced diabetes is a harmful and underestimated problem when the therapeutic program is not correct and well planned. Screening or more stringent monitoring must always be suggested before starting with corticosteroids; moreover, the hypoglycemic therapy should be personalized, based on the severity of hyperglycemia, type of steroid used and patients' comorbidities. All the oral glucose-lowering drugs can be used, but insulin is the most studied drug and the medication recommended for severe hyperglycemia, for patients with pre-existing diabetes or for those patients who have to undergo prolonged therapy over time.

Valorization of Fruits by-products to Unconventional Sources of Additives, Oil, Biomolecules and Innovative Functional Foods.

Abstract: Owning to the increase in the world population as well as the consumer's awareness on the health benefits of consumption of fruits, the demand for both fresh and processed fruits has been increased. The by-product and waste streams generated from fruit processing industries are extremely diverse, owning mainly to different fruits varieties and the wide range of the processes employed towards the production of the end fruit-based products. Due to the increasing production and processing of fruits, disposal of waste and by-product streams has become a serious issue, since these materials are prone to microbial spoilage. Also, the inappropriate waste management practices pose severe environmental issues. Furthermore, the costs of drying and storage of fruit processing residues are economically limiting factors hindering their further exploitation. Therefore, fruit processing by-products such as peels, seeds and unused flesh are often utilized as fertilizers. On the other hand, plant residues contain biomolecules such as vitamins, proteins, minerals, antioxidants and aromatic oil. Recovery of bioactive compounds holds a great potential for their usage in food industry as functional ingredients and nutraceuticals or in pharmaceutical and in cosmetic applications. So, valorization of plant fruit processing by-products to high-value added compounds, constitute a promising alternative not only for addressing fruit residues management issues but also leading to the production of functional food products of high nutritional value, with several potential beneficial health effects. The aim of this paper is to highlight current trends in addressing environmental issues caused by the production of high volumes of specific categories of fruit processing waste streams by investigating their potential usage as natural raw materials for the recovery of valuable bioactive compounds (such as polyphenols, dietary fibers or aromatic oil). The extracted nutrients may be used in the industrial food sector for the production of functional foods, nutraceuticals or even as health promoting natural pharmaceutical ingredients or additives for the production of innovative enriched foods. Highlights: • Fruit processing by product streams are rich in bioactive compounds. • Integration of fruit by-products and waste streams to value added products such as additives, unconventional oil, bioactive compounds and novel functional products is a very interesting approach regarding fruit processing residues exploitation. • Recovering of biomolecules from fruit residues by non-thermal processes could lead to the efficient production of highly purified functional ingredients. • Negative-valued fruit processing residues could be recycled for the production of health promoting value added products.

Phenolic Acids Derivatives - Biotechnological Methods of Synthesis and Bioactivity

Abstract: Phenolic acids are secondary plant metabolites belonging to polyphenol classes, widely spread throughout the plant kingdom. The name "phenolic acids", in general, describes phenols that possess one carboxylic acid functionality and they could be divided into three major subclasses: hydroxybenzoic, hydroxycinnamic and hydroxyphenylacetic acids. The great interest in phenolic acids is associated with their high potential for food preservation (antioxidant and antimicrobial activity) and, last but not least, high therapeutic potential. The aim of this review is to summarise the current knowledge concerning phenolic acids and the topics discussed include natural sources of phenolic acids, biosynthesis and metabolism, health benefits of phenolic acids (first of all the antioxidant activity of dietary phenolics and also anticarcinogenic and anti-inflammatory effect), their antimicrobial activity for selected groups of bacteria and fungi (yeasts) and structural modifications of the molecule especially those increasing lipophilicity and improving solubility in lipids. Recent advances in the methods of enzymatic synthesis of phenolic acid derivatives are described and some conclusions referring to Structure-Property-Activity Relationships of phenolic acids, particularly important from the point of view of their pharmaceutical and nutritional applications, are discussed.

Antibody Therapy for the Control of Viral Diseases: An Update.

Abstract: The epidemiological impact of viral diseases, combined with the emergence and reemergence of some viruses, and the difficulties in identifying effective therapies, have encouraged several studies to develop new therapeutic strategies for viral infections. In this context, the use of immunotherapy for the treatment of viral diseases is increasing. One of the strategies of immunotherapy is the use of antibodies, particularly the monoclonal antibodies (mAbs) and multi-specific antibodies, which bind directly to the viral antigen and bring about activation of the immune system. With current advancements in science and technology, several such antibodies are being tested, and some are already approved and are undergoing clinical trials. The present work aims to review the status of mAb development for the treatment of viral diseases.

Antibacterial and Potential Antidiabetic Activities of Flavone C-glycosides Isolated from Beta vulgaris Subspecies cicla L. var. Flavescens (Amaranthaceae) Cultivated in Egypt.

Abstract: Background Diabetes mellitus is the most common disease in Egypt. In this context, Beta vulgaris subspecies cicla L. var. flavescens is an edible plant that has been used in traditional medicine as a therapy for treating some diseases. Objectives The current study was performed to evaluate the antibacterial and potential anti-diabetic activities of different extracts and isolated flavone C-glycoside compounds isolated from Beta vulgaris subspecies cicla L. var. flavescens leaves. Methods Phytochemical investigation of n-butanol extract led to the isolation of five phytoconstituents. Their structures were determined by spectroscopic tools, including 1D-NMR (1H- & 13C-NMR) and 2D-NMR (HMQC & HMBC) besides the comparison of the data with the literature. The extracts and phytoconstituents were evaluated in vitro for their activity against some bacterial pathogens, which represent prominent human pathogens, particularly in hospital settings. The antibacterial activity was examined against three Gram-positive bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis & Enterococcus faecalis) and five Gram-negative ones (Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella pneumoniae, Proteus mirabilis & Salmonella typhimurium) relative to Ciprofloxacin as a reference drug. Furthermore, the in vitro antidiabetic activity (Type II) was evaluated using the alpha-glucosidase inhibitory assay. Results Five flavone C-glycosides namely; Apigenin 8-C-β-D-glucopyranoside (vitexin) (1), 2''-Oxylopyranosylvitexin (2), acacetin 8-C-β-D-glucopyranoside (3), acacetin 8-C-α-L-rhamnoside (4), and 6,8-di-C-β-D-glucopyranosylapigenin (vecinin-II) (5) were isolated from n-butanol extract of B. vulgaris subspecies cicla L. var. flavescens. Compound 1 showed a promising antibacterial activity against most of the test bacterial strains with respect to the minimum inhibitory concentration values (MIC) ranged from 1.95 to 15.63 µg ml-1. On the other hand, compounds 1 and 3 demonstrated superior antidiabetic activities with IC50 values of 35.7 and 42.64 µg ml-1, respectively, while an inferior potential antidiabetic activity was recorded for compound 4 (IC50 = 145.5 µg ml-1) in comparison with Acarbose as a reference drug. Conclusion B. vulgaris L. is an edible plant, which could be used as a natural source of antibiotic and hypoglycemic drugs.

Blood Brain Barrier Permeability Prediction Using Machine Learning Techniques: An Update

Abstract: Blood Brain Barrier (BBB) is the collection of vessels of blood with special properties of permeability that allow a limited range of drug and compounds to pass through it. The BBB plays a vital role in maintaining balance between intracellular and extracellular environment for brain. Brain Capillary Endothelial Cells (BECs) act as vehicle for transport and the transport mechanisms across BBB involve active and passive diffusion of compounds. Efficient prediction models of BBB permeability can be vital at the preliminary stages of drug development. There have been persistent efforts in identifying the prediction of BBB permeability of compounds employing multiple machine learning methods in an attempt to minimize the attrition rate of drug candidates taking up preclinical and clinical trials. However, there is an urgent need to review the progress of such machine learning derived prediction models in the prediction of BBB permeability. In the current article, we have analyzed the recently developed prediction model for BBB permeability using machine learning.

Functional Biomolecule Delivery Systems and Bioengineering in Cartilage Regeneration.

Abstract: Osteoarthritis (OA) is a common degenerative disease which involves articular cartilage, and leads to total joint disability in the advanced stages. Due to its avascular and aneural nature, damaged cartilage cannot regenerate itself. Stem cell therapy and tissue engineering represent a promising route in OA therapy, in which cooperation of mesenchymal stem cells (MSCs) and three-dimensional (3D) scaffolds contribute to cartilage regeneration. However, this approach still presents some limits such as poor mechanical properties of the engineered cartilage. The natural dynamic environment of the tissue repair process involves a collaboration of several signals expressed in the biological system in response to injury. For this reason, tissue engineering involving exogenous "influencers" such as mechanostimulation and functional biomolecule delivery systems (BDS), represent a promising innovative approach to improve the regeneration process. BDS provide a controlled release of biomolecules able to interact between them and with the injured tissue. Nano-dimensional BDS is the future hope for the design of personalized scaffolds, able to overcome the delivery problems. MSC-derived extracellular vesicles (EVs) represent an attractive alternative to BDS, due to their innate targeting abilities, immunomodulatory potential and biocompatibility. Future advances in cartilage regeneration should focus on multidisciplinary strategies such as modular assembly strategies, EVs, nanotechnology, 3D biomaterials, BDS, mechanobiology aimed at constructing the functional scaffolds for actively targeted biomolecule delivery. The aim of this review is to run through the different approaches adopted for cartilage regeneration, with a special focus on biomaterials, BDS and EVs explored in terms of their delivery potential, healing capabilities and mechanical features.

Recent Development in the Fabrication of Collagen Scaffolds for Tissue Engineering Applications: A Review.

Abstract: Tissue engineering focuses on developing biological substitutes to restore, maintain or improve tissue functions. The three main components of its application are scaffold, cell and growthstimulating signals. Scaffolds composed of biomaterials mainly function as the structural support for ex vivo cells to attach and proliferate. They also provide physical, mechanical and biochemical cues for the differentiation of cells before transferring to the in vivo site. Collagen has been long used in various clinical applications, including drug delivery. The wide usage of collagen in the clinical field can be attributed to its abundance in nature, biocompatibility, low antigenicity and biodegradability. In addition, the high tensile strength and fibril-forming ability of collagen enable its fabrication into various forms, such as sheet/membrane, sponge, hydrogel, beads, nanofibre and nanoparticle, and as a coating material. The wide option of fabrication technology together with the excellent biological and physicochemical characteristics of collagen has stimulated the use of collagen scaffolds in various tissue engineering applications. This review describes the fabrication methods used to produce various forms of scaffolds used in tissue engineering applications.

Nanoparticles and Zeolites: Antibacterial Effects and their Mechanism against Pathogens.

Abstract: Nowadays, distribution and microorganism resistance against antimicrobial compounds have caused crucial food safety problems Hence, nanotechnology and zeolite are recognized as new approaches to manage this problem due to their inherent antimicrobial activity Different studies have confirmed antimicrobial effects of Nano particles (NPs) (metal and metal oxide) and zeolite, by using various techniques to determine antimicrobial mechanism This review includes an overview of research with the results of studies about antimicrobial mechanisms of nanoparticles and zeolite Many researches have shown that type, particle size and shape of NPs and zeolite are important factors showing antimicrobial effectiveness The use of NPs and zeolite as antimicrobial components especially in food technology and medical application can be considered as prominent strategies to overcome pathogenic microorganisms Nevertheless, further studies are required to minimize the possible toxicity of NPs in order to apply suitable alternatives for disinfectants and antibacterial agents in food applications

Effect of Pullulan on Physicochemical, Microbiological, and Sensory Quality of Yogurts

Abstract: Background Pullulan can partially or completely replace starch or fat, thanks to which it can be used for the production of dietetic food. It allows you to maintain the desired consistency, and increases the viscosity of the product. Objective Therefore, an attempt was made to produce yogurts with pullulan addition and determine the effect of its presence on the number of LAB, pH change, titratable acidity, and sensory quality of yogurts during storage at 4°C for 28 days. Methods The effect of addition of 0; 1.0 and 2.0 % w/v pullulan as a yogurt ingredient on the changes in pH, acidity, LAB number, and sensory quality of yogurt during storage at 4°C for 28 days was examined. Results Pullulan did not affect yogurt pH, but the addition of 2.0 % w/v pullulan increased the acidity of yogurt as compared to that of the control yogurt. A statistically significantly higher total number of Lactobacillus, by approximately 1 logarithmic cycle, was found in yogurts with pullulan than in the control yogurt on the 28th day of storage. The yogurt with 1.0% w/v pullulan addition showed better sensory characteristics than that with 2.0% pullulan w/v addition. Conclusion The conducted research proved that the presence of pullulan in the culture medium stimulates the growth of selected lactic acid bacteria and influences their fermentation capacity. The use of 1.0 % w/v pullulan during the production of yogurts allowed to obtain a sensorically acceptable product, it had a protective effect on the number of lactic acid bacteria during 28 days of refrigerated storage of yogurt.

New Rules on Patient's Safety and Professional Liability for the Italian Health Service.

Abstract: BACKGROUND The phenomenon of clinical negligence claims has rapidly spread to United States, Canada and Europe assuming the dimensions and the severity of a pandemia. Consequently, the issues related to medical malpractice need to be studied from a transnational perspective since they raise similar problems in different legal systems. METHODS Over the last two decades, medical liability has become a prominent issue in healthcare policy and a major concern for healthcare economics in Italy. The failures of the liability system and the high cost of healthcare have led to considerable legislative activity concerning medical malpractice liability, and a law was enacted in 2012 (Law no. 189/2012), known as the "Balduzzi Law". RESULTS The law tackles the mounting concern over litigation related to medical malpractice and calls for Italian physicians to follow guidelines. Briefly, the law provided for the decriminalisation of simple negligence of a physician on condition that he/she followed the guidelines and "good medical practice" while carrying out his/her duties, whilst the obligation for compensation, as defined by the Italian Civil Code, remained. Judges had to consider that the physician followed the provisions of the guidelines but nevertheless caused injury to the patient. CONCLUSION However, since the emission of the law, thorny questions remain which have attracted renewed interest and criticism both in the Italian courts and legal literature. Since then, several bills have been presented on the topic and these have been merged into a single text entitled "Regulations for healthcare and patient safety and for the professional responsibility of healthcare providers".

A Review on Targeting Nanoparticles for Breast Cancer.

Abstract: Chemotherapeutic agents have been used extensively in breast cancer remedy. However, most anticancer drugs cannot differentiate between cancer cells and normal cells, leading to toxic side effects. Also, the resulted drug resistance during chemotherapy reduces treatment efficacy. The development of targeted drug delivery offers great promise in breast cancer treatment both in clinical applications and in pharmaceutical research. Conjugation of nanocarriers with targeting ligands is an effective therapeutic strategy to treat cancer diseases. In this review, we focus on active targeting methods for breast cancer cells through the use of chemical ligands such as antibodies, peptides, aptamers, vitamins, hormones, and carbohydrates. Also, this review covers all information related to these targeting ligands, such as their subtypes, advantages, disadvantages, chemical modification methods with nanoparticles and recent published studies (from 2015 to present). We have discussed 28 different targeting methods utilized for targeted drug delivery to breast cancer cells with different nanocarriers delivering anticancer drugs to the tumors. These different targeting methods give researchers in the field of drug delivery all the information and techniques they need to develop modern drug delivery systems.

Cinnamate Hybrids: A Unique Family of Compounds with Multiple Biological Activities.

Abstract: Cinnamic acid derivatives are widely distributed in nature presenting a wide range of biological activities: antiseptic, stimulant, carminative and insecticidal activities. Hydroxy- cinnamic acids, especially caffeic, ferulic and chlorogenic, present various biological activities and they are synthesized in nature through the phenylpropanoid pathway. Additionally, the cinnamoyl moiety is present in various drugs such as a) Ozagrel, an imidazole π - substituted cinnamic acid acting as a thromboxane A2 synthase inhibitor, used therapeutically for treating acute ischemic stroke, b) Cinnarizine, Cinanserin and Tranilast, a series of antiallergic agents etc. During the last decade, scientists have focused on multifunctional molecules instead of a single molecule hitting one target. Multi-target drugs can be beneficial for the treatment of complex and multifunctional diseases. A variety of multi-target drugs contain the cinnamic acid moiety due to its biological importance and combination of biological activities e.g. antioxidant, antiiflammatory, anticancer, antituberculosis, antifungal, antimalarial, antiatherogenic, antimicrobial activities. Recently for the treatment of complex diseases hybrid drugs combining two pharmaceutical moieties in one molecule have been developed. These molecules are more medically effective than their individual components. In this review, a survey of cinnamate hybrids, that is molecules that combine the cinnamic acid moiety with at least a second pharmacophore with or without a linker, acting as "multi-target" agents, is given. The hybrids are listed in terms of their biological activity and applications as anti-Alzheimer, anticancer agents as well as for cardiovascular diseases, as antivirals, antimalarials etc.

Thymoquinone Shows the Diverse Therapeutic Actions by Modulating Multiple Cell Signaling Pathways: Single Drug for Multiple Targets.

Abstract: Thymoquinone (TQ), derived from the seeds of Nigella sativa, has lately been shown as a miracle drug because of its wide range of therapeutic effects against various diseases, including cancer, asthma, diabetes, colitis and infectious diseases. In the present review, we aimed to decipher the molecular mechanisms of therapeutic action of TQ by modulating the cell signaling pathways. Many in vivo and in vitro studies have demonstrated the therapeutic efficacy of TQ against a wide range of ailments. TQ possesses potent anti-inflammatory and immunomodulatory effects by specifically targeting the NF-kB, IL-1β and TNF-α signaling pathways. The anticancer activity of TQ has been primarily shown by altering the expression of signal transducers and activator transcription (STAT3), PTEN and p53 genes. TQ alleviates the hyperglycemia-associated complications, the hepatic or renal ailments through its potent antioxidant and anti-inflammatory properties. Interestingly, the liposome- or nanoparticle-based TQ formulations have shown greater effectiveness against various diseases in animal models. Thus, the understanding of the molecular mechanisms of TQ action may lead to the development of its therapeutic formulations to cure a wide variety of diseases.

Tuberculosis: Current Status, Diagnosis, Treatment and Development of Novel Vaccines.

Abstract: Tuberculosis (TB) is an infectious disease that mainly affects the lungs and spreads to other organs of the body through the haematogenous route. It is one of the ten major causes of mortality worldwide. India has the highest incidence of new- and multidrug-resistant (MDR) - TB cases in the world. Bacille Calmette-Guerin (BCG) is the vaccine commonly available against TB. BCG does offer some protection against serious forms of TB in childhood but its protective effect wanes with age. Many new innovative strategies are being trailed for the development of effective and potent vaccines like mucosal- and epitope-based vaccines, which may replace BCG or boost BCG responses. The use of nanotechnology for diagnosis and treatment of TB is also in the pipeline along with many other vaccines, which are under clinical trials. Further, in-silico models were developed for finding new drug targets and designing drugs against Mycobacterium tuberculosis (Mtb). These models offer the benefit of computational experiments which are easy, inexpensive and give quick results. This review will focus on the available treatments and new approaches to develop potent vaccines for the treatment of TB.

Medical Records Quality as Prevention Tool for Healthcare-Associated Infections (HAIs) Related Litigation: a Case Series.

Abstract: BACKGROUND Healthcare-associated infections are one of the most serious Public Health concern, as they prolong the length of hospitalization, reduce the quality of life, and increase morbidity and mortality. Despite they are not completely avoidable, the number of healthcare-associated infections related to negligence claims has risen over the last years, contributing to remarkable economic and reputation losses of Healthcare System. METHODS In this regard, several studies suggested a key role of medical records quality in determining medical care process, risk management and preventing liability. Clinical documentation should be able to demonstrate that clinicians met their duty of care and did not compromise patient's safety. RESULTS Therefore, it has a key role in assessing healthcare workers' liability in malpractice litigation. Our risk management experience has confirmed the role of medical records accuracy in preventing hospital liability and improving the quality of medical care. CONCLUSION In the presented healthcare-associated infections cases, evidence-based and guidelinesbased practice, as well as a complete/incomplete medical record, have shown to significantly affect the verdict of the judicial court and inclusion/exclusion of hospital liability in healthcare-associated infections related claims.

Effect of Vinca Alkaloids on the Expression Levels of microRNAs Targeting Apoptosis-related Genes in Breast Cancer Cell Lines.

Abstract: Background Treatment of cancer with natural chemotherapeutic agents induces apoptosis along with remarkable alterations in the expression of apoptosis-related genes. Deregulation of microRNA (miRNA) expression is implicated in several human malignancies. Vinca alkaloids compose a class of antimitotic drugs preventing cancer cells from dividing, leading to apoptosis. They are commonly used in clinical practice for breast cancer treatment. Objective The present study focused on the effects of vinca alkaloids (vincristine, vinblastine, and vinorelbine) on miRNA expression of treated breast cancer cells. Methods We investigated the effect of vincristine, vinblastine, and vinorelbine on the expression of oncogenic and tumor-suppressive miRNAs (miR-15a-5p, miR-16-5p, miR-21-5p, miR-25-3p, miR- 29b-3p, miR-125b-5p, miR-148a-3p, miR-214-3p, miR-221-3p, miR-222-3p, and miR-421), as well as on the expression of the apoptosis-related genes BAX, BCL2, TP53, and CDKN1B in BT-20 and SKBR- 3 breast adenocarcinoma cells. Results Treatment of BT-20 cells with vincristine, vinblastine, and/or vinorelbine resulted in upregulation of TP53 expression. However, no alterations in the mRNA levels of the pivotal BCL2 family members BAX and BCL2 were observed. On the other hand, treatment of SK-BR-3 cells with any of these vinca alkaloids led to an increase in the BAX/BCL2 mRNA ratio, implying the activation of the intrinsic apoptotic pathway. No concomitant alteration in TP53 expression was observed in treated SKBR- 3 cells. Regarding the miRNAs examined in this study, miR-222-3p expression exhibited the most remarkable modulations in both treated cell lines. Conclusion This study suggests the possible involvement of miR-222-3p expression in breast cancer cell apoptosis, triggered by vincristine, vinblastine, and vinorelbine.

Downregulation of TdT Expression through Splicing Modulation by Antisense Peptide Nucleic Acid (PNA).

Abstract: Background and objective Antisense oligonucleotides are able to modulate splicing patterns and offer therapeutic intervention for cancer and other diseases. Considering TdT potential as a target in cancer therapy, the present study aimed to investigate splicing alteration of TdT pre-mRNA in Molt-4 cells using peptide nucleic acid (PNA) octaarginine and cholic acid conjugates. Method We examined 16 mer PNAs targeting 5' and 3' junctions of intron 7 and addressed their mRNA splicing modulation effects using RT-PCR analysis. We also tested corresponding 2-base mismatch PNAs to confirm the sequence specificity. In addition, protien level of TdT, apoptosis induction and cell viability rate were analysed. Results PCR analysis showed that full match PNAs could modulate the splicing process, thereby producing a longer mRNA still including intron 7. PCR results also implied exon 7 skipping. In addition, reduced level of TdT protein in Molt-4 cells was observed. Downregulation of TdT level in PNA treated cells was accompanied by an increased rate of apoptosis and decreased the level of cell survival. Conclusion PNA-mediated splicing modulation can specifically downregulate TdT expression. TdT dowregulation results in apoptosis induction and reduced cell survival in Molt-4 cells. These observations could draw more attentions to develop PNA based strategies for TdT suppression and consequent apoptosis induction in acute lymphoblastic leukemia.

The Interaction of Zinc Oxide/Green Tea Extract Complex Nanoparticles and its Effect on Monosodium Glutamate Toxicity in Liver of Rats

Abstract: Background Zinc oxide nanoparticles (ZnO NPs) are increasingly utilized in both industrial and medical applications. Therefore, the study was aimed to investigate the effect of green nanoparticle complex (green tea extract/zinc oxide nanoparticles complex, GTE/ZnO NPs) on oxidative stress induced by monosodium glutamate (MSG) on the liver of rats. Methods Wistar male rats (n=64) weighing between 200-250 g were divided randomly into eight groups: control group was given physiological saline (1 mg/kg), two groups were treated with two different doses of MSG (MSG-LD, MSG-HD; 6 and 17.5 mg/Kg, respectively), GTE was given 1 mg/mL, 5th group was treated with ZnO NPs and 6th group was treated with GTE/ZnO NPs complex while, 7th and 8th groups were treated with MSG-LD + GTE/ZnO NPs complex and MSG-HD + GTE/ZnO NPs complex, respectively. All substances were given orally for 30 consecutive days. At the end of the study, the liver was homogenized for measurement of the oxidative stress status and anti-inflammatory biomarkers as well as histological and transmission alternations. Results Results showed that the antioxidant enzymes activity and glutathione level were significantly decreased in MSG groups than control in a dose-dependent manner. Conversely, the malondialdehyde and inflammatory cytokines levels were significantly increased in MSG groups than the control group. The liver indicated no evidence of alteration in oxidative status, anti-inflammatory and morphological parameters in GTE, ZnO NPs and GTE/ZnO NPs complex groups. Conclusion In conclusion, MSG at both doses caused oxidative stress and inflammation on liver after 28 days of exposure that supported histological analysis and transmission view of hepatic parenchyma. GTE/ZnO NPs act as partial hepato-protective against MSG.

Improving Bovine Bone Mechanical Characteristics for the Development of Xenohybrid Bone Grafts.

Abstract: Background The further functionalization of natural existing biomaterials is a very efficient method to introduce additional advanced characteristics on a unique structural composition and architecture. Objective As an example, different animal sources, if properly treated, can be used to develop bone xenograft active in hard tissues regeneration. In this sense, it is also important to consider that the selected process has to take into consideration the intrinsic variability of the base material itself and possibly being able to compensate for it. Methods In this work we characterize cancellous bovine bone treated by deposition of polymer and collagen and we show that the added components not only lead to a more resistant and more hydrophilic material, but also reduce the conventional correlation between apparent density and elastic modulus, which, in general, is a major source of uncertainty and risk in xenografts usage. Results Moreover, though intrinsically reinforcing the material, the deposition process leaves the specific open-porous structure, that allows cells proliferation and vessels ingrowth, basically unaltered. Conclusion The final material combines in a single piece and at the same time, mechanical resistance, homogeneous mechanical response and proper structural characteristics that allow further integration within the patient autochthonous tissues.

Valorization of Crude Glycerol, Residue Deriving from Biodiesel- Production Process, with the Use of Wild-type New Isolated Yarrowia lipolytica Strains: Production of Metabolites with Pharmaceutical and Biotechnological Interest.

Abstract: Background & objective Crude glycerol (Glol), used as substrate for screening eleven natural Yarrowia lipolytica strains in shake-flask experiments. Aim of this study was to assess the ability of the screened strains to produce biomass (dry cell weight; X), lipid (L), citric acid (Cit), mannitol (Man), arabitol (Ara) and erythritol (Ery), compounds presenting pharmaceutical and biotechnological interest, in glycerol-based nitrogen-limited media, in which initial glycerol concentration had been adjusted to 40 g/L. Methods Citric acid may find use in biomedical engineering (i.e. drug delivery, tissue engineering, bioimaging, orthopedics, medical device coating, wound dressings). Polyols are considered as compounds with non-cariogenic and less calorigenic properties as also with low insulin-mediated response. Microbial lipids containing polyunsaturated fatty acids (PUFA) are medically and dietetically important (selective pharmaceutical and anticancer properties, aid fetal brain development, the sight function of the eye, hormonal balance and the cardio-vascular system, prevent reasons leading to type-2 diabetes, present healing and anti-inflammatory effects). Results All strains presented satisfactory microbial growth (Xmax=5.34-6.26 g/L) and almost complete substrate uptake. The principal metabolic product was citric acid (Citmax=8.5-31.7 g/L). Production of cellular lipid reached the values of 0.33-0.84 g/L. Polyols were also synthesized as strain dependent compounds (Manmax=2.8-6.1 g/L, Aramax ~2.0 g/L, Erymax= 0.5-3.8 g/L). The selected Y. lipolytica strain ACA-DC 5029 presented satisfactory growth along with synthesis of citric acid and polyols, thus, was further grown on media presenting an increased concentration of Glol~75 g/L. Biomass, lipid and citric acid production presented significant enhancement (Xmax=11.80 g/L, Lmax=1.26 g/L, Citmax=30.8 g/L), but conversion yield of citric acid produced per glycerol consumed was decreased compared to screening trials. Erythritol secretion (Erymax=15.6 g/L) was highly favored, suggesting a shift of yeast metabolism from citric acid accumulation towards erythritol production. Maximum endopolysaccharides (IPS) concentration was 4.04 g/L with yield in dry weight 34.2 % w/w. Conclusion Y. lipolytica strain ACA-YC 5029 can be considered as a satisfactory candidate grown in high concentrations of crude glycerol to produce added-value compounds that interest pharmaceutical and biotechnology industries.

Recent Insights into Effective Nanomaterials and Biomacromolecules Conjugation in Advanced Drug Targeting.

Abstract: Targeted drug delivery, also known as smart drug delivery or active drug delivery, is a subcategory of nanomedicine. Using this strategy, the medication is delivered into the infected organs in the patient's body or to the targeted sites inside the cells. In order to improve therapeutic efficiency and pharmacokinetic characteristics of the active pharmaceutical agents, conjugation of biomacromolecules such as proteins, nucleic acids, monoclonal antibodies, aptamers, and nanoparticulate drug carriers, has been mostly recommended by scientists in the last decades. Several covalent conjugation pathways are used for biomacromolecules coupling with nanomaterials in nanomedicine including carbodiimides and "click" mediated reactions, thiol-mediated conjugation, and biotin-avidin interactions. However, choosing one or a combination of these methods with suitable coupling for application to advanced drug delivery is essential. This review focuses on new and high impacted published articles in the field of nanoparticles and biomacromolecules coupling studies, as well as their advantages and applications.

Tanshinone IIA Promotes Macrophage Cholesterol Efflux and Attenuates Atherosclerosis of apoE-/- Mice by Omentin-1/ABCA1 Pathway.

Abstract: Background Tanshinone IIA (Tan IIA) and Omentin-1 have a protective role in the cardiovascular system. However, if and how Tan IIA and Omentin-1 regulate cholesterol metabolism in macrophages has not been fully elucidated. Objective To investigate the possible mechanisms of Tan IIA and Omentin-1 on preventing macrophage cholesterol accumulation and atherosclerosis development. Methods The effect of Tan IIA on the protein and mRNA levels of Omentin-1 and ATP-binding cassette transporter A1 (ABCA1) in macrophages was examined by Western blot and qRT-PCR assay, respectively. Cholesterol efflux was assessed by liquid scintillation counting (LSC). Cellular lipid droplet was measured by Oil Red O staining, and intracellular lipid content was detected by high performance liquid chromatography (HPLC). In addition, the serum lipid profile of apoE-/- mice was measured by enzymatic method. The size of atherosclerotic lesion areas and content of lipids and collagen in the aortic of apoE-/- mice were examined by Sudan IV, Oil-red O, and Masson staining, respectively. Results Tan IIA up-regulated expression of Omentin-1 and ABCA1 in THP-1 macrophages, promoting ABCA1-mediated cholesterol efflux and consequently decreasing cellular lipid content. Consistently, Tan IIA increased reverse cholesterol transport in apoE-/- mice. Plasma levels of high-density lipoprotein cholesterol (HDL-C), ABCA1 expression and atherosclerotic plaque collagen content were increased while plasma levels of low-density lipoprotein cholesterol (LDL-C) and atherosclerotic plaque sizes were reduced in Tan IIA-treated apoE-/- mice. These beneficial effects were, however, essentially blocked by knockdown of Omentin-1. Conclusion Our results revealed that Tan IIA promotes cholesterol efflux and ameliorates lipid accumulation in macrophages most likely via the Omentin-1/ABCA1 pathway, reducing the development of aortic atherosclerosis.

Plant Phenolics and Lectins as Vaccine Adjuvants.

Abstract: Background The immune system is responsible for providing protection to the body against foreign substances. The immune system divides into two types of immune responses to study its mechanisms of protection: 1) Innate and 2) Adaptive. The innate immune response represents the first protective barrier of the organism that also works as a regulator of the adaptive immune response, if evaded the mechanisms of the innate immune response by the foreign substance the adaptive immune response takes action with the consequent antigen neutralization or elimination. The adaptive immune response objective is developing a specific humoral response that consists in the production of soluble proteins known as antibodies capable of specifically recognizing the foreign agent; such protective mechanism is induced artificially through an immunization or vaccination. Unfortunately, the immunogenicity of the antigens is an intrinsic characteristic of the same antigen dependent on several factors. Conclusion Vaccine adjuvants are chemical substances of very varied structure that seek to improve the immunogenicity of antigens. The main four types of adjuvants under investigation are the following: 1) Oil emulsions with an antigen in solution, 2) Pattern recognition receptors activating molecules, 3) Inflammatory stimulatory molecules or activators of the inflammasome complex, and 4) Cytokines. However, this paper addresses the biological plausibility of two phytochemical compounds as vaccine adjuvants: 5) Lectins, and 6) Plant phenolics whose characteristics, mechanisms of action and disadvantages are addressed. Finally, the immunological usefulness of these molecules is discussed through immunological data to estimate effects of plant phenolics and lectins as vaccine adjuvants, and current studies that have implanted these molecules as vaccine adjuvants, demonstrating the results of this immunization.

Phytosterols and Triterpenoids for Prevention and Treatment of Metabolic-related Liver Diseases and Hepatocellular Carcinoma.

Abstract: Background Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs. Review and conclusion Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.

Advanced Loss Eventuality Assessment and Technical Estimates: An Integrated Approach for Management of Healthcare-Associated Infections.

Abstract: BACKGROUND Healthcare Associated Infections (HAIs) represent a crucial issue in health and patient safety management due to the persistent nature, economic impact and possible preventability of the phenomenon. Compensation claims for damages resulting from HAI could provide insights that can improve the understanding of suboptimal steps in the therapeutic process, enable an estimate of costs related to infectious complications, and guide the development of planning tools for implementation of the quality of care. OBJECTIVE This paper analyzes all the HAI claims received at the Umberto I General Hospital of Rome across a five-year period with the aim of outlining a methodological approach to the litigation management and of characterizing the economic impact of infections on health facilities resources. METHODS All claims received during the study period have been classified according to the International Classification for Patient Safety (ICPS) system. Subsequently, claims related to Healthcare Associated Infections were evaluated through an innovative tool for determination of the risk of loss, the Advanced Loss Eventuality Assessment (ALEA) score. RESULTS The results obtained demonstrate the relevance of a correct management of HAI claims in the administration of a health care system. Specifically, the cases examined during the study highlighted the significant impact of infectious diseases of a nosocomial nature in terms of frequency and economic exposure. CONCLUSION The proposed methodological approach allows a productive analysis of the internal processes, providing fundamental data for the refinement of the preventive strategies and for the rationalization of the resources through the expenditure forecasts. Article Highlights Box: Healthcare-Associated Infections represent an essential element to consider in the management of health facilities. • Many studies highlight the economic burden of Healthcare-Associated Infections in health policies. • Litigation management represents a useful resource in the prevention of Healthcare Associated Infections. • Appropriate clinical risk management policies in the field of Healthcare-Associated Infections allow the implementation of preventive measures, the reduction of the incidence of the phenomenon and the quality of care. • The costs of Healthcare-Associated Infections can be limited through a systematic methodological approach based on Advanced Loss Eventuality Assessment and technical estimate of the value of each case. • The application of a standardized system would be desirable in any health facility despite the potential methodological, technical, behavioral and financial issues.