Microtiter well plate–based assays used to investigate antimicrobial activity of various nanoparticles.
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
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Swaroop",middleName:null,surname:"Meena",slug:"ram-swaroop-meena",fullName:"Ram Swaroop Meena"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"10878",leadTitle:null,title:"Bioethical Issues in Healthcare",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tThe issues in healthcare today are exploding. Every week we hear about both advances and setbacks in various technologies--CRISPR-Cas- 9, genetic testing, drug-resistant diseases, organ transplantation, brain death, etc. Bioethicists need to work collaboratively with one another globally not only to address these critical issues but also to offer some guidance on how to move forward in the best interests of humanity. Scientists, politicians, public policy advocates, pharmaceutical representatives, business executives are all searching for answers that will address the medical, ethical, and legal issues facing humanity. The role of the Bioethicist is to identify challenges, analyze issues, collaborate with colleagues to coordinate possible positions, and then help to implement changes.
\r\n\r\n\tThis book will challenge those in the medical, legal, and ethical fields to perform these tasks for the common good of humanity. This is an ambitious agenda but one that must be undertaken so that the public is made aware of these issues and what can be done to reach viable conclusions.
\r\n\t
The term antimicrobial was derived from the Greek words anti (against), micro (little), and bios (life), and it refers to all agents that act against microorganisms. Thus, antimicrobials include agents that act against bacteria (antibacterial), viruses (antiviral), fungi (antifungal), and protozoa (antiprotozoal). Among these, antibacterial agents are by far the most widely known and studied class of antimicrobials. Nowadays, the emergence of antimicrobial resistance (AMR) among the microbial pathogens greatly increases the threat generated by bacterial infections. Drug-resistant bacteria lead to poor clinical outcomes increasing health care costs and mortality. In the US, the estimated health care costs associated with the treatment of infectious diseases are annually more than 120 billion dollars, and further, treatment of infections caused by resistant pathogens costs 5 billion dollars per year [1]. According to the US Center for Disease Control and Prevention (CDC), more than two million antibiotic-resistant infections occur every year in the US and they lead to 23,000 deaths [2]. In the European Union, antibiotic-resistant infections are responsible for 25,000 deaths every year [3]. Both Gram-positive, especially methicillin-resistant
It is estimated that more than 70% of all pathogenic bacteria are resistant to at least one of the conventional antibiotics [11]. Antimicrobial resistance is acquired on both cellular and community levels [12]. Acquirement and dissemination of resistance genes is a process that occurs over time. Nevertheless, the evolution of bacterial resistance is substantially accelerated by the dispensable use of antibiotics [13]. Further dissemination of resistance genes between bacterial species has led to the emergence of multidrug-resistant (MDR) bacteria [14]. Community level of resistance is caused by biofilm formation [15]. However, when it comes to biofilms, the genetically transferable, conventional resistance mechanisms are not the leading cause of decreased antimicrobial susceptibility [7]. Bacterial biofilms are structured communities of bacteria embedded in a matrix of extracellular polymeric substances (EPS) that can be formed on variety of surfaces, such as tissues and medical devices [16]. Biofilm is a transient phenotype that makes even sensitive bacteria without known genetic basis for resistance to display remarkably reduced susceptibility to antimicrobials and host immune responses [17]. Many factors contribute to the antimicrobial tolerance of biofilms. First, biofilm matrix can restrict penetration of antibiotics and protects the cells from detrimental insults [18]. Secondly, biofilms comprise a heterogeneous population of cells that are in different physiological states due to decreasing oxygen and nutrient gradients existing between the surface and deeper layers of biofilms. For example, cells located in the deepest part of the biofilm tend to display a slower growth rate and, therefore, are less susceptible to antibiotics that are developed against dividing cells [19, 20]. Further, the non-dividing, dormant population of bacteria, referred also as persister cells, is in well-protected mode and highly tolerant antibiotics. These cells survive even from prolonged antibiotic treatment and serve as reservoirs for infections [21]. Consequently, biofilm bacteria can be up to 1000 times more tolerant to antimicrobial agents than planktonic cells of the same species [22].
\nDespite this, pharmaceutical companies have substantially declined investments in antimicrobial drug discovery during the past few decades [23]. Antimicrobial drug discovery is not economically attractive, and regulatory requirements have become very challenging [3, 24]. The need of novel bactericidal agents has increased due to the emergence of multi-drug resistant bacterial strains and biofilm-associated infections. Consequently, attention has been especially devoted to emerging nanoparticle-based materials in the field of antimicrobial therapies. In this chapter, the existing nanoparticles as antimicrobial means and the current
Antibacterial applications of nanotechnology are gaining importance to prevent the catastrophic consequences of antibiotic resistance. Nanotechnology can be implemented as preventives, diagnostics, drug carriers, and synergetics in the antibacterial therapies.
\nThe unique properties of nanomaterials compared to its bulk form make them favourable for antibacterial therapies. Many inorganic and organic nanomaterials represent inherent antibacterial properties that are not expressed in their bulk form. Fast and sensitive bacterial detection can be provided with nanoparticle-based approaches. Furthermore, nanoparticles offer discrete advantages as antibacterial drug delivery systems. They can be designed as targeted, environmentally responsive, combinatorial delivery systems [25]. Another approach of nanomaterials for the antibacterial therapy is as vaccine that contains nanoparticles as adjuvants or delivery vehicles, which provoke immune responses against bacterial infection. In the following parts in section 2.1 and 2.2, the existing nanotechnologies for the antibacterial delivery systems and inherently antibacterial nanoparticles will be discussed in detail.
\nThe existing disadvantages of conventional antibiotics can be solved to some extent by using nanomaterial-based antimicrobial delivery systems. In such approaches, the conventional antibiotics can be loaded into the nanoparticles through physical encapsulation, adsorption, or chemical conjugation. By this way, the pharmacokinetics and therapeutic index of the drug can ideally be improved compared to the free form of the drug. The aimed-for advantages are provided by the improved serum solubility, prolonged systemic circulation lifetime of the drug, targeted delivery of the drug to the site of infection, sustained and controlled release of the drug, and also combinatorial drug delivery to the site of interest that could be reached by virtue of the nanoscopic delivery system [26–28]. This rationale of nanotherapeutics in this case aimed to enhance the therapeutic effect and minimize the side effects of antibiotics, starts with the appropriate design of nanoparticles. In nanoparticles design, the particle size, surface properties, and the release profile of the therapeutic agent have vital impact on the success of the therapeutic approach. Various nanoparticles-based drug delivery systems have been designed and investigated for improving the efficacy of antibiotics of the administered drugs, the most common of which shall be outlined in the following.
\nLipid-based nanoparticles are widely used for the delivery of antibacterial agents. They can be designed as liposomes, solid lipid nanoparticles (SLN), and nanostructured lipid carriers (NLC). Liposomes are one of the most studied nanosystems for antimicrobial therapy in various diseases. Liposomes are spherical lipid vesicles with bilayered membrane structure, consisting of amphiphilic lipid molecules. Since their structure is similar to the bacterial cell membrane, efficacious interaction between liposomes and cells can be obtained. These interactions may create adsorption, endocytosis, lipid exchange, and fusion of the liposomes. Especially, the design of liposomes that cause fusion and is known as fusogenic is the most attractive one in the sense of efficiency. Fusogenic liposomes are able to destabilize the bacterial membrane and release their therapeutic content inside the cells [29, 30]. The structure of liposomes, where an aqueous cavity is surrounded by lipid membranes, empowers them to transport both lipophilic and hydrophilic drugs (in lipid bilayers and aqueous compartments, respectively) without chemical modification, protecting them from degradation [31]. SLNs are composed of a solid lipid core stabilized by surfactants and are moderately amorphous structures in which bilayers are not distinguished. They can provide long-term stability and better incorporation efficacy for hydrophobic drugs and can be easily scaled-up in production. NLCs were developed in order to overcome the limitations of SLNs regarding low-loading capacity for nonhydrophobic drugs and their stability issues. In the NLC structure, liquid lipids are used to stabilize the construct, which allows a biphasic drug release profile with initial burst release continued with sustained drug release. Liposomes have shown to be successful in combating resistant pathogens. Especially, their modified designs are used to improve the potency of formulations in bacterial resistance and clearance [32]. Additionally, researchers have confirmed the feasibility of SLN and NCL as drug carriers, however, their advantages over liposomes have not been confirmed with human data [33]. Most of the research on SLN and NCL as antimicrobial carriers are still in the preclinical stage.
\nTo date, a significant number of reports on the activity of antibiotic-conjugated polymeric nanoparticles against various infections, including those caused by drug-resistant pathogens, have been published [34]. Notably, high biocompatibility of these structures, additional to improved pharmacokinetic properties, supports the potential of these nanosystems as new tools to treat infections. Polymeric nanoparticles can be prepared from natural and synthetic polymers with the prerequisite of biocompatibility and biodegradability. In the polymeric antibacterial drug delivery systems, drug molecules can be incorporated in the internal part of the particles, on the surface of polymeric nanocarriers with covalent or non-covalent bonds, imprinted in the polymeric nanoparticles or encapsulated in the stimuli-responsive shell of polymeric nanoparticles [34]. The encapsulation route of the drug into the polymeric nanoparticle drug delivery system plays a key role in the nanocarriers’ pharmacokinetic profile. The action mechanism of the polymeric nanoparticles is defined by the physicochemical properties and the composition of the particles. Polymeric nanoparticles may interact with the bacterial cell wall via passive or active targeting. Passive targeting is based on particle size and the ability of particles to disturb the structure of bacterial membrane leading to pore formation in the membrane. For active targeting of polymeric nanoparticles, the surface of polymeric nanoparticles is usually functionalized with specific antibodies and aptamer bacteriophage proteins providing specific identification for the detection of pathogens and interaction between the particles and pathogens. The reported studies reveal that both the active and passive targeting strategies to deliver antimicrobial agents with polymeric nanoparticles improve their activities compared to their free forms [35–37].
\nDendrimers are highly branched macromolecules employed as antibacterial drug delivery systems. The unique properties of dendrimers, such as well-defined 3D structures, available functional groups, and their ability to mimic cell membranes, make them potential drug carriers. Both hydrophobic and hydrophilic drug molecules can be incorporated separately or at the same time into dendrimer structures. Lipophilic molecules can be incorporated inside the cavity of dendrimers, and hydrophilic agents can be covalently or physically attached to the surfaces of dendrimers. The antibacterial can be used in the building of dendrimer blocks, whereby the synthesized dendrimers themselves become potent antimicrobials. Dendrimers aid to improve the solubility, penetration, and controlled release of the drug molecules. Currently, the existing research in the design of dendrimers as antibacterial drug delivery systems also focuses on species-selective dendrimer biocide formulations. For instance, peptide, glycol, and glycopeptide dendrimer designs provide effective therapy for the bacterial infections.
\nAn inorganic nanomaterial, in contrast to the organic materials listed above, which has also shown promise for antibacterial therapies is mesoporous silica nanoparticles (MSNs). In the design of MSN-based drug delivery systems, their advantageous characteristics (biocompatibility, high surface area, tunable particle diameter, mesoporous structure, and ease of functionalization) have been exploited. The designs with targeted and sustained release mechanisms make them powerful candidates also for antibacterial therapies. In the use of MSNs as drug delivery vehicles for antibacterial therapeutics, their surface functionality along with the size and shape are crucial parameters to improve and optimize the efficacy [38]. Their surface functionalities can be modified to target both planktonic bacteria and biofilms [39]. In recent studies, the utility of MSN for efficient antibiotic delivery [36, 40, 41] and hybrid antibacterial materials preparation by incorporating antibacterial enzymes [42], peptides [43], metal ions/particles [44], and polymers (surface modifiers) [45] to MSNs has been reported.
\nFor rational and efficient utilization of these nanomaterial-based drug delivery systems, systematic investigation of pharmacokinetics and biodistribution should be carried out. The pharmacokinetics and biodistribution of nanoparticles are defined by their physicochemical properties [38]. Apart from their physicochemical properties, the administration routes and their elimination from the body need to be systematically evaluated. Hence, thorough evaluation of the current nanoparticle-based drug delivery systems in antibacterial therapies is important for their translation into the clinic. To date, four liposomal/lipid complex drug delivery systems for antibiotic delivery have been approved for use in human patients, including Abelcet, AmBisome, Amphotec, and Fungisome [46]. This should come as no surprise with regard that a liposomal formulation was the first nanodrug to hit the market in 1995 (Doxil®), and they have been studied since the early 1980s.
\nVarious types of inorganic and organic nanoparticles have been utilized as antibacterial agents. The inherent antibacterial properties of some metals and metal oxides have been known for centuries. An important advantage of antibacterial metal and metal oxide nanoparticles is that they have multiple modes of action, which is why microbes can scarcely develop resistance to them.
\nAmong the inorganic antibacterial particles, silver nanoparticles are the most intensively investigated ones and capable to kill both Gram-positive and Gram-negative bacteria, having even shown to be effective against drug-resistant species [46]. Besides silver nanoparticles, other metal nanomaterials have also been studied for antimicrobial treatment, including gold [47], copper [48, 49], tellurium [50, 51], and bismuth [52]. Moreover, many studies have revealed the antibacterial activity of metal oxide nanomaterials, such as zinc oxide (ZnO) [53], copper oxide (CuO) [54, 55], magnesium oxide (MgO), nitric oxide (NO) [56], titanium dioxide (TiO2) [57], aluminum oxide (Al2O3) [58], magnetic iron oxide (α-Fe2O3) [59], and cerium oxide (CeO2) [60] nanoparticles. The toxic mode of metal and metal oxide nanoparticles against bacterial cells has been associated with ROS generation and membrane disruption [61]. According to literature findings, the release of ions is designated as the driving force behind the antimicrobial properties of antibacterial nanoparticles.
\nCationic polymeric nanoparticles have been considered as promising organic antibacterial nanoparticles. They can be composed of natural or synthetic cationic polymers. The antibacterial polymeric nanoparticles kill microorganisms upon their contact with bacterial cells due to the strong interaction of their cationic surfaces with the bacterial cells [62]. The mechanisms of action have been proposed for how these cationic groups are able to disrupt the bacterial cell membrane, with some requiring hydrophobic chains of certain lengths to penetrate and burst the bacterial membrane. Moreover, different polymeric nanosized antibacterials with long-term antibacterial activity, chemically stable, and ability to bind to surfaces of interest have been reported. These include lipid nanoparticles, quaternary ammonium polyethyleneimine-incorporated polymeric nanoparticles [63, 64], chitosan [65], and self-assembled peptide nanoparticles [66]. In addition to the above-mentioned metallic and polymeric nanoparticles, carbon-based nanostructures have shown antibacterial effects. For instance, the antibacterial activity of fullerene [67] and carbon nanotubes [68, 69] (single-walled or multi-walled) derivatives have been observed. However, the antibacterial mechanism of carbon-based nanostructures is still under debate and has not received particular attention, possibly due to the difficulties of their dispersion in water, especially in case of the carbon nanotubes [70].
\nPromising approaches for the effective delivery of therapeutic compounds can be provided by the use of nanoparticles as drug carriers. Literature findings and clinical results have surely presented several clinical advantages of antimicrobial nanoparticles and their utilization as drug carrier systems. Antimicrobial nanoparticles are of great interest as they provide a number of benefits over free antimicrobial agents. In detail, nanocarriers can conquer the solubility and stability issues and reduce side effects [62]. With the use of nanocarriers in the delivery of drugs, combination drug therapy can be achieved by incorporating two or more drugs or different therapeutic modalities into the carrier matrix. The surface modifications can be carried out by conjugating targeting ligands on the nanocarriers that are not known by the immune system and specifically targeted to special microorganisms. Administration of antimicrobial agents using nanoparticles can increase the overall pharmacokinetics by progressing therapeutic index, extending drug circulation, and providing controlled drug release. Multiple mechanisms of action can be provided by the antibacterial nanoparticles, which prevent the development of antibacterial resistance by many pathogenic bacteria. Several routes of administration, including oral, nasal, parenteral, intraocular, and so on, can be employed with the nanotechnology-based antibacterial treatments.
\nThe significant advantages of nanomaterials as antimicrobial agents are their modularity in design, enabling a multimodal approach that makes it especially difficult for bacteria to develop resistance mechanisms against these. Namely, a nanotechnology-based antibacterial agent can be constructed out of several components that possess antimicrobial activities in themselves, such as, for instant, be composed of an antibacterial core material (e.g. metal or metal oxide) surrounded with an antibacterial polymeric shell or coating, in which antibiotic drugs could be incorporated [71]. The core material could further be “prickly,” which physically can destroy the bacterial cell wall by a “nano-piercing” process once the polymeric shell has been dissolved, leading to the disruption of bacterial integrity and lysis, as presented in a recent study by Wu et al. where zinc-doped copper oxide prickly nanoparticles exhibited high bacterial killing efficiency owing to the provided core particle nanostructure [72]. Furthermore, varying possibilities for combination therapy together with existing (commercial) antibiotics to reach synergistic effects are evident [14, 73, 74].
\nAlthough nanoparticle-based antibacterial treatments promise significant benefits and advances in addressing the key hurdles in treating infectious diseases, there are challenges in translating this exciting technology for clinical use. These include thoroughly evaluating the interactions of nanoparticles with cells, tissues, and organs, which accordingly recalibrates doses and identifies proper administration routes to obtain desired therapeutic effects. Hence, to provide a clinical translation of nanomaterials, standardized
Traditionally, antimicrobial research has focused on planktonic bacteria, and there is a variety of test methods available for evaluation of antimicrobial activity against planktonic cells [76]. The Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) are the major contributors to harmonized antimicrobial susceptibility testing (AST) providing uniform procedures for testing and analysis of antibacterial activity. CLSI standards clearly define the specific and essential requirements for materials, methods, and methodologies that need to be followed without any modifications because deviations from the approved procedures might affect the experimental outcome [77]. All the critical elements for the testing, such as the culture medium, inoculum density, and incubation conditions, are listed. Unlike the antibacterial assays, standardized methods for anti-biofilm studies are scarce. No standard methods have been approved by CLSI or EUCAST for evaluation of antimicrobial activity against biofilms. Altogether, five standards (ASTM E2196, ASTM E2647, ASTM E2562, ASTM E2799, and ASTM E2871) set by the American Society for Testing and Materials (ASTM) exist, and they all are applicable as such only for
Dilution methods are used to determine the MIC values of the antimicrobial agents. Moreover, they serve as reference methods for antimicrobial susceptibility testing. The minimum inhibitory concentration can be determined both on agar (agar dilution) and in broth (broth dilution). Standards for agar and broth dilution techniques used to assess the
Minimum inhibitory concentration (MIC) versus minimum bactericidal concentration (MBC).
When conducted on agar, a two-fold diluted series of the antimicrobial agent is incorporated into agar medium followed by inoculation of standardized suspension of the given organism onto the agar plate. Broth dilution can be performed in tubes (macrodilution, volume 2 ml) or in microtiter well plates (microdilution, volume ≤500 μl) containing a two-fold diluted series of antimicrobial agent prepared in the liquid growth medium that is inoculated with a standard inoculum of bacteria followed by a defined incubation period under particular conditions. After the incubation, the outcome is read based on turbidity or growth zones, and the MIC is defined. The MIC value can also be utilized to distinguish between bactericidal and bacteriostatic activities. Alternatively, when using microdilution, the MIC can be determined spectrophotometrically according to the EUCAST protocol [81]. In addition to CLSI and EUCAST standards, ISO-20776-1 standard proposes acceptable performance criteria for microdilution method. After broth dilutions, the MBC can be determined by sub-culturing the samples from tubes or wells and plating on agar to determine the number of cells (CFU/ml) after incubation for 24 h. Then, MBC is defined as the lowest concentration at which 99.9% of the final inoculum is killed (Figure 1). The main advantage of the dilution method is a generation of quantitative data, the MIC value. Moreover, the assay is overall reproducible, and small amounts of antimicrobials are needed when the microdilution method is utilized. By contrast, large amounts of antimicrobial agents are needed in macrodilution testing. The main disadvantage of the method is several steps in sample preparation, which in turn, increases the possibility of errors.
\nStandards for antimicrobial disk susceptibility test are proposed in the document M02-A12 by the CLSI. Specifications for the agar (type, depth), concentration range of the test antimicrobial, concentration of the microorganism and incubation conditions (time, temperature and atmosphere) are included. Also, interpretation of the results, quality control procedures, and limitations of the methods when used for susceptibility testing of aerobically growing bacteria are described. Agar disk diffusion method is routinely applied to the
Disk diffusion test and antimicrobial gradient diffusion method. On the left, agar plate showing zone of inhibition by different antimicrobials of diameter of zones of inhibition refers to the susceptibility of a microorganism.
The antimicrobial gradient diffusion method is based on the establishment of an antimicrobial concentration gradient in the agar medium to measure the antimicrobial susceptibility. Thin plastic test strips marked with concentration scale and impregnated with antibiotic concentration gradient are placed on agar plates that have been inoculated with a standardized inoculum (Figure 2). After incubation overnight, the experimental outcome is read, and the MIC can be determined by the intersection of the lowest part of the ellipse-shaped growth inhibition area with the test strip. E-Test is the commercially available test for this purpose.
\nTime-kill assay is complementary to MIC and MBC determinations. It provides information on the dynamic interaction between the antimicrobial and microorganism, thus revealing whether the antimicrobial effect is time or concentration dependent. Such activities can be investigated utilizing the standard protocol M26-A by CLSI and ASTM2315. These protocols are frequently modified. Time-kill assay is usually conducted at a concentration twice or four times the MIC. Standardized inoculum is added to a nutrient broth containing the antimicrobial at various concentrations. A sample is taken from each concentration at the inoculation time and after selected time points. Samples are serially diluted and viable plate counts are performed. The kill curves are constructed by plotting the log CFU against time. A 3-log reduction in cell counts corresponding the killing of 99.9% is considered as significant antimicrobial activity [83]. Alternatively, measurement of luminescence can be utilized to determine the time-kill relationship. Luminescence is detected by the ATP assay, in which adenosine triphosphate (ATP), an indicator for bacterial viability is quantified, and the number of viable cells is determined based on the amount of ATP. The assay uses luciferase reaction, in which luciferin is converted to oxyluciferin in the presence of molecular oxygen and ATP, and generates light by luminescence. Luminescent signal is proportional to the number of viable cells [84].
\nSince conventional susceptibility testing methods are not applicable for biofilms, and the MIC values do not provide a valid estimation of the antibiotic concentration needed to treat biofilm-related infections, the minimum biofilm inhibitory concentration (MBIC) has been determined instead. The MBIC determines the susceptibility of bacteria when the biofilm is forming and refers to the lowest concentration of an antimicrobial, in which no visible growth occurs after exposure to antimicrobial after the incubation period, and it can be recorded by optical reading [85]. Based upon the viable plate counts, the MBIC is defined as the lowest antimicrobial concentration in which there is no time-dependent increase in the mean number of viable cells between two exposure times [86]. Moreover, the Calgary Biofilm Device (CBD) can be used for determination of MBIC, as well as the minimum biofilm eradication concentration (MBEC), which is defined as the lowest concentration of an antimicrobial required to eradicate the established biofilms [87] along with susceptibility of planktonic bacteria (MIC) [22]. The commercially available CBD consists of 96 pegs mounted on the lid of a 96-microtiter well plate. Biofilms are first formed on the pegs for a defined time period. After the incubation period, the lid is transferred to another 96-well plate containing antimicrobials in fresh culture media at various concentrations. The MBEC is defined as the concentration of antimicrobial in which no visible growth can be detected [88]. ASTM 2799 standard describes the operational parameters required to grow, treat, sample, and analyze
Several assays with distinct endpoints are essential for the determination of the antimicrobial activity against biofilms. These assays rely on quantification of (i) viable cells in the biofilm, (ii) total biomass and (iii) biofilm matrix. An ideal anti-biofilm agent would target biofilm viability, biomass, and the matrix. Most of the assays are based on various staining methods. Several models have been proposed for evaluation of antimicrobial activity on biofilms. Depending on the flow of nutrients and bypass the waste products, biofilm models can be classified as closed and open systems [89]. Microtiter well plate-based assays are the most commonly used, while the Calgary biofilm device, substratum suspending reactors, and the flow cell system are the most widely used biofilm models for
Crystal violet (Hexamethyl pararosaniline chloride, CV) assay is not only one of the oldest but also most widely used staining methods applied to biofilm quantification [90, 91]. Crystal violet is an inexpensive and basic dye that is used to measure the effects on total biomass of biofilms. Crystal violet binds indifferently to both negatively charged bacteria and polysaccharides present in the EPS. After staining, adsorbed dye is eluted in a solvent, such as acetic acid or ethanol. The amount of the dye solubilized by the solvent is measured spectrophotometrically, and it is directly proportional to biofilm biomass [92, 93]. Disadvantages of the method are shortcomings in its dynamic range, laboriousness, and low reproducibility [92]. Experimental conditions, bacterial species, concentration, and nature of the solvent used, as well as incubation time are crucial steps that affect the experimental outcome. Furthermore, the assay does not sort out living or dead cells or biofilm matrix, thus not providing any information on the number of living bacterial cells [93] and, more importantly, imprecise information on the antimicrobial activity. However, the method can be used for both Gram-negative and Gram-positive bacteria and fungi, but the optimal assay conditions, such as temperature, incubation time, and solvent, vary between species [94, 95].
\nResazurin, also known as alamar blue (7-hydroxy-3H-phenoxazin-3-one-10-oxide), is a non-invasive, non-fluorescent dye, which is reduced to resorufin, a pink, fluorescent dye as a result of metabolically active cells and bacterial viability. Resorufin is detected spectrophotometrically to determine the viable cells [96]. Resazurin staining assay can be used to assess the antimicrobial activity based on the effects on viability of various microorganisms grown in suspensions or as biofilms [97]. However, time of resazurin reduction is species and strain specific. Consequently, the experimental conditions, such as incubation time and resazurin concentration, need to be optimized to obtain reproducible data [93, 98].
\nThe assay is used to measure nonspecific esterase activity of viable microbial cells that converts colorless, nonfluorescent FDA to fluorescein, which is a green fluorescent compound that can be quantified fluorometrically [88]. The assay is not widely used because the dye rapidly leaks from the cells and is unstable. Moreover, hydrolysis of FDA to fluorescein in the absence of live cells and quenching of fluorescence by assay solutions may also occur under certain conditions, thus making the reliability of the assay questionable. However, the assay enables biofilm quantification without removing biofilm from the place where it has been formed, allowing the quantification of entire biofilm [84, 99].
\nBiofilm viability can be assessed using tetrazolium salt reduction assay, in which tetrazolium salts, such as MTT (3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide), XTT (2,3-bis-[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide), and MTS (3-[4, 5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium), are reduced to formazan dyes. The color change can be quantified spectrophotometrically. The amount of formazan dye produced is proportional to the number of viable cells. However, the amount of reductase enzyme produced by cells is dependent on metabolic activity [100, 101]. In other words, cells that are metabolically less active when encased in a biofilm produce also reduced amount of reductase enzyme that can lead to identification of artificially low quantities of cells when viable cells are detected using this assay. Moreover, high densities of bacteria may produce the maximum amount of formazan product leading to optical densities comparable with even higher cell densities [102].
\nViable plate counts (colony forming unit counting) are used to assess the biofilm viability based on cell counting. The assay can be used to evaluate the efficacy of antimicrobials to prevent biofilm formation or eradicate pre-formed biofilms, respectively [103]. Depending on the assay mode, bacteria and antimicrobials are added simultaneously to the microtiter well plates or biofilms are first allowed to form followed by the exposure to antimicrobial. After an incubation period, biofilms are dislodged and disaggregated. The resulting suspensions are carefully homogenized, for example, by vortexing or sonication [93]. Subsequently, suspensions are serially diluted and plated or spread on agar. Colony forming units (CFUs) per surface area or volume are counted after an incubation period. The experimental outcome can be evaluated as reduction in CFUs compared to untreated control biofilms. The method gives accurate information on bacterial viability [94]. However, it is regarded as a time-consuming and laborious methodology because of serial dilutions and plating. Additionally, special attention needs to be addressed to the detachment and disaggregation steps to avoid false negative/positive results. The complete recovery and disaggregation of biofilm need to be ensured by applying methods that do not affect viability of the biofilm cells [93, 104].
\nWith respect to the evaluation of antimicrobial activity of nanoparticles, only one specific standard is set by the International Organization for Standardization (ISO), and it is intended for determination of the antimicrobial potency of silver nanoparticles against
Both standardized and modified microdilution and macrodilution methods have been applied to the determination of MIC and MBC values to evaluate the antimicrobial susceptibility of se-veral microorganisms to nanoparticles [76, 109, 110–116]. Additionally, resazurin staining assay has been employed to determine the MIC. The MIC was recorded as the lowest concentration at which color change from blue to pink occurred [117]. Even though standardized antimicrobial susceptibility testing protocols can be followed, no standards describing the synthesis of nanoparticles exist. Differences in the synthesis methodology are known to impact the particle size and chemical composition of the nanoparticles, which, in turn, can further affect the antimicrobial activity and cause variability in the experimental outcome [1, 118]. Hence, the impact of such factors has to be taken into consideration when results between studies are compared.
\nDiffusion methods can be applied alongside dilution assays to confirm the antimicrobial susceptibility of microorganisms [108, 119, 120]. Agar disk diffusion tests performed both according to the standardized protocols and with modifications are frequently used for susceptibility assessment and evaluation of antimicrobial activity of nanoparticles [109, 121–124]. Paper disc method has been employed as an alternative to standardized single disk method [112]. Further, agar well diffusion assays have been successfully utilized for the evaluation of antimicrobial effects of nanoparticles [120, 125, 126].
\nAntimicrobial effects can also be determined by reading the optical density [125]. Even though measurement of optical density is a straightforward method, it is not the most suitable for measuring the activity of nanoparticles because nanoparticles as such can also interfere with the optical density [46, 127]. Viable plate counts have been frequently performed according to the various protocols to assess the antimicrobial efficacy of nanoparticles against both planktonic and biofilm-growing bacteria [109, 128, 110–112, 116]. Samples can either be spread or pipetted on agar plates followed by overnight incubation and determination of the number of CFUs [116, 111, 113–115]. Especially, when quantifying the biofilm bacteria, efficient disaggregation of samples is of great importance to avoid false positive results.
\nCrystal violet staining is the most widely applied staining assay to investigate the antimicrobial activity of the various nanoparticles against biofilm-growing bacteria [129, 130, 121, 116, 131, 132]. By combining assays that quantify different features of biofilms, more relevant information on the activity of nanoparticles can be obtained. In that context, effects of nanoparticles on biofilm inhibition have been studied using viable plate counts and crystal violet staining in parallel [133, 134]. Additionally, LIVE/DEAD and crystal violet staining has been combined for the same purpose [133, 134]. Crystal violet staining has been also used together with resazurin staining assay to assess the impact of nanoparticles on total biomass, including the matrix components and biofilm viability, respectively [135]. Further, crystal violet along with phenol has been applied to quantify the effects on biomass and EPS [136]. Antimicrobial agents displaying bactericidal effects have usually an impact on both viability and biomass, while antimicrobials acting like detergents affect only the biomass [137]. Further, to distinguish between bactericidal and bacteriostatic activities, LIVE and DEAD staining of bacterial biofilms can be conducted using a combination of fluorescein diacetate (FDA) and propidium iodide (PI) dyes or by commercially available LIVE/DEAD kit containing propidium iodide (PI) and SYTO9 fluorescent dyes [136, 138]. Commonly used microtiter well plate-based assays are summarized in Table 1.
\nAssays | \nEndpoint | \nRead-out | \nPlanktonic bacteria | \nBiofilm | \nRef. |
---|---|---|---|---|---|
Measurement of optical density | \nGrowth inhibition, MIC | \nAbsorbance | \nX | \nX | \n[119, 125] |
Resazurin staining assay | \nViability, MIC | \nFluorescence | \nX | \nX | \n[117, 136] |
Tetrazolium salt reduction assay (MTT, XTT, MTS) | \nViability | \nFluorescence | \nX | \nX | \n[111, 132, 142, 143] |
Crystal violet staining assay | \nBiofilm biomass, MBIC | \nAbsorbance | \n– | \nX | \n[132] |
Fluorescein diacetate (FDA) assay | \nViability | \nFluorescence | \nX | \nX | \n[143, 144] |
Microtiter well plate–based assays used to investigate antimicrobial activity of various nanoparticles.
In order to gain information on the mechanistic action of nanoparticles, antimicrobial assays can be conducted in two modes, prior to and post biofilm formation. In the pre-exposure mode, nanoparticles and bacteria are simultaneously added, whereas in post-exposure mode, biofilms are first allowed to form, followed by the exposure to nanoparticles. Crystal violet staining has been used to evaluate the impact of nanoparticles on biofilm formation and eradication, respectively [139, 140, 127, 141], and viable plate counts have been utilized in the investigation of the antimicrobial efficacy of nanoparticles in the prevention of biofilm formation and eradication of pre-formed biofilms [111, 112].
\nThere is a strong demand to develop novel antimicrobial materials, and the emergence of nano-technology is creating a variety of options in this respect. Numerous nanoparticles exhibit antibacterial activity against several bacterial species. Today, nanomaterials are a promising platform to control bacterial infections in a broad range of applications. However, the absence of standardizations in testing methods leads to inconsistency in results. The foremost requirement of the assays applied to the evaluation of antimicrobial activity is reproducibility. Antimicrobial activity should be tested against various microorganisms, preferably against representatives of both Gram-negative and Gram-positive species. Moreover, a combination of several assays is preferred to confirm the activity. Several standardized methodologies exist for testing the antibacterial activity of conventional agents against planktonic bacteria. These methods are not applicable for biofilms, and further, they do not allow the prediction of the
Japan’s declining birthrate and aging population are becoming increasingly serious issues. Indeed, the shrinkage of the working population continues unabated [1]. The Ministry of Health, Labour and Welfare [2] reported a future shortage of anywhere from 60,000 to 270,000 nurses in 2025. This shortage might make it difficult to provide sufficient patient care, especially for older adults who need long-term care [3].
\nBeyond this, as of early November 2020, coronavirus disease 2019 (COVID-19) became a major threat to global public health. Globally, the number of patients with COVID-19 is approximately 52 million [4]. Notably, COVID-19 is caused by the SARS-CoV-2 virus, which spreads among people, mainly when an infected person is in close contact with others [5]. Significantly, many COVID-19 clusters have been reported in clinical settings, including long-term facilities.
\nIn Japan, the Ministry of Health, Labor and Welfare [6] recommends that people employ basic strategies to prevent the spread of infectious diseases, including COVID-19. These include hand washing, proper cough etiquette, wearing a mask, and avoiding group gatherings in poorly ventilated spaces. Although potential vaccines are under development, it remains necessary to make lifestyle changes that extend to human interaction, recognizing the possibility that new infectious diseases may gain prevalence in the future.
\nRobots are attracting attention as a countermeasure for such serious situations. Of the various forms of human interaction, communication with others is important as it helps improve the quality of life (QOL) and sociality of older adults and patients with dementia. Accordingly, healthcare communication robots (HCRs) have the potential to support the needs of patient dialog as an alternative to healthcare providers, thereby preventing infections and addressing staff shortage situations.
\nUsing HCRs for patient care is a collaborative process that requires not only engineers but also healthcare providers, such as nurses, who have a mandate to protect patient rights and maintain safety. Indeed, it is necessary to consider potential issues that may arise from this development. Thus, this paper discusses expectations and ethical dilemmas in relation to HCRs from the perspective of nurses.
\nCommunication with others is important because it is satisfying and fosters a sense of connection. Especially, conversation with others achieves mutual understanding through shared experiences and feelings. However, in Japan, community relationship networks are becoming degraded by the progressively aging society and the trend of nuclear families, which have become serious local problems. Particularly among older adults who have lived alone or had physical functional disorder, social activity and conversation with others tend to decrease.
\nNotably, long-term facilities have seen a rise in dementia patients, and the behavioral and psychological symptoms of dementia (BPSD) may cause irritability and restlessness among patients [7]. When nurses care for older adults and patients with dementia, it is important that they take time to listen to them to provide appropriate, high-quality care in a way that suits the patient [8].
\nHowever, the staffing of nurses in long-term facilities and nursing homes for older adults is lower than in acute care hospitals [9]. Due to this shortage of healthcare providers, it might be burdensome for staff to take sufficient time for dialog with older adults [10, 11].
\nClearly, the quality of care for older adults may be suffering because of labor shortages, especially in long-term care settings. This quality of care may be expected to improve when healthcare workers have HCRs as partners. Moreover, HCRs may also provide patients with the opportunity to talk, even in situations where an infectious disease such as COVID-19 is concerned.
\nThe Japanese government has already supported the introduction of HCRs to facilities for the elderly (such as nursing homes) as well as healthcare facilities [12] and hospitals [13]. While HCRs are still being developed and introduced in certain facilities, there are no HCRs specialized for older adults and patients with dementia [14]. Hence, it is necessary to improve the application that enables dialog with members of these demographics and to enhance the safety and features of the robots [15].
\nThe development of HCRs capable of dialog and therapeutic communication is a future goal. Here, “dialog” is not just a conversation, but the recognition and respect for each other’s values and establishing a relationship of trust.
\nThis speaks to the larger need for the development of HCRs that can interact with the elderly, increase conversation opportunities for them, satisfy their desire for approval, maintain their sociality and sense of purpose, and improve their QOL. Furthermore, by collecting information from the cloud database of these robots, healthcare providers may be able to determine whether urgent or immediate care is necessary, allowing them to listen to the patients more intensely.
\nThe acute care field is marked by the responsibility to care for patients suffering from threatening infectious diseases such as COVID-19. The risk of infection is very high for medical staff [16], who must find a way to take care of patients within the boundaries of time constraints, while also striving to prevent getting infected. Unsurprisingly, most medical staff find it difficult to take enough time to listen to patients’ feelings, particularly when they are fighting the fear of COVID-19 infection [17, 18]. Thus, patients with COVID-19 may lose the opportunity to express themselves because they have limited time to talk to their medical staff and limited visits with family and friends.
\nTraditional (human) nurses are accustomed to listening to a patient’s voice. However, in an emergency, HCRs may be able to note a patient’s anxiety and complaints and provide them with appropriate care in response. If the HCR can be linked with information from thermography and electronic medical records, it will also be possible to observe simple physical conditions among patients. Thus, the HCR may also serve as an alternative to care supporters for people who have been in shelters for long periods due to large earthquakes, etc.
\nAs recent years have seen the rapid development of robots and artificial intelligence (AI), ethical codes and guidelines have been issued by related academic societies largely in the engineering field [19, 20]. Ethical studies concerning AI and robots are also underway. UK-RAS network describes that the ethical concerns raised by robotics and autonomous systems (RAS) depend on their capabilities and domain of usage of Robotics, there are ethical issues such as Bias, Deception, Employment, Opacity, Safety, Oversight, and Privacy [21]. Of course, ethics are crucial to healthcare because healthcare workers must recognize dilemmas: using good judgment to make decisions informed by their values but also governed by the law.
\nA nurse, a type of healthcare provider, is a person who engages in providing care to persons with injuries and/or illnesses, and/or postpartum women, and/or assists in the provision of medical treatment under the license of the Ministry of Health, Labour and Welfare (Article 5 of the Act on Public Health Nurses, Midwives, and Nurses). Based on the Nursing Code of Ethics of the International Council of Nurses (ICN) [22], and the Japanese Nursing Association (JNA) [23], nurses are required to provide care while respecting human life, dignity, and rights according to the law.
\nHowever, just as patients are unique and vary in age and condition, nurses have their own cultural, religious, moral, and professional values. Thus, there are often conflicting values, disagreements, and ethical conflicts in nursing settings.
\nEthical dilemmas in nursing settings are far-reaching. From time to time, nurses make ethical decisions by taking a variety of information into account to determine the best choice for the patient. Nurses can take appropriate actions when faced with an ethical dilemma by understanding and applying ethical guidelines such as the American Nurses Association’s Code of Ethics [24], the ICN Code of Ethics for Nurses [22], and the JNA Code of Ethics [23].
\nIn Japan, decisions about ethical dilemmas are informed by the six principles of ethics (Beneficence, Non-maleficence, Autonomy, Veracity, Justice, and Fidelity) (Table 1) [25, 26]. These principles are familiar to nurses. Even after making ethical decisions, nurses reflect on those decisions and strive to increase their ethical sensitivity daily.
\nWhen HCRs are introduced to long-term facilities and hospitals, different ethical dilemmas might occur.
\nIf the HCRs, in the near future, can use dialog to make autonomous decisions regarding patients, and serve to replace a human nurse, relevant ethical discussions must precede this change. For instance, one would logically consider the questions of whether HCRs can have a sense of ethics like human nurses, and whether the former can make ethical decisions in the midst of ethical conflicts within nursing settings.
\nOur research currently uses the humanoid robot, Pepper (SoftBank Robotics Corp.) [28], in a long-term facility to develop an application for healthcare robots that can communicate with older adults based on principles of care. It also seeks to evaluate a program that can be run in a clinical context (developed by the Xing Company). However, in the implementation of this strategy, the communication function of Pepper’s application has proven deficient.
\nIt is important to understand the present HCRs’ competency as well as other factors that may enhance this application, making it suitable for use among older adults. To explore HCR-related issues in healthcare settings, we interviewed five healthcare providers (nurses, caregivers, and physiotherapists) at three facilities about current usage issues with Pepper. From these results, I examined ethical dilemmas from the nurse’s perspective concerning the development and introduction of HCRs that can interact with older adults. This analysis was based on four issues: burden on staff and insufficient support system, inadequate communication function, leakage of personal information and violation of right to privacy, and guaranteeing the safety and security of HCRs.
\nThe complexity of the robot’s operation, the ambiguity of the HCR support system, and the burden of preparation and cleanup of HCRs are some of the issues faced by the staff while working with HCRs. Pepper weighs approximately 30 kg (around 66 lbs.), stands 120 cm (approximately 47 inches) tall [28], and requires extra staff to prepare it for use and clean it. In addition, there are other issues related to its operational complexity and unclear support system (e.g., where to check when the robot freezes). These issues sometimes occur due to the application’s up-data. In many cases, a specific healthcare staff member accustomed to handling such equipment is in charge of making the introduction, placing additional burden on that staff member. At such times, staff support is required to facilitate interactions and conversations between humans and robots [29].
\nWhen HCRs are used in healthcare settings, it is important to avoid increasing the human burden and preventing the traditional nurse from being deprived of time to care for the patient. This is related to the ethical principle of justice. Nurses must decide the just or fair allocation of healthcare resources [25, 26]. With the introduction of robots, the principles of beneficence (providing good nursing to all patients), non-maleficence (avoiding harm caused from using HCRs), and justice (providing proper and fair nursing to all patients) should not come at the cost of staff conflict. Undue burden placed upon nurses, such as the aforementioned HCR handling and use requirements, may incline nurses to put an end to the introduction of robots in healthcare settings as they cannot provide adequate care and ensure the patient’s safety. Indeed, convenience (which includes appropriate sizing) and generous support are key for HCR use. It is also necessary to have functions that can be used by medical professionals who are not well versed in robotics and/or engineering.
\nA human nurse naturally changes the manner (speed, volume, delivery, tone) and content of their speech depending on the patient, the nurse’s personal experience, and various other factors. Conversely, the current HCRs cannot change how they talk to patients. Thus, older adults and patients with dementia may give up the conversation, feel discouraged, and/or experience negative emotions because the timing of HCRs’ utterances and the content of the response may be insufficient and the conversations may be unengaging. This has implications for the ethical principle of non-maleficence.
\nThe challenge here is to set the goals for the HCRs’ dialog function to include the examination of word choice (including the determination of inappropriate words). Clearly, the dialog function will rapidly improve in the future. However, traditional nurses are currently better placed to provide care to patients based on nursing ethics and while exercising professional responsibility.
\nEven during the clinical trials for HCR development, nurses must protect patients’ rights. Patients should not be harmed; they should not experience negative feelings or feel discouraged by HCRs (the principle of non-maleficence). Nurses should ensure that patients receive the best care from HCRs and human nurses (the principle of beneficence). Furthermore, it is particularly important to solicit patients’ opinions concerning their willingness or desire to interact with the HCRs (principle of autonomy); they should be permitted the personal liberty to determine their own decisions on whether to receive care from HCRs [25, 26]. Nurses give top priority to the safety of the subject and thereby play an advocacy role. Therefore, if patient rights and their ethical principles are violated, nurses may need to halt the promotion of robot development.
\nThe third issue involves the collection of patient information stored in the cloud server or body of HCRs, and how this information is managed. Indeed, HCRs need to store information to a cloud server for improved functioning. A cloud server allows for information input from various sources, along with simultaneous compilation and analysis [30]. This is significant, as there is a lot of information in the dialog between patients and HCRs.
\nThe guidelines regarding AI and robots have included effective policies such as protection and promotion of human rights, safety, and privacy [19, 20, 31]. Nevertheless, in the near future, when HCRs use the cloud server to store big data collected from their patients, an information leakage accident may occur [32]. This issue could, for instance, arise due to some malfunction during the development stage.
\nThe right to privacy does not have a legal basis in Japan. However, the right to privacy is recognized under the law of precedent as part of the pursuit of happiness referred to in Article 13 of the Constitution. In addition, personal information, in principle, cannot be provided to a third party (Article 23), except in cases where the allowance is based on laws and regulations (Article 23–1).
\nNurses also have a duty to protect patients’ privacy as a component of patient care (Article 42–2 of the Act on Public Health Nurses, Midwives, and Nurses). As stated in the code of nurse ethics, “Nurses should honor confidentiality and strive for the protection of personal information, while using appropriate discretion in the sharing of this information” [32]. Hence, it is important to safeguard against personal information leakage from HCRs or iCloud servers (the principles of fidelity, and non-maleficence).
\nThe fourth issue is the need to ensure the safety of interactive robots. In healthcare settings, there are hazardous things that might result in daily medical accidents or incidents. A medical accident involving a nurse may happen while providing nursing care or while assisting medical treatment that involves medical interventions [33]. Healthcare institutions continue to improve their policies and framework to secure organization-wide safety [34]. Nurses consistently make patient safety a top priority (the principles of non-maleficence: avoiding harm caused by HCRs, and beneficence: providing better nursing to all patients). This consideration entails predicting potentially dangerous patient behavior and performing other forms of safety and risk management (the principle of non-maleficence).
\nPresently, there are no reported medical accidents due to the use of HCRs. Unless there is a guarantee that accidents due to patient falls or contact will not occur, and that the safety of nurses and medical staff will be ensured, the introduction of HCRs should not be viewed passively.
\nFor instance, we must consider whether HCRs that can interact with older adults and patients with dementia need a self-propelled function and/or humanoid figures, and whether these things would enhance patient safety. Moreover, different cases must be studied along with the safety-related responsibilities they present.
\nThis chapter discusses expectations and ethical dilemmas concerning the use of HCRs that will interact with patients in medical and welfare settings in the future. These considerations have been made from the nurses’ perspective.
\nConversation with others is important to human beings. However, appropriate reactions and responses are complex, not just for HCRs, but also for traditional nurses. This means that, HCRs require improved functions, including specifications concerning appropriate listening practices, conversation, behavior, etc.
\nFurthermore, nurses must continue to protect the rights and safety of patients in all instances and at all times. Thus, HCRs should not be allowed to infringe on these principles in healthcare settings.
\nIn the future, HCRs may serve as patient interlocutors. Their conversation program may include AI with an interactive or transactive dialog function and the capacity to make decisions concerning ethical conflicts. To this end, discussion and collaboration with an interdisciplinary team is crucial to the process of developing these robots for use among patients.
\nThis work was partially supported by JSPS KAKENHI Grant Number JP19K10735. Part of this work was presented to the Japan Society of Mechanical Engineers in 2020.
\nThe authors declare no conflicts of interest.
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\n\nPlease consult our Open Access Funding page to explore some of these funding opportunities and learn more about how you could finance your IntechOpen publication. Keep in mind that this list is not definitive, and while we are constantly updating and informing our Authors of new funding opportunities, we recommend that you always check with your institution first.
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\n\nThe application process is open after your submitted manuscript has been accepted for publication. To apply, please fill out a Waiver Request Form and send it to your Author Service Manager. If you have an official letter from your university or institution showing that funds for your OA publication are unavailable, please attach that as well. The Waiver Request will normally be addressed within one week from the application date. All chapters that receive waivers or partial waivers will be designated as such online.
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\n\nNote: All data represented above was collected by IntechOpen from 2013 to 2017.
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