THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

The Design and Analysis of Experiments

An adequate supply of saliva is critical to the preservation and maintenance of oral tissue. Clinicians often do not value the many benefits of saliva until quantities are decreased. Much is written on the subject of salivary hypofunction, but little attention is paid to normal salivary flow and function. This article is a brief, up-to-date overview of the literature on the basics of normal salivary composition, flow, and function. A review of the literature was conducted using MEDLINE and Healthstar (1944 through 1999); articles were selected for inclusion on the basis of relevance and significance to the clinician.

A review of saliva: Normal composition, flow, and function

Because of the high catalytic activities and substrate specificity, natural enzymes have been widely used in industrial, medical, and biological fields, etc. Although promising, they often suffer from intrinsic shortcomings such as high cost, low operational stability, and difficulties of recycling. To overcome these shortcomings, researchers have been devoted to the exploration of artificial enzyme mimics for a long time. Since the discovery of ferromagnetic nanoparticles with intrinsic horseradish peroxidase-like activity in 2007, a large amount of studies on nanozymes have been constantly emerging in the next decade. Nanozymes are one kind of nanomaterials with enzymatic catalytic properties. Compared with natural enzymes, nanozymes have the advantages such as low cost, high stability and durability, which have been widely used in industrial, medical, and biological fields. A thorough understanding of the possible catalytic mechanisms will contribute to the development of novel and high-efficient nanozymes, and the rational regulations of the activities of nanozymes are of great significance. In this review, we systematically introduce the classification, catalytic mechanism, activity regulation as well as recent research progress of nanozymes in the field of biosensing, environmental protection, and disease treatments, etc. in the past years. We also propose the current challenges of nanozymes as well as their future research focus. We anticipate this review may be of significance for the field to understand the properties of nanozymes and the development of novel nanomaterials with enzyme mimicking activities.

Nanozymes: Classification, Catalytic Mechanisms, Activity Regulation, and Applications

Background and Overview Dental caries is a bacterially based disease. When it progresses, acid produced by bacterial action on dietary fermentable carbohydrates diffuses into the tooth and dissolves the carbonated hydroxyapatite mineral—a process called demineralization. Pathological factors including acidogenic bacteria (mutans streptococci and lactobacilli), salivary dysfunction, and dietary carbohydrates are related to caries progression. Protective factors—which include salivary calcium, phosphate and proteins, salivary flow, fluoride in saliva, and antibacterial components or agents—can balance, prevent or reverse dental caries. Conclusions Caries progression or reversal is determined by the balance between protective and pathological factors. Fluoride, the key agent in battling caries, works primarily via topical mechanisms: inhibition of demineralization, enhancement of remineralization and inhibition of bacterial enzymes. Clinical Implications Fluoride in drinking water and in fluoride-containing products reduces caries via these topical mechanisms. Antibacterial therapy must be used to combat a high bacterial challenge. For practical caries management and prevention or reversal of dental caries, the sum of the preventive factors must outweigh the pathological factors.

The science and practice of caries prevention

Nanozymes are nanomaterial-based artificial enzymes. By effectively mimicking catalytic sites of natural enzymes or harboring multivalent elements for reactions, nanozyme systems have successfully served as direct surrogates of traditional enzymes for catalysis. With the rapid development and ever-deepening understanding of nanotechnology, nanozymes offer higher catalytic stability, ease of modification and lower manufacturing cost than protein enzymes. Additionally, nanozymes possess inherent nanomaterial properties, providing not only a simple substitute of enzymes but also a multimodal platform interfacing complex biologic environments. Recent extensive research has focused on designing various nanozyme systems that are responsive to one or multiple substrates by tailored means. Catalytic activities of nanozymes can be regulated by pH, H2O2 and glutathione concentrations and levels of oxygenation in different microenvironments. Moreover, nanozymes can be remotely-controlled via different stimuli, including a magnetic field, light, ultrasound, and heat. Collectively, these factors can be adjusted to maximize the diagnostic and therapeutic efficacies of different diseases in biomedical settings. Therefore, by integrating the catalytic property and inherent nanomaterial nature of nanozyme systems, we anticipate that stimuli-responsive nanozymes will open up new horizons for diagnosis, treatment, and theranostics.

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Nanozyme: new horizons for responsive biomedical applications.

Acids of intrinsic and extrinsic origin are thought to be the main etiologic factors for dental erosion. There is evidence that acidic foodstuffs and beverages play a role in the development of erosion. However, the pH of a dietary substance alone is not predictive of its potential to cause erosion as other factors modify the erosive process. These factors are chemical (pKa values, adhesion and chelating properties, calcium, phosphate and fluoride content), behavioural (eating and drinking habits, life style, excessive consumption of acids) and biological (flow rate, buffering capacity, composition of saliva, pellicle formation, tooth composition, dental and soft tissue anatomy). The interplay between erosion and abrasion (specially oral hygiene practices) may be the main driver leading to the clinical manifestation of this disorder. Recommendations for patients at risk for dental erosion such as reducing acid exposure by reducing the frequency and contact of acids will be discussed.

The Role of Diet in the Aetiology of Dental Erosion

The extrinsic causes of dental erosion can be grouped under the headings of environmental, diet, medications and lifestyle. Environmental factors mainly involve exposure to acid fumes by workers in factories without proper safeguards. Swimming pools with low pH due to inadequate maintenance have also been implicated. Dietary factors have received the most attention and are likely to affect the broadest segment of the population. Most acidic foods and drinks have the potential to cause dental erosion in the human mouth. The total acid level (titratable acid) of dietary substances is considered more important than their pH, because it will determine the actual H+ available to interact with the tooth surface. Other constituents of foods and beverages will also have a modifying effect, including the calcium, phosphate and fluoride concentration, the acid type, and physical and chemical properties that influence the clearance rate from the mouth. It is not appropriate to assign relative degrees of risk to the different dietary substances except in general categories, because of the many human biological and behavioral factors that influence the clinical expression of dental erosion. The types of foods and beverages consumed, and the frequency and time of consumption are lifestyle factors that are considered most important regarding the clinical development of dental erosion. Low pH medications and oral hygiene products have also been suggested as potential causes of erosion. The combination of frequent consumption of acidic substances and overzealous oral hygiene practices may be another high risk lifestyle factor.

Etiology of dental erosion--extrinsic factors.

A barrier to providing sealants is concern about inadvertently sealing over caries. This meta-analysis examined the effectiveness of sealants in preventing caries progression. We searched electronic databases for comparative studies examining caries progression in sealed permanent teeth. We used a random-effects model to estimate percentage reduction in the probability of caries progression in sealed vs. unsealed carious teeth. Six studies, including 4 randomized-controlled trials (RCT) judged to be of fair quality, were included in the analysis (384 persons, 840 teeth, and 1090 surfaces). The median annual percentage of non-cavitated lesions progressing was 2.6% for sealed and 12.6% for unsealed carious teeth. The summary prevented fraction for RCT was 71.3% (95%CI: 52.8%-82.5, no heterogeneity) up to 5 years after placement. Despite variation among studies in design and conduct, sensitivity analysis found the effect to be consistent in size and direction. Sealing non-cavitated caries in permanent teeth is effective in reducing caries progression.

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The Effectiveness of Sealants in Managing Caries Lesions

By using in situ models, we have the potential to study both fundamental aspects of the caries process as well as more applied research problems such as the effect of food on dental caries and the role of fluoride in caries prevention in human subjects without actually causing caries in the natural dentition. The key experimental parameters that need to be considered in the development of an in situ model are the characteristics of the subject panel, the physical design of the model, the type of hard tissue substrate and the method of assessing mineral status, and the study design and clinical protocol. Each parameter must be carefully considered in relation to the objectives of the research, study design requirements, ethical considerations, impact on clinical relevance, and impact on the control of variation. The major source of variation associated with in situ models should be of biological and not experimental origin. The design and conduct of proper in situ model studies require a clear understanding of the caries process, sound analytical support, and a knowledge of how to work with research subjects to achieve a high level of compliance. Given the complex nature of caries, a combination of hard tissue substrates--including sound, surface-softened lesions and subsurface lesions--may be necessary to model all aspects of caries progression and prevention successfully. Internal validation of in situ models using fluoride dose-response controls is considered to be necessary for studies evaluating the efficacy of new fluoride dentifrice formulations.

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Domenick T. Zero

Papers

The Role of Diet in the Aetiology of Dental Erosion

Etiology of dental erosion--extrinsic factors.

The Effectiveness of Sealants in Managing Caries Lesions

In situ caries models.

Erosion — chemical and biological factors of importance to the dental practitioner