Phage as a Genetically Modifiable Supramacromolecule in Chemistry, Materials and Medicine.

Filamentous bacteriophage (phage) is a genetically modifiable supramacromolecule. It can be pictured as a semiflexible nanofiber (∼900 nm long and ∼8 nm wide) made of a DNA core and a protein shell with the former genetically encoding the latter. Although phage bioengineering and phage display techniques were developed before the 1990s, these techniques have not been widely used for chemistry, materials, and biomedical research from the perspective of supramolecular chemistry until recently. Powered by our expertise in displaying a foreign peptide on its surface through engineering phage DNA, we have employed phage to identify target-specific peptides, construct novel organic-inorganic nanohybrids, develop biomaterials for disease treatment, and generate bioanalytical methods for disease diagnosis. Compared with conventional biomimetic chemistry, phage-based supramolecular chemistry represents a new frontier in chemistry, materials science, and medicine. In this Account, we introduce our recent successful efforts in phage-based supramolecular chemistry, by integrating the unique nanofiber-like phage structure and powerful peptide display techniques into the fields of chemistry, materials science, and medicine: (1) successfully synthesized and assembled silica, hydroxyapatite, and gold nanoparticles using phage templates to form novel functional materials; (2) chemically introduced azo units onto the phage to form photoresponsive functional azo-phage nanofibers via a diazotization reaction between aromatic amino groups and the tyrosine residues genetically displayed on phage surfaces; (3) assembled phage into 2D films for studying the effects of both biochemical (the peptide sequences displayed on the phages) and biophysical (the topographies of the phage films) cues on the proliferation and differentiation of mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) and identified peptides and topographies that can induce their osteogenic differentiation; (4) discovered that phage could induce angiogenesis and osteogenesis for MSC-based vascularized bone regeneration; (5) identified novel breast cancer cell-targeting and MSC-targeting peptides and used them to significantly improve the efficiency of targeted cancer therapy and MSC-based gene delivery, respectively; (6) employed engineered phage as a probe to achieve ultrasensitive detection of biomarkers from serum of human patients for disease diagnosis; and (7) constructed centimeter-scale 3D multilayered phage assemblies with the potential application as scaffolds for bone regeneration and functional device fabrication. Our findings demonstrated that phage is indeed a very powerful supramacromolecule suitable for not only developing novel nanostructures and biomaterials but also advancing important fields in biomedicine, including molecular targeting, cancer diagnosis and treatment, drug and gene delivery, stem cell fate direction, and tissue regeneration. Our successes in exploiting phage in chemistry, materials, and medicine suggest that phage itself is nontoxic at the cell level and can be safely used for detecting biomarkers in vitro. Moreover, although we have demonstrated successful in vivo tissue regeneration induced by phage, we believe future studies are needed to evaluate the in vivo biodistribution and potential risks of the phage-based biomaterials.

Avoidable emergency department visits: a starting point.

OBJECTIVE: To better characterize and understand the nature of a very conservative definition of 'avoidable' emergency department (ED) visits in the United States to provide policymakers insight into what interventions can target non-urgent ED visits. DESIGN/SETTING: We performed a retrospective analysis of a very conservative definition of 'avoidable' ED visits using data from the National Hospital Ambulatory Medical Care Survey from 2005 to 2011. PARTICIPANTS: We examined a total of 115 081 records, representing 424 million ED visits made by patients aged 18-64 years who were seen in the ED and discharged home. MAIN OUTCOME MEASURES: We defined 'avoidable' as ED visits that did not require any diagnostic or screening services, procedures or medications, and were discharged home. RESULTS: In total, 3.3% (95% CI: 3.0-3.7) of all ED visits were 'avoidable.' The top five chief complaints included toothache, back pain, headache, other symptoms/problems related to psychosis and throat soreness. Alcohol abuse, dental disorders and depressive disorders were among the top three ICD-9 discharge diagnoses. Alcohol-related disorders and mood disorders accounted for 6.8% (95% CI: 5.7-8.0) of avoidable visits, and dental disorders accounted for 3.9% (95% CI: 3.0-4.8) of CCS-grouped discharge diagnoses. CONCLUSIONS: A significant number of 'avoidable' ED visits were for mental health and dental conditions, which the ED is not fully equipped to treat. Our findings provide a better understanding of what policy initiatives could potentially reduce these 'avoidable' ED visits to address the gaps in our healthcare system, such as increased access to mental health and dental care.

Salivary biomarkers: toward future clinical and diagnostic utilities.

The pursuit of timely, cost-effective, accurate, and noninvasive diagnostic methodologies is an endeavor of urgency among clinicians and scientists alike. Detecting pathologies at their earliest stages can significantly affect patient discomfort, prognosis, therapeutic intervention, survival rates, and recurrence. Diagnosis and monitoring often require painful invasive procedures such as biopsies and repeated blood draws, adding undue stress to an already unpleasant experience. The discovery of saliva-based microbial, immunologic, and molecular biomarkers offers unique opportunities to bypass these measures by utilizing oral fluids to evaluate the condition of both healthy and diseased individuals. Here we discuss saliva and its significance as a source of indicators for local, systemic, and infectious disorders. We highlight contemporary innovations and explore recent discoveries that deem saliva a mediator of the body's physiological condition. Additionally, we examine the current state of salivary diagnostics and its associated technologies, future aspirations, and potential as the preferred route of disease detection, monitoring, and prognosis.

Is dentistry going to get into the salivary diagnostics game or watch from the sidelines?

What is salivary diagnostics and why should you care? Most of us dentists try to avoid or control saliva as it interferes with access, or chemical interactions in dental materials or impression materials, or when it is simply a nuisance. Periodically, we may note reduced flow or encounter a patient with xerostomia. Correspondingly, we then manage the many of today's existing commercialized oral-based tests were yesterday's proposed ideas or concepts, captured in the 1993 New York Academy of Sciences Conference on oral based diagnostics. When coupled with the emerging point-of-care technology, the potential of salivary diagnostics is even more compelling. In this section, I hope to elucidate for the reader the potential of salivary diagnostics for the dental profession and So what is the value proposition? How could this disruptive technology serve the dentist and the patients they treat? What must occur to facilitate the ongoing development and introduction of salivary diagnostics into the marketplace?

A blocking-free microfluidic fluorescence heterogeneous immunoassay for point-of-care diagnostics.

In this article, a rapid, sensitive, and disposable microfluidic immunosensor is presented for point-of-care (POC) testing and clinical diagnosis. For the first time, the blocking process is eliminated from a microfluidic heterogeneous immunoassay by using protein A functionalized polydimethylsiloxane microchannels. The nonspecific binding of the assay is maintained around the chip background level by using a pair of antibodies with different affinity to protein A under optimized experimental conditions. C-reactive protein (CRP), a biomarker for inflammation and cardiovascular disease risk assessment, is selected as a model analyte to demonstrate the sensitivity of this blocking-free microfluidic heterogeneous immunoassay. A four parameter logistic function is used to model and assess the data. The limit of detection obtained is 0.54 µg/mL, which is lower than the cut-off value for clinical diagnosis. The overall assay is completed in 5 min. The protein A modified PDMS chips wet-stored at 4°C can maintain biofunctionality up to 14 months. The developed blocking-free microfluidic heterogeneous immunoassay will immediately provide benefits to most immunosensing microdevices targeted for POC diagnostics by shortening analysis time, simplifying fluid transportation, reducing sample consumption, and lowering waste generation.

Lipid characterization of human saliva.

Salivary lipids have been scarcely studied, and the reported results present disparities. This literature review is presented based on the importance of saliva as a diagnostic and/or prognostic medium for various diseases, its lipid content, and on its potential use for the analysis of nutritional markers that contribute to the study of diseases related to lipid consumption and metabolism.

Saliva: physiology and diagnostic potential in health and disease.

Saliva has been described as the mirror of the body. In a world of soaring healthcare costs and an environment where rapid diagnosis may be critical to a positive patient outcome, saliva is emerging as a viable alternative to blood sampling. In this review, we discuss the composition and various physiological roles of saliva in the oral cavity, including soft tissue protection, antimicrobial activities, and oral tissue repair. We then explore saliva as a diagnostic marker of local oral disease and focus particularly on oral cancers. The cancer theme continues when we focus on systemic disease diagnosis from salivary biomarkers. Communicable disease is the focus of the next section where we review the literature relating to the direct and indirect detection of pathogenic infections from human saliva. Finally, we discuss hormones involved in appetite regulation and whether saliva is a viable alternative to blood in order to monitor hormones that are involved in satiety.

[Significance of postmortem computed tomography in forensic autopsy and its possible issues].

Postmortem imaging (PMI) including computed tomography (CT) and magnetic resonance imaging (MRI) has become a familiar procedure in forensic casework. We investigated a short term impact of postmortem CT(PM-CT) in routine forensic autopsy cases at our institute during a period of 9 months (n = 121, fetus--92 year-old, 7 h--years postmortem), comparing to autopsy findings. In identification, PM-CT was useful for matching skeletal/dental characteristics, superimposing, and detection of foreign materials. However, conventional X-ray was often more effective for detection of small metallic foreign bodies. In pathomorphology, PM-CT partly demonstrated important findings for determining the immediate cause of death, which were confirmed by autopsy, but interpretation to the underlying/initiating/preceding causes of death or contributory factor(s) was mostly difficult or impossible. However, accumulated PM-CT data were useful for retrospective evaluation and review of autopsy findings. These experiences indicate that PMI is useful for radiographic screening and documentation, to be included in supplementary procedures, employing knowledge and experiences of forensic autopsy.

Responsive polymers for medical diagnostics.

Stimulus-responsive polymers have been used in improving the efficacy of medical diagnostics through different approaches including enhancing the contrast in imaging techniques and promoting the molecular recognition in diagnostic assays. This review overviews the mechanisms of stimulus-responsive polymers in response to external stimuli including temperature, pH, ion, light, etc. The applications of responsive polymers in magnetic resonance imaging, capture and purification of biomolecules through protein-ligand recognition and lab-on-a-chip technology are discussed.

The rise of bio-inspired polymer compartments responding to pathology-related signals.

Self-organized nano- and microscale polymer compartments such as polymersomes, giant unilamellar vesicles (GUVs), polyion complex vesicles (PICsomes) and layer-by-layer (LbL) capsules have increasing potential in many sensing applications. Besides modifying the physicochemical properties of the corresponding polymer building blocks, the versatility of these compartments can be markedly expanded by biomolecules that endow the nanomaterials with specific molecular and cellular functions. In this review, we focus on polymer-based compartments that preserve their structure, and highlight the key role they play in the field of medical diagnostics: first, the self-assembling abilities that result in preferred architectures are presented for a broad range of polymers. In the following, we describe different strategies for sensing disease-related signals (pH-change, reductive conditions, and presence of ions or biomolecules) by polymer compartments that exhibit stimuli-responsiveness. In particular, we distinguish between the stimulus-sensitivity contributed by the polymer itself or by additional compounds embedded in the compartments in different sensing systems. We then address necessary properties of sensing polymeric compartments, such as the enhancement of their stability and biocompatibility, or the targeting ability, that open up new perspectives for diagnostic applications.

Polydopamine-coated downconversion nanoparticle as an efficient dual-modal near-infrared-II fluorescence and photoacoustic contrast agent for non-invasive visualization of gastrointestinal tract in vivo.

Herein, a multifunctional dual-modal imaging probe is successfully developed to integrate the advantages of second near-infrared window (NIR-II, 1000-1700 nm) fluorescence imaging (FI) and photoacoustic imaging (PAI) with the ultimate goal of improving diseases diagnosis and management. Melanin-inspired polydopamine (PDA) polymer coated NaYF4:Yb3+,Er3+@NaYbF4@NaYF4:Nd3+ down conversion nanoparticles (DCNPs) is designed via water-in-oil microemulsion method, which comprises a DCNP core, acting as the NIR-II optical imaging agent, and a PDA shell, acting as the PA contrast agent. By taking the advantages of high spatial resolution and excellent temporal resolution, the dual-modal contrast agent is capable for high sensitivity real-time visualization of gastrointestinal tract, diagnosis of gastrointestinal peristalsis disorder and NIR-II FI-guided intestinal obstruction surgery. All of the above results demonstrate the great potential of DCNP@PDA NP as an efficient NIR-II/PAI dual-modal contrast agent for precision medicine.

Impact of time pressure on dentists' diagnostic performance.

OBJECTIVES: Although stress is prevalent amongst dentists, there is a paucity of data on the impact of stressors on dentists' clinical performance. To address this gap in the literature, the aim of the present study was to explore the role of time pressure, representing one common stressor, on dentists' radiographic diagnostic performance. METHODS: Forty dentists were randomised to examine and provide a radiographic report on two sets of radiographs (six bitewings in each set) under two conditions on a cross-over basis: time-pressure vs. no-time-pressure. The radiographic report of an experienced consultant was considered the gold standard against which participants diagnostic decisions were compared to calculate sensitivity and specificity. Participants rated their stress after each experimental condition using a 100 mm visual analogue scale (VAS). RESULTS: The VAS scores for stress were significantly higher in the time pressure condition vs. no time pressure condition (mean: 55.78 versus 10.73, p < 0.0001), indicating that the time pressure acted as a source of stress. Dentists' diagnostic performance was affected; the sensitivity was significantly lower under time pressure (median: 0.50 versus 0.80, p < 0.0001), but by contrast, the median diagnostic specificity was 1.00 under both conditions. CONCLUSIONS: Time pressure negatively impacts one aspect of dentists' diagnostic performance, namely sensitivity (increased diagnostic errors and omissions of pathology), which can potentially affect patient safety and the quality of care delivered. However, time pressure was found to have less influence on diagnostic specificity. CLINICAL SIGNIFICANCE: The present study demonstrated a significant deterioration of dentists' diagnostic performance (sensitivity) under time-pressure when examining bitewing radiographs. Diagnostic errors may put patient safety at risk, with patients potentially being harmed if pathology is missed. Such errors can have medicolegal implications on the dentists' practice.

Team-based learning using an audience response system: an innovative method of teaching diagnosis to undergraduate dental students.

A team-based learning (TBL) approach was used to facilitate student learning and performance in a sophomore preclinical endodontic course. TBL is based upon the division of a class into small groups of students using a problem-based learning approach. The purpose of this project was to improve student ability to diagnose diseases utilizing TBL combined with an audience response system (ARS). Three measures were used to assess the outcomes: 1) pre- and posttest scores, 2) a diagnostic skills assessment during the final examination, and 3) an attitudinal survey completed by the students. At the beginning of the course, second-year students (n=64) were evaluated to determine entry-level knowledge. Six groups of ten to eleven students each were pretested, followed by a parallel posttest following the implementation of the TBL experience. Students' performance on the posttest (63.4 percent) showed improved results when compared to the pretest (36.9 percent). Students also exhibited improved diagnostic skills with the final examination. The results of the students' attitudinal survey indicated an 80 percent agreement that TBL enhanced their powers of critical analysis.

MIASIS OCULAR Y BUCAL, A PROPÓSITO DE DOS CASOS / MYASIS EYE AND MOUTH, BY THE WAY OF TWO CASES

La palabra "miasis" proviene del griego, "myia" que significa mosca. La enfermedad corresponde a los daños causados por la invasión de larvas de moscas a tejidos del hombre u otros vertebrados

The term 'Myiasis' originates from the ancient Greek word 'myia', meaning 'fly'. This disease refers to tissue damage caused by the infestation of fly larvae in humans or other vertebrates

Diagnóstico de neurofibroma intraóseo solitario mandibular. Un reporte de caso / Diagnosis of mandibular solitary intraosseous neurofibroma, a case report

Introducción: el neurofbroma es una neoplasia benigna de la vaina de los nervios periféricos, eventualmente asociada a la neurofbromatosis tipo I, también llamada enfermedad de Von Recklinghausen. Su presentación a nivel de cabeza y cuello es poco común, por lo cual existen pocos reportes. Objetivo: presentar un caso clínico con diagnóstico de neurofbroma intraóseo clínico y una revisión actualizada de la literatura. Una paciente de 46 años, tratada en un servicio de cirugía oral y maxilofacial de la ciudad de Bogotá, Colombia, con un diagnóstico de neurofbroma intraóseo solitario de tres meses de evolución, a quien se le descartó neurofbromatosis de Von Recklinghausen, el cual comprometía el cuerpo y la rama mandibular derecha. El diagnóstico se realizó utilizando imágenes diagnósticas, así como bloques y láminas para la revisión de la biopsia inicial y de la resección. Esto, con el fn de interpretar y realizar el diagnóstico histopatológico en el Servicio de Patología Oral y Maxilofacial de la Facultad de Odontología de la Universidad Nacional de Colombia (FOUN), donde se efectuaron cortes en coloración de hematoxilina y eosina y marcadores de inmunohistoquímica. Conclusión: el tratamiento realizado incluyó la resección quirúrgica de la lesión, injerto óseo y recubrimiento con membrana alogénica de dermis humana.

Neurofbroma is a benign neoplasm of the peripheral nerves sheath, eventually associated with neurofbromatosis type I, also called Von Recklinghausen disease, its presentation at the head and neck level is rare, therefore, reports are scarce. A clinical case with diagnosis of "Solitary intraosseous neurofbroma" ruling out Von Recklinghausen Neurofbromatosis by genetic studies in a 46-year-old female patient, which compromises the right mandibular body and ramus of three months of evolution is presented. Diagnostic images, blocks and slides were used for revision of the initial biopsy, cuts of the resection with hematoxylin and eosin staining and immunohistochemical markers were done for interpretation and histopathological diagnosis. The treatment performed included surgical resection of the lesion, bone graft, and allogeneic human dermis membrane coverage. The aim of this article is to present a case with diagnosis

Integration of sample preparation and analysis into an optofluidic chip for multi-target disease detection.

Detection of molecular biomarkers with high specificity and sensitivity from biological samples requires both sophisticated sample preparation and subsequent analysis. These tasks are often carried out on separate platforms which increases required sample volumes and the risk of errors, sample loss, and contamination. Here, we present an optofluidic platform which combines an optical detection section with single nucleic acid strand sensitivity, and a sample processing unit capable of on-chip, specific extraction and labeling of nucleic acid and protein targets in complex biological matrices. First, on-chip labeling and detection of individual lambda DNA molecules down to concentrations of 8 fM is demonstrated. Subsequently, we demonstrate the simultaneous capture, fluorescence tagging and detection of both Zika specific nucleic acid and NS-1 protein targets in both buffer and human serum. We show that the dual DNA and protein assay allows for successful differentiation and diagnosis of Zika against cross-reacting species like dengue.

Exploring the Integration of the Dental Hygiene Diagnosis in Entry-Level Dental Hygiene Curricula.

Purpose: The purpose of this study was to investigate how dental hygiene educational programs currently incorporate dental hygiene diagnosis (DHDx) into entry-level, dental hygiene curriculum.Methods: An exploratory, quantitative, descriptive cross-sectional study was designed to assess the extent to which DHDx is integrated into entry-level dental hygiene curriculum. A 30-item survey was designed and content validity established using a subset of dental hygiene faculty and researchers as well as participants from the American Dental Hygienists' Association. Data was collected using the Qualtrics® electronic platform; two electronic mailings were sent to all entry-level dental hygiene programs. All surveys included a consent form and confidentiality was maintained. Descriptive statistics were used to analyze data.Results: Of the 334 surveys e-mailed, 198 responses (n=198) were received for a 59% response rate. Of the program respondents, 98% (n=191) reported that the dental hygiene process of care and concepts specifically relating to the DHDx were being taught. In addition, 79% (n=153) of respondents confirmed that they "always" require students to write a DHDx statement for the patients. Of the respondents, 80% (n=150) recognized that formulating a DHDx should result in improved patient outcomes and 76% (n=143) indicated that formulating a DHDx increases the dental hygienist's accountability in patient care.Conclusion: This exploratory study assessed the extent to which the DHDx is taught in entry-level dental hygiene programs. Findings confirmed that the DHDx is an integral component of dental hygiene education, but there is a need for standardization and faculty calibration for DHDx concepts and terminology. These results support adding DHDx into the Commission on Dental Accreditation (CODA) standards.

Does the rehabilitation treatment predispose the patient with cleft to endodontic treatment?

Aim: to verify the relation between endodontic treatment of teeth adjacent to the cleft area and the rehabilitation of patients with unilateral cleft lip and palate, at the Hospital for Rehabilitation of Craniofacial Anomalies. Methods: the present split-mouth study was composed of 406 individuals with complete unilateral cleft lip and palate who had completed the rehabilitation process in a single tertiary cleft center (55.9% males). The information was collected from the dental history on the patients' records and radiographs. The frequency of endodontic treatment in the upper incisors and canines was calculated for the cleft and non-cleft sides. The comparison between sides was performed by the chi-square test (p <0.05). Results: endodontic treatment was more frequent in teeth adjacent to the cleft than in contralateral teeth. The frequency of endodontic treatment in at least one tooth adjacent to the cleft was 18.97%, and 11.6% on the contralateral side. It was observed that endodontic treatment was necessary in 63.5% of patients who had been submitted to orthodontic treatment, 42.4% of those rehabilitated with fixed partial dentures and 12.0% of patients who underwent dental reshaping of teeth adjacent to the cleft. The treatments performed included vital pulp therapy (46.1%), non-vital pulp therapy (46.8%) and endodontic retreatment (7.1%). Conclusion: in individuals with complete cleft lip and palate, teeth close to the bone defect area and used for rehabilitation treatment presented greater need of endodontic intervention

A radiation free alternative to CBCT volumetric rendering for soft tissue evaluation / Um método alternativo à TCFC sem radiação ionizante para a avaliação de tecidos moles da face

Objective: The aim of the present study is to evaluate whether a "radiation free" method using 3D facial scan can replace Cone Beam Computed Tomography (CBCT) volumetric rendering of soft tissue of the patient to assess maxillofacial surgery outcomes and compare the reference points and angular measurements of patient facial soft tissue. Material and Methods: Facial soft tissue scan of the patient's face, before and after orthognathic surgery and a CBCT of the skull for volumetric rendering of soft tissues were carried out. The 3D acquisitions were processed using Planmeca ProMax 3D ProFace® software (Planmeca USA, Inc.; Roselle, Illinois, USA). The participant were positioned in a natural position during the skull scannering. Three sagittal angular measurements were performed (Tr-NA, Tr-N-Pg, Ss-N-Pg) and two verticals (Go-N-Me, Tr-Or-Pg) on facial soft tissue scan and on the patient's 3D soft tissue CBCT volumetric rendering. Results: A certain correspondence has been demonstrated between the measurements obtained on the Proface and those on the CBCT. Conclusion: A radiation free method was to be considered an important diagnostic tool that works in conditions of not subjecting the patient to harmful ionizing radiation and it was therefore particularly suitable for growing subjects. The soft tissue analysis based on the realistic facial scan has shown sufficient reliability and reproducibility even if further studies are needed to confirm the research result.(AU)

Objetivo:Avaliar se um método "livre de radiação" usando escaneamento facial 3D pode substituir a renderização volumétrica da tomografia computadorizada de feixe cônico (TCFC) dos tecidos moles do paciente para analisar os resultados da cirurgia maxilofacial e comparar os pontos de referência e medições angulares afim de avaliar a correspondência entre as duas metodologias. Material e Métodos: Foi realizado o escaneamento dos tecidos moles faciais do paciente, antes e depois da cirurgia ortognática e uma tomografia computadorizada de feixe cônico do crânio para renderização volumétrica dos tecidos moles. As aquisições 3D foram processadas usando o software Planmeca ProMax 3D ProFace® (Planmeca USA, Inc.; Roselle, Illinois, USA). O participante foi posicionado em posição natural durante o escaneamento do crânio. Três medições angulares sagitais foram realizadas (Tr-NA, Tr-N-Pg, Ss-N-Pg) e duas verticais (Go-N-Me, Tr-Or-Pg) nas imagens de scaneamento e nas imagens do tecido mole facial da reconstrução tridimensional da TCFC. Resultados: Uma certa correspondência foi demonstrada entre as medidas obtidas no Proface® e aquelas na TCFC. Conclusão: Um método livre de radiação deve ser considerado uma importante ferramenta de diagnóstico que funciona em condições de não submeter o paciente a radiação ionizante nociva e, portanto, é particularmente adequado para indivíduos em crescimento. A análise de tecidos moles com base na varredura facial realista mostrou confiabilidade e reprodutibilidade, porém mais estudos são necessários para confirmar o resultado da pesquisa. (AU)