Dental enamel is the hardest and most mineralized tissue in extinct and extant vertebrate species and provides maximum durability that allows teeth to function as weapons and/or tools as well as for ...food processing. Enamel development and mineralization is an intricate process tightly regulated by cells of the enamel organ called ameloblasts. These heavily polarized cells form a monolayer around the developing enamel tissue and move as a single forming front in specified directions as they lay down a proteinaceous matrix that serves as a template for crystal growth. Ameloblasts maintain intercellular connections creating a semi-permeable barrier that at one end (basal/proximal) receives nutrients and ions from blood vessels, and at the opposite end (secretory/apical/distal) forms extracellular crystals within specified pH conditions. In this unique environment, ameloblasts orchestrate crystal growth via multiple cellular activities including modulating the transport of minerals and ions, pH regulation, proteolysis, and endocytosis. In many vertebrates, the bulk of the enamel tissue volume is first formed and subsequently mineralized by these same cells as they retransform their morphology and function. Cell death by apoptosis and regression are the fates of many ameloblasts following enamel maturation, and what cells remain of the enamel organ are shed during tooth eruption, or are incorporated into the tooth's epithelial attachment to the oral gingiva. In this review, we examine key aspects of dental enamel formation, from its developmental genesis to the ever-increasing wealth of data on the mechanisms mediating ionic transport, as well as the clinical outcomes resulting from abnormal ameloblast function.
Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used RNA sequence data generated by Genotype-Tissue Expression (GTEx) project to ...investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples. These signatures are dominated by a relatively small number of genes–which is most clearly seen in blood–though few are exclusive to a particular tissue and vary more across tissues than individuals. Genes exhibiting high interindividual expression variation include disease candidates associated with sex, ethnicity, and age. Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program. Variation in splicing, despite its stochasticity, may play in contrast a comparatively greater role in defining individual phenotypes.
A panel of experts convened by the American Dental Association (ADA) Council on Scientific Affairs presents evidence-based clinical recommendations regarding professionally applied and ...prescription-strength, home-use topical fluoride agents for caries prevention. These recommendations are an update of the 2006 ADA recommendations regarding professionally applied topical fluoride and were developed by using a new process that includes conducting a systematic review of primary studies.
The authors conducted a search of MEDLINE and the Cochrane Library for clinical trials of professionally applied and prescription-strength topical fluoride agents--including mouthrinses, varnishes, gels, foams and pastes--with caries increment outcomes published in English through October 2012.
The panel included 71 trials from 82 articles in its review and assessed the efficacy of various topical fluoride caries-preventive agents. The panel makes recommendations for further research.
The panel recommends the following for people at risk of developing dental caries: 2.26 percent fluoride varnish or 1.23 percent fluoride (acidulated phosphate fluoride) gel, or a prescription-strength, home-use 0.05 percent fluoride gel or paste or 0.09 percent fluoride mouthrinse for patients 6 years or older. Only 2.26 percent fluoride varnish is recommended for children younger than 6 years. The strengths of the recommendations for the recommended products varied from "in favor" to "expert opinion for." As part of the evidence-based approach to care, these clinical recommendations should be integrated with the practitioner's professional judgment and the patient's needs and preferences.
Aim This pilot study examines how rural and remote junior doctors' career decisions are influenced by collegial relationships within the discipline of general paediatrics. Methods Social network ...analysis (SNA) was undertaken by structured interviews with 10 paediatricians working in regional towns in Western Australia. UNICET software was used to determine the interactions between individual networks to look for overlap and common influencers. Results Ten rural paediatricians were interviewed. An individual was found to have key measures of centrality at the core of the entire social network of rural general paediatricians. This included a high degree of ‘betweenness’ (connections within social networks), and a high broker index (connections between separate areas of a network or between networks) demonstrated by that person combining three disconnected networks into a single coherent network. This central individual was a recently appointed consultant with links to senior paediatricians, peers and junior trainees, and may be instrumental in recruitment and retention in the rural paediatric workforce. Conclusion Improving understanding of the impact of social networks, and decision‐making processes that influence rural career choices, can inform innovative solutions to develop sustainable strategies for recruiting and retaining the rural paediatric workforce. Applying this model on a larger scale may provide more data to support evidence‐based programmes that enable this within the Australian context.
Interferon (IFN) was discovered based on interference with virus production, and three types of IFN are now defined. Since its discovery, IFN’s roles have expanded beyond viruses to diverse pathogen ...types, tissue homeostasis, and inflammatory disease. The gastrointestinal (GI) tract is arguably the tissue where the roles of IFN types are most distinct, with a particularly prominent role for type-III IFN in antiviral protection of the intestinal epithelium. Current studies continue to deepen our understanding of the type- and tissue-specific roles of IFN. This review highlights these advances within the GI tract, including discovery of protective roles for type-III IFNs against nonviral GI pathogens, and discovery of an antiviral homeostatic type-III IFN response within the intestinal epithelium.
One of the promises of the experience sampling methodology (ESM) is that a statistical analysis of an individual's emotions, cognitions and behaviors in everyday-life could be used to identify ...relevant treatment targets. A requisite for clinical implementation is that outcomes of such person-specific time-series analyses are not wholly contingent on the researcher performing them.
To evaluate this, we crowdsourced the analysis of one individual patient's ESM data to 12 prominent research teams, asking them what symptom(s) they would advise the treating clinician to target in subsequent treatment.
Variation was evident at different stages of the analysis, from preprocessing steps (e.g., variable selection, clustering, handling of missing data) to the type of statistics and rationale for selecting targets. Most teams did include a type of vector autoregressive model, examining relations between symptoms over time. Although most teams were confident their selected targets would provide useful information to the clinician, not one recommendation was similar: both the number (0–16) and nature of selected targets varied widely.
This study makes transparent that the selection of treatment targets based on personalized models using ESM data is currently highly conditional on subjective analytical choices and highlights key conceptual and methodological issues that need to be addressed in moving towards clinical implementation.
•Intensive longitudinal time-series data can identify personalized treatment targets.•Twelve research labs varied in how they analyzed one patient's time-series data.•Moreover, they varied widely in selected treatment targets and the underlying rationale.•Results of person-specific analyses are currently conditional on subjective choices.
Continuous-flow left ventricular assist devices (LVAD) have emerged as the standard of care for advanced heart failure patients requiring long-term mechanical circulatory support. Evidence-based ...clinical management of LVAD-supported patients is becoming increasingly important for optimizing outcomes. In this state-of-art review, we propose key elements in managing patients supported with the new continuous-flow LVADs. Although most of the presented information is largely based on investigator experience during the 1,300-patient HeartMate II clinical trial, many of the discussed principles can be applied to other emerging devices as well. Patient selection, pre-operative preparation, and the timing of LVAD implant are some of the most important elements critical to successful circulatory support and are principles universal to all devices. In addition, proper nutrition management and avoidance of infectious complications can significantly affect morbidity and mortality during LVAD support. Optimizing intraoperative and peri-operative care, and the monitoring and treatment of other organ system dysfunction as it relates to LVAD support, are discussed. A multidisciplinary heart failure team must be organized and charged with providing comprehensive care from initial referral until support is terminated. Preparing for hospital discharge requires detailed education for the patient and family or friends, with provisions for emergencies and routine care. Implantation techniques, troubleshooting device problems, and algorithms for outpatient management, including the diagnosis and treatment of related problems associated with the HeartMate II, are discussed as an example of a specific continuous-flow LVAD. Ongoing trials with other continuous-flow devices may produce additional information in the future for improving clinical management of patients with these devices.
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The number of biological molecules emerging as therapeutics is growing exponentially due to their higher specificity and tolerability profiles compared to small molecules. Despite ...this, their traditionally parenteral delivery often results in poor patient compliance and incomplete treatment. Current research is focussed on developing effective oral delivery strategies to facilitate administration of these biomolecules, however no universal method exists to simultaneously provide gastric protection as well as enhance transport across the gastrointestinal epithelium. Furthermore, for efficient formulation development it is imperative that we can reliably analyse permeability of biomolecules through the gastrointestinal tract, highlighting the importance of the continual development and ongoing evaluation of in vitro predictive permeability tools. Here, we review the physiological obstacles associated with peptide and protein delivery throughout the gastrointestinal tract. Furthermore, we highlight methods utilised to circumvent these barriers and promote improved intestinal permeability. Lastly, we explore in vitro models employed to predict epithelial transport. Key findings highlight the need to carefully understand gastrointestinal physiology, allowing specific engineering of oral delivery systems for biomolecules. Significant importance is placed upon understanding enzymatic degradation susceptibility as well as uptake mechanisms for particulate and protein-based therapeutics for the development of successful oral protein delivery platforms.
The craniofacial and oral manifestations of the different epidermolysis bullosa (EB) types vary markedly in character and severity depending largely on the EB type. The tissues affected and the ...phenotypes displayed are closely related to the specific abnormal or absent proteins resulting from the causative genetic mutations for these disorders. In this article, the major oral manifestations are reviewed for different EB subtypes and are related to the causative genetic mutations and gene expression.
Hypoplastic left heart syndrome Barron, David J, FRCS; Kilby, Mark D, Prof; Davies, Ben, PhD ...
The Lancet (British edition),
08/2009, Letnik:
374, Številka:
9689
Journal Article
Recenzirano
Summary Hypoplastic left heart syndrome is a rare congenital heart defect in which the left side of the heart is underdeveloped. Surgical management of hypoplastic left heart syndrome has changed the ...prognosis of the condition that was previously regarded as fatal. We discuss surgical strategies based on staged procedures, with the right ventricle supporting both systemic and pulmonary circulation. We also discuss other management options, such as neonatal transplantation and the recent innovation of hybrid techniques. Surgical techniques and the understanding of the pathophysiology of this condition have been at the forefront of neonatal cardiac surgery and intensive care. The management of the syndrome remains a challenge because affected children grow into adolescence and adulthood posing various new problems and demands.
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