Prevalence of oral and maxillofacial lesions in children and adolescents at a regional Brazilian oral pathology service: a retrospective study and the relevant literature review.

Purpose: This study assessed the prevalence of maxillofacial lesions in children, i.e., 0-9 years, and adolescents, i.

Prevalence of oral mucosal disorders during pregnancy: A systematic review and meta-analysis.

Objective: To assess the prevalence of oral mucosal disorders during pregnancy.

Methods: Observational studies were selected by two reviewers in a two-phase process. Search strategies were applied at CINAHL, LILACS, LIVIVO, PubMed, Scopus, Web of Science, Google Scholar, OpenGrey, and ProQuest.

Proteostasis regulation by the ubiquitin system.

Cells have developed an evolutionary obligation to survey and maintain proteome fidelity and avoid the possible toxic consequences of protein misfolding and aggregation. Disturbances to protein homoeostasis (proteostasis) can result in severe cellular phenotypes and are closely linked with the accumulation of microscopically visible deposits of aggregated proteins. These include inclusion bodies found in AD (Alzheimer's disease), HD (Huntington's disease) and ALS (amyotrophic lateral sclerosis) patient neurons.

UBQLN2 Mediates Autophagy-Independent Protein Aggregate Clearance by the Proteasome.

Clearance of misfolded and aggregated proteins is central to cell survival. Here, we describe a new pathway for maintaining protein homeostasis mediated by the proteasome shuttle factor UBQLN2. The 26S proteasome degrades polyubiquitylated substrates by recognizing them through stoichiometrically bound ubiquitin receptors, but substrates are also delivered by reversibly bound shuttles.

Ubiquitin C-terminal hydrolases cleave isopeptide- and peptide-linked ubiquitin from structured proteins but do not edit ubiquitin homopolymers.

Modification of proteins with ubiquitin (Ub) occurs through a variety of topologically distinct Ub linkages, including Ube2W-mediated monoubiquitylation of N-terminal alpha amines to generate peptide-linked linear mono-Ub fusions. Protein ubiquitylation can be reversed by the action of deubiquitylating enzymes (DUBs), many of which show striking preference for particular Ub linkage types. Here, we have screened for DUBs that preferentially cleave N-terminal Ub from protein substrates but do not act on Ub homopolymers.

Developing clinical cancer genetics services in resource-limited countries: the case of retinoblastoma in Kenya.

Background/aims: Clinical cancer genetics is an integral part of cancer control and management, yet its development as an essential medical service has been hindered in many low-and-middle-income countries. We report our experiences in developing a clinical cancer genetics service for retinoblastoma in Kenya.

Methods: A genetics task force was created from within the membership of the existing Kenyan National Retinoblastoma Strategy group.

SiRNA screening to identify ubiquitin and ubiquitin-like system regulators of biological pathways in cultured mammalian cells.

Post-translational modification of proteins with ubiquitin and ubiquitin-like molecules (UBLs) is emerging as a dynamic cellular signaling network that regulates diverse biological pathways including the hypoxia response, proteostasis, the DNA damage response and transcription. To better understand how UBLs regulate pathways relevant to human disease, we have compiled a human siRNA "ubiquitome" library consisting of 1,186 siRNA duplex pools targeting all known and predicted components of UBL system pathways. This library can be screened against a range of cell lines expressing reporters of diverse biological pathways to determine which UBL components act as positive or negative regulators of the pathway in question.

Pre-hospital fibrinolysis in the management of patients with ST elevation acute coronary syndrome: review of the evidence, implementation and future directions.

Time to reperfusion is among the strongest predictors of clinical outcome in patients who present with ST elevation acute myocardial infarction. When time to access is equivalent, primary percutaneous coronary intervention has demonstrated superior outcomes to fibrinolysis. However, where significant delays exist in accessing percutaneous intervention, fibrinolysis has an important role.

The P-body component USP52/PAN2 is a novel regulator of HIF1A mRNA stability.

HIF1A (hypoxia-inducible factor 1α) is the master regulator of the cellular response to hypoxia and is implicated in cancer progression. Whereas the regulation of HIF1A protein in response to oxygen is well characterized, less is known about the fate of HIF1A mRNA. In the present study, we have identified the pseudo-DUB (deubiquitinating enzyme)/deadenylase USP52 (ubiquitin-specific protease 52)/PAN2 [poly(A) nuclease 2] as an important regulator of the HIF1A-mediated hypoxic response.

Successes and Challenges in an Integrated Tuberculosis/HIV Clinic in a Rural, Resource-Limited Setting: Experiences from Kericho, Kenya.

Objective. To describe TB/HIV clinic outcomes in a rural, Ministry of Health hospital. Design.

Suppression of protein aggregation by chaperone modification of high molecular weight complexes.

Protein misfolding and aggregation are associated with many neurodegenerative diseases, including Huntington's disease. The cellular machinery for maintaining proteostasis includes molecular chaperones that facilitate protein folding and reduce proteotoxicity. Increasing the protein folding capacity of cells through manipulation of DNAJ chaperones has been shown to suppress aggregation and ameliorate polyglutamine toxicity in cells and flies.

The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.

Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA). AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free FAT10 and FAT10ylated proteins and can form a ternary complex with FAT10 and NUB1.

Anti-Platelet Therapy for Acute Coronary Syndrome: A Review of Currently Available Agents and What the Future Holds.

Dual anti-platelet therapy remains a cornerstone in the management of patients suffering from acute coronary syndromes (ACS). The combination of aspirin and clopidogrel has been shown to result in significant reductions in cardiovascular end points including recurrent infarction and death in several randomised control trial of patients with ACS. However, many patients still experience ischaemic events on the combination of aspirin and clopidogrel.

High-dose tirofiban with enoxaparin and inflammatory markers in high-risk percutaneous intervention.

Aim: The study assessed the benefit of high bolus dose tirofiban (HD-tirofiban) with enoxaparin compared with HD-tirofiban with unfractionated heparin (UFH). The study examined markers of platelet activation, thrombin generation and inflammation.

Materials And Methods: The study is a prospective single centre open-label trial of patients with high-risk acute coronary syndrome treated with percutaneous intervention (PCI) who were randomized to anticoagulation with UFH or enoxaparin with HD-tirofiban (25 microg kg(-1) bolus).

The polyubiquitin Ubc gene modulates histone H2A monoubiquitylation in the R6/2 mouse model of Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disease caused by the expansion of a polyglutamine tract in the protein huntingtin (htt). HD brains are characterized by the presence of ubiquitin-positive neuronal inclusion bodies, suggesting that disturbances in the distribution of cellular ubiquitin may contribute to disease pathology. The fact that several neurodegenerative diseases are caused by mutations in ubiquitin-processing enzymes and that the polyubiquitin genes are required for resistance to cellular stress led us to investigate the effect of perturbing the ubiquitin system in HD.

The ubiquitin-proteasome reporter GFPu does not accumulate in neurons of the R6/2 transgenic mouse model of Huntington's disease.

Impairment of the ubiquitin-proteasome system (UPS) has long been considered an attractive hypothesis to explain the selective dysfunction and death of neurons in polyglutamine disorders such as Huntington's disease (HD). The fact that inclusion bodies in HD mouse models and patient brains are rich in ubiquitin and proteasome components suggests that the UPS may be hindered directly or indirectly by inclusion bodies or their misfolded monomeric or oligomeric precursors. However, studies into UPS function in various polyglutamine disease models have yielded conflicting results, suggesting mutant polyglutamine tracts may exert different effects on the UPS depending on protein context, expression level, subcellular localisation and cell-type.

Molecular chaperones and photoreceptor function.

Molecular chaperones facilitate and regulate protein conformational change within cells. This encompasses many fundamental cellular processes: including the correct folding of nascent chains; protein transport and translocation; signal transduction and protein quality control. Chaperones are, therefore, important in several forms of human disease, including neurodegeneration.

Patient delay in responding to symptoms of possible heart attack: can we reduce time to care?

In Australia, many deaths and significant cardiac disability result from delayed response to symptoms of heart attack. Although delays due to transport and initiation of reperfusion therapy in hospital may contribute to late treatment, the major component of delay is the time patients take in deciding to seek help. A critical examination of campaigns to shorten patient delay concludes that they were based on a factual, short-term, non-targeted approach that included education and mass media strategies.

Measurement of myocardial fractional flow reserve is a cost-effective way to identify coronary artery lesions of indeterminate severity that warrant revascularisation.

Background: The RADI pressure wire may be used in stenotic coronary arteries to calculate myocardial fractional flow reserve (FFR(myo)), the ratio between distal hyperaemic coronary pressure and aortic pressure. A ratio less than 0.75 categorizes lesions of haemodynamic significance for which percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) may be warranted.

Proteasome impairment does not contribute to pathogenesis in R6/2 Huntington's disease mice: exclusion of proteasome activator REGgamma as a therapeutic target.

Huntington's disease (HD) is one of a group of neurodegenerative disorders caused by the pathological expansion of a glutamine tract. A hallmark of these so-called polyglutamine diseases is the presence of ubiquitylated inclusion bodies, which sequester various components of the 19S and 20S proteasomes. In addition, the ubiquitin-proteasome system (UPS) has been shown to be severely impaired in vitro in cells overexpressing mutant huntingtin.

Platelet-monocyte aggregates predict troponin rise after percutaneous coronary intervention and are inhibited by Abciximab.

Background: Platelet-monocyte aggregates and other markers of platelet activation were investigated before and after percutaneous coronary intervention (PCI) with abciximab therapy. The study sought to assess the relationship between the level of platelet-monocyte aggregation and increases in cardiac troponin I post coronary intervention.

Methods: Blood samples were collected from 40 patients before PCI and 10 min after abciximab administration.

Failure of current public educational campaigns to impact on the initial response of patients with possible heart attack.

Aims: The National Heart Foundation of Australia recognizes that the risk of lethal arrhythmias is greater very early after the onset of myocardial infarction and that the more promptly flow can be restored in the infarct-related artery the greater will be the benefits for survival and preservation of heart function. The Heart Foundation has therefore conducted several public media campaigns to encourage patients to seek help more promptly and evaluated their impact.

Methods: Since 1996, we have conducted four surveys of delays preceding admission of patients to coronary care units throughout Australia to assess the impact of the Heart Foundation's media campaigns.

Actinomycin-eluting stent for coronary revascularization: a randomized feasibility and safety study: the ACTION trial.

Objectives: We sought to demonstrate the safety and performance of the actinomycin D-coated Multilink-Tetra stent(Guidant Corp., Santa Clara, California) in the treatment of patients with single de novo native coronary lesions.

Background: Drug-eluting stents (DES) releasing sirolimus or paclitaxel dramatically reduce restenosis.

Five-year angiographic patency of radial artery bypass grafts.

Background: Little information exists regarding mid-term and long-term patency of radial artery grafts.

Methods And Results: We performed restudy coronary angiography at 5.2+/-0.

Patterns of coronary artery movement and the development of coronary atherosclerosis.

Mechanical stress in coronary arteries has been postulated to cause endothelial injury and atherosclerotic lesions, but the relationship between the pattern of coronary artery movement (CAM) and lesion severity is not known. In the present study CAM was classified into 10 patterns, which were grouped into 3 classes: (1) bend type = coronary artery flexes into a curve; (2) compression type = segmental length is shortened without vertical deviation of the artery; (3) displacement type = location of the coronary artery shifts without change of segmental length or shape. Assessment of CAM was made for 6 segments from the left anterior descending artery and 3-5 segments from the left circumflex artery, and in total 673 segments were analyzed.