Characterisation and microleakage of a new hydrophilic fissure sealant – UltraSeal XT® hydro™

Objectives: The new hydrophilic fissure sealant, UltraSeal XT® hydro™ (Ultradent Products, USA), was characterised and its in vitro resistance to microleakage after placement on conventionally acid etched and sequentially lased and acid etched molars was investigated. Materials and Methods: The sealant was characterised by Fourier transform infra-red spectroscopy, (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX) and Vickers indentation test. Occlusal surfaces of extracted human molars were either conventionally acid etched (n = 10), or sequentially acid etched and laser irradiated (n = 10). UltraSeal XT® hydro™ was applied to both groups of teeth which were then subjected to 2500 thermocycles between 5 and 55 °C prior to microleakage assessment by fuchsin dye penetration. Results: UltraSeal XT® hydro™ is an acrylate-based sealant which achieved a degree of conversion of 50.6 ± 2.2% and a Vickers microhardness of 24.2 ± 1.5 under standard light curing (1000 mWcm-2 for 20 s). Fluoride ion release was negligible within a 14-day period. SEM and EDX analyses indicated that the sealant comprises irregular sub-micron and nano-sized silicon-, barium- and aluminium-bearing filler phases embedded within a ductile matrix. Laser preconditioning was found to significantly reduce microleakage (Mann-Whitney U test, p < 0.001). The lased teeth presented enhanced surface roughness on a 50 to 100 μm scale which caused the segregation and concentration of the filler particles at the enamel-sealant interface. Conclusion: Laser preconditioning significantly decreased microleakage and increased enamel surface roughness which caused zoning of the filler particles at the enamel-sealant interface

Effect of Er:YAG laser enamel conditioning and moisture on the microleakage of a hydrophilic sealant

For a given sealant, successful pit and fissure sealing is principally governed by the enamel conditioning technique and the presence of moisture contamination. A new generation of hydrophilic resin sealants is reported to tolerate moisture. This study investigates the impact of Er:YAG laser pre-conditioning and moisture contamination on the microleakage of a recent hydrophilic sealant. Occlusal surfaces of extracted human molars were either acid etched (n = 30), or successively lased and acid etched (n = 30). Ten teeth from each group were either air-dried, water-contaminated, or saliva-contaminated prior to sealing with UltraSeal XT® hydro™. Samples were inspected for penetration of fuchsin dye following 3000 thermocycles between 5 and 50 °C, and the enamel–sealant interfaces were observed by scanning electron microscopy (SEM). Significant differences in microleakage were evaluated using the Mann–Whitney U test with Bonferroni adjustment (p = 0.05). Laser pre-conditioning significantly reduced dye penetration irrespective of whether the enamel surface was moist or dry. Microleakageof water-contaminated acid etched teeth was significantly greater than that of their air-dried or saliva-contaminated counterparts. SEM analysis demonstrated good adaptation in all groups with the exception of water-contaminated acid etched teeth which exhibited relatively wide gaps. In conclusion, this hydrophilic sealant tolerates the presence of saliva, although water was found to impair its sealing ability. Laser pre-conditioning significantly decreases microleakage in all cases

The impact of Er:YAG laser enamel conditioning on the microleakage of a new hydrophilic sealant — UltraSeal XT® hydro™

UltraSeal XT® hydro™ is a new hydrophilic, light-cured, methacrylate-based pit and fissure sealant which has been developed by Ultradent Products, USA. The sealant is highly filled with a 53 wt.% mixture of inorganic particles which confer both thixotropy and radiopacity. The principal purpose of this study was to investigate the microleakage of UltraSeal XT® hydro™ as a function of different enamel etching techniques. The occlusal surfaces of sound, extracted human molars were either acid etched, Er:YAG laser irradiated or successively laser irradiated and acid etched. UltraSeal XT® hydro™ was applied to each group of teeth (n=10) which were subjected to a thermocycling process consisting of 2500 cycles between 5 and 50°C with a dwell time of 30s. Microleakage assessments were then carried out using 0.5 % fuchsin dye and optical microscopy. The microleakage score data were analysed using the Kruskal-Wallis, Mann–Whitney U test with Bonferroni adjustment. No significant differences in microleakage were noted between the individually acid etched and laser-irradiated groups (p>0.05); however, teeth treated with a combination of laser irradiation and acid etching demonstrated significantly lower microleakage scores (p<0.001). Electron microscopy with energy-dispersive X-ray analysis revealed that the mineral filler component of UltraSeal XT® hydro™ essentially comprises micrometre-sized particles of inorganic silicon-, aluminium- and barium-bearing phases. Laser etching increases the roughness of the enamel surface which causes a concentrated zoning of the filler particles at the enamel-sealant interface

Pneumocystis murina colonization in immunocompetent surfactant protein A deficient mice following environmental exposure

<p>Abstract</p> <p>Background</p> <p><it>Pneumocystis spp</it>. are opportunistic pathogens that cause pneumonia in immunocompromised humans and animals. <it>Pneumocystis </it>colonization has also been detected in immunocompetent hosts and may exacerbate other pulmonary diseases. Surfactant protein A (SP-A) is an innate host defense molecule and plays a role in the host response to <it>Pneumocystis</it>.</p> <p>Methods</p> <p>To analyze the role of SP-A in protecting the immunocompetent host from <it>Pneumocystis </it>colonization, the susceptibility of immunocompetent mice deficient in SP-A (KO) and wild-type (WT) mice to <it>P. murina </it>colonization was analyzed by reverse-transcriptase quantitative PCR (qPCR) and serum antibodies were measured by enzyme-linked immunosorbent assay (ELISA).</p> <p>Results</p> <p>Detection of <it>P. murina </it>specific serum antibodies in immunocompetent WT and KO mice indicated that the both strains of mice had been exposed to <it>P. murina </it>within the animal facility. However, P. <it>murina </it>mRNA was only detected by qPCR in the lungs of the KO mice. The incidence and level of the mRNA expression peaked at 8–10 weeks and declined to undetectable levels by 16–18 weeks. When the mice were immunosuppressed, <it>P. murina </it>cyst forms were also only detected in KO mice. <it>P. murina </it>mRNA was detected in <it>SCID </it>mice that had been exposed to KO mice, demonstrating that the immunocompetent KO mice are capable of transmitting the infection to immunodeficient mice. The pulmonary cellular response appeared to be responsible for the clearance of the colonization. More CD4+ and CD8+ T-cells were recovered from the lungs of immunocompetent KO mice than from WT mice, and the colonization in KO mice depleted CD4+ cells was not cleared.</p> <p>Conclusion</p> <p>These data support an important role for SP-A in protecting the immunocompetent host from <it>P. murina </it>colonization, and provide a model to study <it>Pneumocystis </it>colonization acquired via environmental exposure in humans. The results also illustrate the difficulties in keeping mice from exposure to <it>P. murina </it>even when housed under barrier conditions.</p

Group mindfulness based cognitive therapy vs group support for self-injury among young people: Study protocol for a randomised controlled trial

Background: Non-suicidal self-injury (NSSI) is a transdiagnostic behaviour that can be difficult to treat; to date no evidence based treatment for NSSI exists. Mindfulness Based Cognitive Therapy (MBCT) specifically targets the mechanisms thought to initiate and maintain NSSI, and thus appears a viable treatment option. The aims of the current study are to test the ability of MBCT to reduce the frequency and medical severity of NSSI, and explore the mechanisms by which MBCT exerts its effect. Methods/Design: We will conduct a parallel group randomised controlled trial of Mindfulness Based Cognitive Therapy (MBCT) versus Supportive Therapy (ST) in young people aged 18-25 years. Computerised block randomisation will be used to allocate participants to groups. All participants will meet the proposed DSM-5 criteria for NSSI (i.e. five episodes in the last twelve months). Participants will be excluded if they: 1) are currently receiving psychological treatment, 2) have attempted suicide in the previous 12 months, 3) exhibit acute psychosis, 4) have a diagnosis of borderline personality disorder, or 5) have prior experience of MBCT. Our primary outcome is the frequency and medical severity of NSSI. As secondary outcomes we will assess changes in rumination, mindfulness, emotion regulation, distress tolerance, stress, and attentional bias, and test these as mechanisms of change. Discussion: This is the first randomised controlled trial to test the efficacy of MBCT in reducing NSSI. Evidence of the efficacy of MBCT for self-injury will allow provision of a brief intervention for self-injury that can be implemented as a stand-alone treatment or integrated with existing treatments for psychiatric disorders

Three-Wall Segment (TriSeg) Model Describing Mechanics and Hemodynamics of Ventricular Interaction

A mathematical model (TriSeg model) of ventricular mechanics incorporating mechanical interaction of the left and right ventricular free walls and the interventricular septum is presented. Global left and right ventricular pump mechanics were related to representative myofiber mechanics in the three ventricular walls, satisfying the principle of conservation of energy. The walls were mechanically coupled satisfying tensile force equilibrium in the junction. Wall sizes and masses were rendered by adaptation to normalize mechanical myofiber load to physiological standard levels. The TriSeg model was implemented in the previously published lumped closed-loop CircAdapt model of heart and circulation. Simulation results of cardiac mechanics and hemodynamics during normal ventricular loading, acute pulmonary hypertension, and chronic pulmonary hypertension (including load adaptation) agreed with clinical data as obtained in healthy volunteers and pulmonary hypertension patients. In chronic pulmonary hypertension, the model predicted right ventricular free wall hypertrophy, increased systolic pulmonary flow acceleration, and increased right ventricular isovolumic contraction and relaxation times. Furthermore, septal curvature decreased linearly with its transmural pressure difference. In conclusion, the TriSeg model enables realistic simulation of ventricular mechanics including interaction between left and right ventricular pump mechanics, dynamics of septal geometry, and myofiber mechanics in the three ventricular walls

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces

Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases

The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (A?). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer’s disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that A? is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of A? in the glia limitans in Alzheimer’s disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of A?. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012

OBJECTIVE: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. DESIGN: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. RESULTS: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). CONCLUSIONS: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients