Sealing ability of mineral trioxide aggregate and Biodentine as the root end filling material, using two different retro preparation techniques - An in vitro study

 Aim: The purpose of this study is compare sealing ability of mineral trioxide aggregate (MTA) and Biodentine as root end filling material, and also to compare the effect of different retro preparation techniques i.e. conventional bur v/s ultrasonic tips on sealing ability of both the root end filling materials. Materials and Methods: Totally, 40 extracted human single rooted teeth were decoronated, and root canal treatment was performed. Teeth were stored in saline for 1 week. Following which, root ends were apically resected at 90° angle to a long axis of the root and prepared. The samples were randomly divided into two groups of 20 specimens each. Group I: MTA, Group II: Biodentine as the root end filling. Each group was subdivided as A - round bur preparation and B - ultrasonic tip root end preparation. Samples were stored in saline for 48 h and then immersed in 0.5% rhodamine B dye for 24 h, sectioned and evaluated for leakage under confocal laser scanning microscope. Results: Statistical analysis of readings was done using factorial ANOVA. Biodentine and ultrasonic preparations showed significantly less microleakage than MTA and bur preparations. Conclusion: Biodentine can be used as a replacement for MTA, as a root end filling material

Direct regional microvascular monitoring and assessment of blood brain barrier function following cerebral ischemia-reperfusion injury

Evans Blue (EB) is often used to evaluate Blood-Brain Barrier Damage (BBB) in cerebral ischemia, frequently by dye extraction. Herein we present a method that allows assessing regional brain microvasculature, distribution of EB and Fluorescent Isothiocyanate-Labeled Red Blood Cells (FITC-RBCs) in a rat model of acute cerebral Ischemia-Reperfusion (I-R). Wistar rats were subjected to 3 h of middle cerebral artery occlusion and then reperfused. At ~2.5 h of reperfusion, BBB opening was assessed by contrast enhanced magnetic resonance imaging. It was followed by injections of EB and FITC-RBCs that circulated for either 5 or 20 min. Regional microvasculature and tracer distributions were assessed by laser scanning confocal microscopy. Microvascular networks in stroke-affected regions networks were partially damaged with apparent EB extravasation. Brain regions were affected in the following order: preoptic area (PoA)\u3estriatum (Str)\u3ecortex (Ctx). EB leakage increased with circulation time in Str. Cells around the leakage sites sequestered EB. An inverse correlation was observed between low CBF rates recorded during MCA occlusion and post-reperfusion EB extravasation patterns. Accordingly, this approach provided data on brain regional microvascular status, extravascular tracer distribution and its cellular uptake. It may be useful to evaluate model-dependent variations in vascular injury and efficacy of putative vascular protective drugs in stroke

Treatment of pulmonary exacerbations in cystic fibrosis

Purpose of review This review will discuss the challenges of defining a pulmonary exacerbations in cystic fibrosis and the key pathogens, which contribute. It will discuss the treatment options currently available and the importance of preventing pulmonary exacerbations.Recent findings The basis for treatment of pulmonary exacerbations remains unchanged over the past 15 years and whilst there have been trials exploring alternative antibiotics, there has been little change. However, there are ongoing studies that are expected to establish a platform for identifying best practices. Chronic cystic fibrosis therapies have been shown to reduce pulmonary exacerbations. In the era of new CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapies, the number of pulmonary exacerbations are expected to be even fewer. However, it is unclear whether the other chronic therapies can be discontinued without losing their benefits in reducing exacerbations.Summary Although there is no universal definition of a pulmonary exacerbation in cystic fibrosis, proposed definitions have many similarities. We have outlined the current recommendations for treatment of pulmonary exacerbations, including the duration and location of treatments. We have also summarized the key therapies used for prevention of pulmonary exacerbations in cystic fibrosis

Is verbal reference impaired in autism spectrum disorder? A systematic review

Background and aims: Pragmatic language is a key difficulty in autism spectrum disorder. One such pragmatic skill is verbal reference, which allows the current entity of shared interest between speakers to be identified and thus enables fluid conversation. The aim of this review was to determine the extent to which studies have found that verbal reference is impaired in autism spectrum disorder. We organise the review in terms of the methodology used and the modality (production versus comprehension) in which proficiency with verbal reference was assessed. Evidence for the potential cognitive underpinnings of these skills is also reviewed. Main contribution and methods: To our knowledge, this is the first systematic review of verbal reference in autism spectrum disorder. PsychINFO and Web of Science were systematically screened using the combination of search terms outlined in this paper. Twenty-four studies met our inclusion criteria. Twenty-two of these examined production, whereby the methodology ranged from elicited conversation through to elicited narrative, the ‘director’ task and other referential communication paradigms. Three studies examined reference interpretation. (One study investigated both production and appropriacy judgement). Four studies examined the relationship between appropriate usage of verbal reference and formal language (lexico-syntactic ability). Two studies investigated whether reference production related to Theory of Mind or Executive Functioning. Conclusion and implications: Across a range of elicited production tasks, the predominant finding was that children and adults with autism spectrum disorder demonstrate a deficit in the production of appropriate verbal reference in comparison not only to typically developing groups, but also to groups with Developmental Language Disorder or Down syndrome. In contrast, the studies of reference interpretation which compared performance to typical control groups all found no between-group differences in this regard. To understand this cross-modality discrepancy, we need studies withthe same sample of individuals, whereby the task requirements for comprehension and production are as closely matched as possible. The field also requires the development of experimental manipulations which allow us to pinpoint precisely if and how each comprehension and/or production task requires mentalising and/or various components of executive functioning. Only through such detailed and controlled experimental work would it be possible to determine the precise location of impairments in verbal reference in autism spectrum disorder. A better understanding of this would contribute to the development of interventions

Author Correction: Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Transplantation tolerance: lessons from experimental rodent models

Immunological tolerance or functional unresponsiveness to a transplant is arguably the only approach that is likely to provide long-term graft survival without the problems associated with life-long global immunosuppression. Over the past 50 years, rodent models have become an invaluable tool for elucidating the mechanisms of tolerance to alloantigens. Importantly, rodent models can be adapted to ensure that they reflect more accurately the immune status of human transplant recipients. More recently, the development of genetically modified mice has enabled specific insights into the cellular and molecular mechanisms that play a key role in both the induction and maintenance of tolerance to be obtained and more complex questions to be addressed. This review highlights strategies designed to induce alloantigen specific immunological unresponsiveness leading to transplantation tolerance that have been developed through the use of experimental models

A CLINICAL STUDY OF INHALANT ANAESTHESIA IN DOGS

A clinical trial was undertaken using three different inhalant anaesthetic agents and one intravenous anaesthetic agent in dogs undergoing routine desexing surgery. Healthy adult dogs undergoing either ovariohysterectomy or castration were assessed as to their demeanour, with the more excitable dogs being placed in groups receiving premedication with acepromazine and morphine. All dogs were then randomly assigned an anaesthetic agent for induction of general anaesthesia. The agents were the inhalants halothane, isoflurane and sevoflurane, and the intravenous agent propofol. Inhalant inductions were undertaken using a tight fitting mask attached to a standard anaesthetic machine with a rebreathing circuit, with the maximum dose of inhalant available from a standard vaporiser. Propofol inductions were undertaken via intravenous catheter. Dogs induced with propofol were randomly assigned one of the three inhalant agents for maintenance. Those induced by inhalant agent were maintained using the same agent. The surgical procedure was undertaken in standard fashion, as was recovery from anaesthesia. All dogs received the non-steroidal anti-inflammatory agent meloxicam. Data collection was divided into three stages: induction, maintenance, and recovery from anaesthesia. Variables measured at induction of anaesthesia were time to intubation, number of intubation attempts, tolerance of mask, quality of induction and quality of transfer to the maintenance stage. Standard variables for monitoring of anaesthesia were recorded throughout the maintenance of anaesthesia. Variables measured at recovery were time to righting, time to standing and quality of recovery. The mean time to intubation when using the newer inhalant sevoflurane (196.2 ± 14.8sec, mean ± SE) was not significantly different to that for halothane (221.4 ± 14.0sec) or isoflurane (172.4 ± 15.0sec). Time to intubation with isoflurane was significantly faster than with halothane. Mean time to intubation with propofol (85.4 ± 7.7sec) was significantly faster than that for any of the three inhalants. Choice of inhalant had no effect on quality of induction. The use of premedication significantly improved the quality of induction. The use of propofol for induction likewise significantly improved the quality of induction. Standard cardiorespiratory variables measured during the maintenance phase of anaesthesia remained within normal clinical ranges for all three inhalants, and were therefore not further analysed. Choice of inhalant agent had no significant effect on the time to righting or standing in recovery. The use of propofol for induction had no effect on these variables. Animals placed in groups receiving premedication had significantly longer times to righting and standing. The oesophageal temperature at the end of the procedure had a significant effect on times to righting and standing, with lower temperatures contributing to slower recoveries. Independent of procedure time, male dogs had shorter times to righting than female dogs

Research approvals iceberg: how a 'low-key' study in England needed 89 professionals to approve it and how we can do better.

BACKGROUND: The red tape and delays around research ethics and governance approvals frequently frustrate researchers yet, as the lesser of two evils, are largely accepted as unavoidable. Here we quantify aspects of the research ethics and governance approvals for one interview- and questionnaire-based study conducted in England which used the National Health Service (NHS) procedures and the electronic Integrated Research Application System (IRAS). We demonstrate the enormous impact of existing approvals processes on costs of studies, including opportunity costs to focus on the substantive research, and suggest directions for radical system change. MAIN TEXT: We have recorded 491 exchanges with 89 individuals involved in research ethics and governance approvals, generating 193 pages of email text excluding attachments. These are conservative estimates (e.g. only records of the research associate were used). The exchanges were conducted outside IRAS, expected to be the platform where all necessary documents are provided and questions addressed. Importantly, the figures exclude the actual work of preparing the ethics documentation (such as the ethics application, information sheets and consent forms). We propose six areas of work to enable system change: 1. Support the development of a broad range of customised research ethics and governance templates to complement generic, typically clinical trials orientated, ones; 2. Develop more sophisticated and flexible frameworks for study classification; 3. Link with associated processes for assessment, feedback, monitoring and reporting, such as ones involving funders and patient and public involvement groups; 4. Invest in a new generation IT infrastructure; 5. Enhance system capacity through increasing online reviewer participation and training; and 6. Encourage researchers to quantify the approvals processes for their studies. CONCLUSION: Ethics and governance approvals are burdensome for historical reasons and not because of the nature of the task. There are many opportunities to improve their efficiency and analytic depth in an age of innovation, increased connectivity and distributed working. If we continue to work under current systems, we are perpetuating, paradoxically, an unethical system of research approvals by virtue of its wastefulness and impoverished ethical debate

Reduced engagement with social stimuli in 6-month-old infants with later Autism Spectrum Disorder: a longitudinal prospective study of infants at high familial risk

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of the population, and close to 20% of prospectively studied infants with an older sibling with ASD. Although significant progress has been made in characterizing the emergence of behavioral symptoms of ASD, far less is known about the underlying disruptions to early learning. Recent models suggest that core aspects of the causal path to ASD may only be apparent in early infancy. Here, we investigated social attention in 6- and 12-month-old infants who did and did not meet criteria for ASD at 24 months using both cognitive and electrophysiological methods. We hypothesized that a reduction in attention engagement to faces would be associated with later ASD. Methods: In a prospective longitudinal design, we used measures of both visual attention (habituation) and brain function (event-related potentials to faces and objects) at 6 and 12 months, and investigated the relationship to ASD outcome at 24 months. Results: High-risk infants who met criteria for ASD at 24 months showed shorter epochs of visual attention, faster but less prolonged neural activation to faces, and delayed sensitization responses (increases in looking) to faces at 6 months; these differences were less apparent at 12 months. These findings are consistent with disrupted engagement of sustained attention to social stimuli. Conclusions: These findings suggest that there may be fundamental early disruptions to attention engagement that may have cascading consequences for later social functioning