Orthodontic apps: an assessment of quality (using the Mobile App Rating Scale (MARS)) and behaviour change techniques (BCTs).

BACKGROUND: Apps have been shown to be an effective tool in changing patients' behaviours in orthodontics and can be used to improve their compliance with treatment. The Behaviour Change Techniques (BCTs) and quality (using MARS) within these apps have previously not been published. OBJECTIVES: 1. To evaluate the quality of these apps aiming to change behaviour. 2. To assess BCTs used in patient focused orthodontic apps. METHODS: The UK Google Play and Apple App Stores were searched to identify all orthodontic apps and 305 apps were identified. All 305 apps were assessed for the presence of BCTs using an accepted taxonomy of BCTs (Behaviour Change Wheel (BCW)), widely utilised in healthcare. Of those containing BCTs, the quality was assessed using the Mobile App Rating Scale (MARS), a validated and multi-dimensional tool which rates apps according to 19 objective criteria. Data collection was carried out by two calibrated, independent assessors and repeated after 6 weeks for 25% of the apps by both assessors. RESULTS: BCTs were found in 31 apps, although only 18 of them were analysed for quality and 13 apps were excluded. Six different BCTs were identified: these were most commonly 'prompts/cues', and 'information about health consequences'. All apps were shown to be of moderate quality (range 3.1-3.7/5). Inter-rater and intra-rater reliability for BCT and quality assessment were excellent. CONCLUSIONS: The current availability of orthodontic apps of sufficient quality to recommend to patients is very limited. There is therefore a need for high-quality orthodontic apps with appropriate BCTs to be created, which may be utilised to improve patients' compliance with treatment.

Population Data Centre Profile - The Western Australian Data Linkage Branch.

Established in 1995, the Western Australian Data Linkage Branch (DLB) is Australia's longest running data linkage agency. The Western Australian Data Linkage System (WADLS) employs an enduring linkage model spanning over 60 data collections supported by internally developed and supported software and IT infrastructure. DLB has delivered, and continues to deliver, a range of significant data linkage innovations, many of which have been adopted elsewhere. A current restructure within the Western Australian Department of Health (which we will refer to as the Department of Health) will provide an improved funding model geared toward addressing issues with staff retention, capacity and customer service, as well as fostering improvements to data management, governance and availability. Research using linked data provided by DLB has been used in over 800 projects resulting in over 2350 publications and outcomes for policy development, service delivery and public health. Demand continues to grow for data linkage services and with the Department of Health's bolstered commitment to resourcing, DLB looks forward to a future for data linkage in Western Australia that is sustainable, high quality, efficient, and safe.

The role of core needle biopsies in the management of neck lumps.

INTRODUCTION: King's College Hospital has proudly provided a one-stop neck lump clinic since 2012. These multidisciplinary clinics allow for rapid diagnoses due to in-clinic investigations. In April 2013, ultrasound-guided core needle biopsies were introduced as an alternative/adjunct to fine-needle aspiration cytology and open biopsies for obtaining histological diagnoses. The aim of the study was to assess the impact of core needle biopsies on the diagnosis of neck lumps compared with fine-needle aspiration cytology and open biopsies between April 2015 and May 2016. MATERIALS AND METHODS: Data were collected prospectively between April 2015 and May 2016 and analysed for numbers of fine-needle aspiration cytology, core needle biopsies and open biopsies performed and diagnoses made. RESULTS: A total of 190 patients were seen on the clinic; 51 had fine-needle aspiration cytology and 19 procedures gave a diagnosis. Of the remainder of these patients, 21 went on to have a core needle biopsy and 12 biopsies gave a diagnosis. An additional eight patients only had a core needle biopsy, of which five biopsies gave a diagnosis. Of the ten patients who had an open biopsy, four had a previous fine-needle aspiration cytology and core needle biopsy, three only a core needle biopsy, two had neither and one had fine-needle aspiration cytology. CONCLUSION: The introduction of core needle biopsies has reduced the number of open biopsies performed. With increasing acceptance of this minimally invasive technique, core needle biopsies appear to be forming the key diagnostic investigation in patients with neck lumps.

The α5-GABAAR inverse agonist MRK-016 upregulates hippocampal BDNF expression and prevents cognitive deficits in LPS-treated mice, despite elevations in hippocampal Aß.

Alzheimer's disease is marked by the presence of amyloid-beta (Aß) plaques, elevated central cytokine levels, dysregulation of BDNF-related gene expression, and cognitive decline. Previously, our laboratory has demonstrated that repeated administration of peripheral LPS is sufficient to significantly increase the presence of central Aß in the hippocampus, and that this upregulation corresponds with deficits in learning and memory. We have also previously demonstrated that the inverse benzodiazepine agonist MRK-016 (MRK) can protect against memory acquisition and consolidation errors in mice. To extend these findings, the current study explored the protective effects of MRK in the context of LPS-induced hippocampal Aß accumulation. Hippocampal Aß was significantly elevated, relative to saline-treated animals, following seven days of peripheral LPS injections. Animals were then trained in a contextual fear conditioning paradigm and were immediately treated with MRK or saline once training was complete. Behavioral testing occurred the day after training. Results from this study demonstrate that repeated injections of LPS significantly elevate hippocampal Aß, and inhibit acquisition of contextual fear. Post-training treatment with MRK restored behavioral expression of fear in LPS-treated animals, despite elevated hippocampal Aß, an effect that may be attributed to increased BDNF mRNA expression. Therefore, our data indicate that MRK can prevent LPS- induced cognitive deficits associated with elevated Aß, and restore hippocampal BDNF expression.

Effect of obesity and type 2 diabetes, and glucose ingestion on circulating spexin concentration in adolescents.

Spexin is a novel peptide that has been reported to be down regulated in obese adults and children and in normoglycemic adults following glucose ingestion. Spexin may therefore have a role in metabolic regulation. The purpose of the current study was to determine the effect of obesity and type 2 diabetes (T2DM), and the effect of glucose ingestion on circulating spexin concentration in adolescents. Boys and girls (mean age 16 years old) classified as healthy normal weight (NW, n = 22), obese (Ob, n = 10), or obese with T2DM (n = 12) completed measurements of body composition, blood pressure, cardiorespiratory fitness, and blood concentrations of glucose, insulin, and lipids. The median fasting serum spexin concentration did not differ between groups (NW: 0.35; Ob: 0.38, T2DM: 0.34 ng/mL, respectively). In 10 NW participants who completed a standard oral glucose tolerance test, spexin concentration was unchanged at 30 and 120 minutes relative to the fasting baseline. Finally, spexin was not significantly correlated with any of the body composition, fitness, or blood biochemical measurements. These data do not support the proposed role of spexin as a metabolic regulator or biomarker of glucose control in adolescents.

Career satisfaction and work-life balance of specialist orthodontists within the UK/ROI.

Objectives To investigate factors affecting career satisfaction and work-life balance in specialist orthodontists in the UK/ROI.Design and setting Prospective questionnaire-based study.Subjects and methods The questionnaire was sent to specialist orthodontists who were members of the British Orthodontic Society.Results Orthodontists reported high levels of career satisfaction (median score 90/100). Career satisfaction was significantly higher in those who exhibited: i) satisfaction with working hours; ii) satisfaction with the level of control over their working day; iii) ability to manage unexpected home events; and iv) confidence in how readily they managed patient expectations. The work-life balance score was lower than the career satisfaction score but the median score was 75/100. Work-life balance scores were significantly affected by the same four factors, but additionally were higher in those who worked part-time.Conclusions Orthodontists in this study were highly satisfied with their career and the majority responded that they would choose orthodontics again. Work-life balance scores were lower than career satisfaction scores but still relatively high. It is important for the profession to consider ways of maintaining, or improving, career satisfaction and work-life balance; including maintaining flexibility of working hours and ensuring that all clinicians have ready access to appropriate training courses throughout their careers (for example, management of patient expectations).

Decomposition, nitrogen and carbon mineralization from food and cover crop residues in the central plateau of Haiti.

Cover crops are a major focus of conservation agriculture efforts because they can provide soil cover and increase nutrient availability after their mineralization in cropping systems. To evaluate the effect of residue type and placement on rate of decomposition and carbon (C) and nitrogen (N) mineralization, residues from two food crops, maize (Zea mays L.) and common bean (Phaseolus vulgaris L.), and two promising cover crops, sunn hemp (Crotalaria juncea L.) and sorghum sudangrass (Sorghum bicolor [L.] Moench x S. bicolor var. Sudanese [Piper] Stapf) were used in a litterbag study in the Central Plateau region of Haiti from May to September, 2013. Residues were placed in litterbags at a rate equivalent to 3.25 Mg residue ha(-1) either on the soil surface or buried at 15 cm to represent a tilled and no-tillage system, respectively. Initial C:N ratios were: maize > common bean > sorghum sudangrass > sunn hemp. Highest residue mass loss rates and C and N mineralization generally occurred in the reverse order. Overall, surface-placed residues decomposed more slowly with 40 and 17 % of initial residue mass of surface and buried residues, respectively, remaining at 112 days. Carbon and N mineralization was higher when residues were buried. Net N mineralization of buried residues was 0.12, 0.07, 0.06, and 0.03 g N g residue(-1) for sunn hemp, sorghum sudangrass, maize, and common bean, respectively over 112 days. To achieve the goal of increasing nutrient supply while maintaining year-round cover, a combination of grass and legume cover crops may be required with benefits increasing over multiple seasons.

Pre-treatment of C57BL6/J mice with the TLR4 agonist monophosphoryl lipid A prevents LPS-induced sickness behaviors and elevations in dorsal hippocampus interleukin-1ß, independent of interleukin-4 expression.

Peripheral administration of lipopolysaccharide (LPS) elevates production of pro-inflammatory cytokines, and motivates the expression of sickness behaviors. In this study, we tested the ability of an LPS-derived adjuvant, monophosphoryl lipid A (MPLA), to prevent LPS-induced sickness behaviors in a burrowing paradigm. Testing occurred over a three-day period. Animals received a single injection of either MPLA or saline the first two days of testing. On day three, animals received either LPS or saline. Tissue from the dorsal hippocampus was collected for qRT-PCR to assess expression of IL-1ß and IL-4. Results indicate that, during the pre-treatment phase, administration of MPLA induces an immune response sufficient to trigger sickness behaviors. However, we observed that animals pre-treated with MPLA for two days were resistant to LPS-induced sickness behaviors on day three. Results from the qRT-PCR analysis indicated that LPS-treated animals pre-treated with MPLA expressed significantly less IL-1ß compared to LPS-treated animals pre-treated with saline. However, we did not observe a significant difference in IL-4 expression between groups. Therefore, results indicate that under the given parameters of the study, MPLA pre-treatment protects against LPS-induced sickness behaviors, at least in part, by decreasing expression of the pro-inflammatory cytokine IL-1ß.

Administration of the inverse benzodiazepine agonist MRK-016 rescues acquisition and memory consolidation following peripheral administration of bacterial endotoxin.

Recent evidence suggests that inflammation-induced decrements in cognitive function can be mitigated via manipulation of excitatory or inhibitory transmission. We tested the ability of the inverse benzodiazepine agonist, MRK-016 (MRK) to protect against LPS-induced deficits in memory acquisition and consolidation, using a contextual fear conditioning (CFC) paradigm. In Experiment One, mice received lipopolysaccharide (LPS) and/or MRK injections prior to CFC training, and were then tested 24h after training. In Experiment Two, animals received similar treatment injections immediately after training, and were tested 24h later. Additionally, hippocampal samples were collected 4h after LPS injections and immediately after testing, to evaluate brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) mRNA expression. Results indicate that MRK can protect against LPS-induced learning/memory decrements in both paradigms. We also found, in both paradigms, that animals treated with LPS/Saline expressed significantly less BDNF mRNA when compared to Saline/Saline-treated animals 4h after LPS administration, but that MRK did not restore BDNF expression levels. Further, treatment administrations had no effect on IGF-1 mRNA expression at any collection time-point. In summary, MRK-016 can protect against LPS-induced deficits in memory acquisition and consolidation, in this hippocampus-dependent paradigm, though this protection occurs independently of recovery of BDNF expression.

Gene flow between nascent species: geographic, genotypic and phenotypic differentiation within and between Aquilegia formosa and A. pubescens.

Speciation can be described as a reduction, and the eventual cessation, in the ability to interbreed. Thus, determining how gene flow differs within and between nascent species can illuminate the relative stage the taxa have attained in the speciation process. Aquilegia formosa and A. pubescens are fully intercompatible, yet occur in different habitats and have flowers specialized for pollination by hummingbirds and hawkmoths, respectively. Using 79 SNP loci, we genotyped nearly 1000 individuals from populations of both species in close proximity to each other and from putative hybrid zones. The species shared all but one SNP polymorphism, and on average, allele frequencies differed by only 0.14. However, the species were clearly differentiated using Structure, and admixed individuals were primarily identified at putative hybrid zones. PopGraph identified a highly integrated network among all populations, but populations of each species and hybrid zones occupied distinct regions in the network. Using either conditional graph distance (cGD) or Fst/(1-Fst), we found significant isolation by distance (IBD) among populations. Within species, IBD was strong, indicating high historic gene flow. IBD extended approximately 100 km in A. pubescens and 30 km in A. formosa. However, IBD between the species was very weak and extended only a few km beyond hybrid zones, suggesting little recent gene flow. The extensive sharing of SNP polymorphisms between these species suggests that they are very early in the speciation process while the low signal of IBD suggests that they have largely ceased gene exchange.

Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer.

Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were down-regulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results and our previous studies suggest that ZIP4 is the only zinc transporter that is significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might serve as a novel molecular target for pancreatic cancer diagnosis and therapy.

Genomic sequencing of key genes in mouse pancreatic cancer cells.

Pancreatic cancer is a multiple genetic disorder with many mutations identified during the progression. Two mouse pancreatic cancer cell lines were established which showed different phenotype in vivo: a non-metastatic cell line, Panc02, and a highly metastatic cell line, Panc02-H7, a derivative of Panc02. In order to investigate whether the genetic mutations of key genes in pancreatic cancer such as KRAS, TP53 (p53), CDKN2A (p16), SMAD4, ZIP4, and PDX-1 contribute to the phenotypic difference of these two mouse pancreatic cancer cells, we sequenced the exonic regions of these key genes in both cell lines and in the normal syngeneic mouse pancreas and compared them with the reference mouse genome sequence. The exons of KRAS, SMAD4, CDKN2A (p16), TP53 (p53), ZIP4, and PDX-1 genes were amplified and the genotype of these genes was determined by Sanger sequencing. The sequences were analyzed with Sequencher software. A mutation in SMAD4 was identified in both cell lines. This homozygote G to T mutation in the first position of codon 174 (GAA) generated a stop codon resulting in the translation of a truncated protein. Further functional analysis indicates that different TGF-ß/SMAD signaling pathways were involved in those two mouse cell lines, which may explain the phonotypic difference between the two cells. A single nucleotide polymorphism (SNP) in KRAS gene (TAT to TAC at codon 32) was also identified in the normal pancreas DNA of the syngenic mouse and in both derived tumoral Panc02 and Panc02-H7 cells. No mutation or SNP was found in CDKN2A (p16), TP53 (p53), ZIP4, and PDX-1 genes in these two cell lines. The absence of mutations in genes such as KRAS, TP53, and CDKN2A, which are considered as key genes in the development of human pancreatic cancer suggests that SMAD4 might play a central and decisive role in mouse pancreatic cancer. These results also suggest that other mechanisms are involved in the substantial phenotypic difference between these two mouse pancreatic cancer cell lines. Further studies are warranted to elucidate the molecular pathways that lead to the aggressive metastatic potential of Panc02-H7.

Cytokines and angiogenic factors in patients with metastatic renal cell carcinoma treated with interferon-alpha: association of pretreatment serum levels with survival.

BACKGROUND: To correlate serum cytokine and angiogenic factor (CAF) levels with overall survival (OS) in metastatic renal cell carcinoma (mRCC) treated with interferon-alpha (IFN-alpha). PATIENTS AND METHODS: Serum CAF levels were measured in 103 patients treated on a randomized trial with IFN-alpha 0.5 million units (MU) twice daily or 5 MU daily. Concentrations of 17 analytes were determined by multiplex bead immunoassays [vascular endothelial growth factor A (VEGF(A)) and several cytokines] or enzyme-linked immunosorbent assay (basic fibroblast growth factor). We used proportional hazards models to evaluate the effect of CAF levels and clinical factors on OS. RESULTS: Pretreatment serum interleukin (IL) 5, IL-12 p40, VEGF(A), and IL-6 levels and Memorial Sloan-Kettering Cancer Center risk grouping independently correlated with OS, with hazard ratios of 2.33, 2.00, 2.07, 1.82, and 0.39, respectively (concordance index = 0.69 for the combined model versus 0.60 for the CAF model versus 0.52 for the clinical model). Based on an index derived from these five risk factors (RFs), patients with 0-2 RF had a median OS time of 32 months versus 9 months for patients with 3-5 RF (P < 0.0001). CONCLUSIONS: Serum CAF profiling contributes to prognostic evaluation in mRCC and helps to identify a subset of patients with 20% 5-year OS.

The neural basis of effective memory therapy in a patient with limbic encephalitis.

BACKGROUND: An fMRI study is described in which a postencephalitic woman with amnesia used a wearable camera which takes photographs passively, without user intervention, to record and review recent autobiographical events. "SenseCam" generates hundreds of images which can subsequently be reviewed quickly or one by one. RESULTS: Memory for a significant event was improved substantially when tested after 4.5 weeks, if the patient viewed SenseCam images of the event every 2 days for 3 weeks. In contrast, after only 3.5 weeks, her memory was at chance levels for a similarly significant event which was reviewed equally often, but using a written diary. During the fMRI scan, the patient viewed images of these two events, plus images of an unrehearsed event and images from a novel "control" event that she had never experienced. There was no difference in behavioural responses or in activation when the unrehearsed and novel conditions were compared. Relative to the written-rehearsed condition, successful recognition of the images in the SenseCam-rehearsed condition was associated with activation of frontal and posterior cortical regions associated with normal episodic memory. CONCLUSION: SenseCam images may provide powerful cues that trigger the recall and consolidation of stored but inaccessible memories.

Reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase γ (POLG1).

We report the case of a 2-year-old boy with seizures who developed hepatic failure shortly after commencing sodium valproate. Unexpectedly, liver function returned to normal on stopping the drug. Sequencing of the mitochondrial polymerase γ gene (POLG1) revealed four heterozygous substitutions, two of which have been identified in cases of Alpers-Huttenlocher disease.

Reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase gamma (POLG1).

We report the case of a 2-year-old boy with seizures who developed hepatic failure shortly after commencing sodium valproate. Unexpectedly, liver function returned to normal on stopping the drug. Sequencing of the mitochondrial polymerase gamma gene (POLG1) revealed four heterozygous substitutions, two of which have been identified in cases of Alpers-Huttenlocher disease.

Paediatric anaesthesia in developing countries.

Each year millions of children undergo surgery in the developing world with inadequate facilities, equipment and drugs. In many hospitals, anaesthesia is largely dependent on the availability of ketamine. Application of well-established clinical techniques, particularly for postoperative pain control, would relieve unnecessary suffering in children. Improvements in peri-operative care are required by investment in health systems and training.

Diet modification to reduce phosphorus surpluses: a mass balance approach.

Diet modification to reduce phosphorus (P) concentrations in manures has been developed in response to environmental concerns over P losses from animal agriculture to surface waters. We used USDA-NASS statistics on animal numbers and crop production to calculate county scale mass balances for manure P production, P removed in harvested portion of crops, and the potential effects of diet modification. Although spreading manure evenly over all crop acreage within a county is unlikely to occur, these calculations give a good indication as to the impact diet modification to reduce P can have at a regional or national scale. There was a high degree of regional variability in manure P surpluses (e.g., with the large crop acreages in the grain belt leading to large P offtake in crops preventing most P surpluses). In 89% of counties, there was a deficit of manure P relative to crop P removal; therefore there was a manure P surplus in 11% of counties. Diet modification decreased the percentage of states with a manure P surplus from 11 to 8%, a decrease of approximately 27%. Diet modification decreased the percentage of counties with the greatest surpluses of manure P (>30 kg ha(-1)) from 3% of all counties to 1%. Diet modification to decrease manure P is an important part of strategies to alleviate environmental concerns associated with surplus manure P in many areas, but additional strategies to deal with manure P surpluses are needed in some areas.