Can oral infection be a risk factor for Alzheimer’s disease?

Alzheimer’s disease (AD) is a scourge of longevity that will drain enormous resources from public health budgets in the future. Currently, there is no diagnostic biomarker and/or treatment for this most common form of dementia in humans. AD can be of early familial-onset or sporadic with a late-onset. Apart from the two main hallmarks, amyloid-beta and neurofibrillary tangles, inflammation is a characteristic feature of AD neuropathology. Inflammation may be caused by a local central nervous system insult and/or by peripheral infections. Numerous microorganisms are suspected in AD brains ranging from bacteria (mainly oral and non-oral Treponema species), viruses (Herpes simplex type I) and yeasts (Candida species). A causal relationship between periodontal pathogens/non-oral Treponema species of bacteria has been proposed via the amyloid-beta and inflammatory links. Periodontitis constitutes a peripheral oral infection that can provide the brain with intact bacteria and virulence factors and inflammatory mediators due to daily, transient bacteraemias. If and when genetic risk factors meet environmental risk factors in the brain, disease is expressed, in which neurocognition may be impacted, leading to the development of dementia. To achieve the goal of finding a diagnostic biomarker and possible prophylactic treatment for AD, there is an initial need to solve the etiological puzzle contributing to its pathogenesis. This review therefore addresses oral infection as the plausible aetiology of late onset AD (LOAD)

Tracking Triploid Mortalities Of Eastern Oysters Crassostrea virginica In The Virginia Portion Of The Chesapeake Bay

Since 2012, aquacultured eastern oysters Crassostrea virginica have been reported by oyster farmers to display mortality approaching 30%, and in some cases 85%, in areas of the lower Chesapeake Bay, VA. Based on accounts from industry, this mortality has typically affected 1-y-old oysters between May and early July, and has tended to occur in triploid oysters, which represent the vast bulk of production in the area. During this period, samples submitted for pathology have not revealed the presence of major pathogens as a cause. In 2015, to gain deeper insight into this mortality and determine whether specific sites, ploidy condition, or genetic lines were affected, oyster seed commercially produced in early 2014 were obtained from four lines, one diploid (2N DEBY) and three triploid (3N DEBY, 3N hANA, and 3N Northern). These lines were deployed in July 2014 at aquaculture farms at five Chesapeake Bay locations: Locklies Creek and Milford Haven on the western shore, and Pungoteague Creek, Nassawadox Creek, and Cherrystone Creek on the Eastern Shore. During this study, mortality was observed to peak in June at most sites, reaching a mean mortality across all tested lines of 17.0% and a cumulative mortality for the study period of 32.0% at Nassawadox Creek, the site most severely affected by mortality that followed the expected early summer mortality pattern. Interval mortality at all sites decreased to under 5% after June, but cumulative levels for the study period reached from 8.8% to 18.6% even at the sites least affected by mortality. This represents a high level of mortality given the documented absence of material involvement by major oyster pathogens such as Hapolosporidium nelsoni and Perkinsus marinus. Infiltration of gill tissues by hemocytes, observed in up to 33% of individuals at Nassawadox Creek coincident with the increase in mortality, was the only pathology observed. Harmful algal blooms were not associated with the mortality, nor were abnormal temperatures or salinities. There was no clear relationship of mortality to oyster genetic heritage, although there was variability in susceptibility among oyster lines and interactions between lines and specific sites. At some locations and in comparison with diploids, triploid oysters appeared to be more susceptible to mortality. Mortality in triploids was coincident with the timing of peak gametogenic development in diploids. Given the lack of involvement by major pathogens and the possible association of mortality with oyster gametogenesis, future work should seek to better understand the suite of environmental stressors potentially impacting cultured oysters in these systems and their interactions with the physiology and energetics of these animals

First direct observation of the Van Hove singularity in the tunneling spectra of cuprates

In two-dimensional lattices the electronic levels are unevenly spaced, and the density of states (DOS) displays a logarithmic divergence known as the Van Hove singularity (VHS). This is the case in particular for the layered cuprate superconductors. The scanning tunneling microscope (STM) probes the DOS, and is therefore the ideal tool to observe the VHS. No STM study of cuprate superconductors has reported such an observation so far giving rise to a debate about the possibility of observing directly the normal state DOS in the tunneling spectra. In this study, we show for the first time that the VHS is unambiguously observed in STM measurements performed on the cuprate Bi-2201. Beside closing the debate, our analysis proves the presence of the pseudogap in the overdoped side of the phase diagram of Bi-2201 and discredits the scenario of the pseudogap phase crossing the superconducting dome.Comment: 4 pages, 4 figure

Detection of toxins and harmful algal bloom cells in shellfish hatcheries and efforts toward removal

As the start of the supply chain for the aquaculture industry, hatcheries are a crucial component in the success of oyster and northern quahog (hard clam) aquaculture on the East Coast of the US. Intermittent failures in hatchery production slow industry growth and reduce profits. To begin investigations into the possible role of algal toxins in hatchery production failure, post-treatment hatchery water from one research and four commercial hatcheries in lower Chesapeake Bay, USA, was sampled for (1) toxin presence and (2) harmful algal bloom (HAB) cell enumeration. Overall, seven toxin classes, likely produced by six different HAB species, were detected in post- treatment hatchery water, despite a lack of visually identifiable HAB cells within the facility. Toxins detected include pectenotoxin-2, goniodomin A, karlotoxin-1 and karlotoxin-3, okadaic acid and dinophysistoxin-1, azaspiracid-1 and azaspiracid-2, brevetoxin-2, and microcystin-LR. In a second, more targeted study, two batches of source water were followed and sampled at each step of a water-treatment process in the VIMS Aquaculture Genetics and Breeding Technology Center research hatchery in Gloucester Point, Virginia, USA. Two treatment steps showed particular promise for decreasing the concentrations of the three toxins detected in the source water, 24-h circulation through sand filters and activated charcoal filtration. Toxin concentrations of pectenotoxin-2, 3.53 ± 0.56 pg m

Ambient vibration testing and operational modal analysis of monopole telecoms structures

This is the final version. Available on open access from Springer via the DOI in this recordA structural health monitoring (SHM) system was developed to study the ambient response of monopole communication structures in the UK operated by Arqiva Ltd. The exercise had several purposes that included the evaluation of the SHM system itself and the system identification procedures applied to the data, followed by analysis of the evaluated modal properties to validate the current analytical models, structural assessments and standardised design procedures advising on dynamics actions. This paper describes the instrumentation and procedures used during monitoring of a lightweight flexible 14.5 m tubular tapered monopole supporting an array of mobile telecoms antennas. A Bayesian OMA (BAYOMA) approach is implemented to identify structural modal properties under different time windows as comparison for further assessments. Results from stochastic subspace identification are also obtained and compared. The correlation between modal properties and monitoring wind-response data reveals specific tendencies such as nonlinear stiffness behaviour, the existence of aerodynamic damping and typical directionality of the mode shapes with future implications for reformulation of current methods of assessing dynamics on monopole

Endothelial MAPKs Direct ICAM-1 Signaling to Divergent Inflammatory Functions.

Lymphocyte transendothelial migration (TEM) is critically dependent on intraendothelial signaling triggered by adhesion to ICAM-1. Here we show that endothelial MAPKs ERK, p38, and JNK mediate diapedesis-related and diapedesis-unrelated functions of ICAM-1 in cerebral and dermal microvascular endothelial cells (MVECs). All three MAPKs were activated by ICAM-1 engagement, either through lymphocyte adhesion or Ab-mediated clustering. MAPKs were involved in ICAM-1-dependent expression of TNF-α in cerebral and dermal MVECs, and CXCL8, CCL3, CCL4, VCAM-1, and cyclooxygenase 2 (COX-2) in cerebral MVECs. Endothelial JNK and to a much lesser degree p38 were the principal MAPKs involved in facilitating diapedesis of CD4(+) lymphocytes across both types of MVECs, whereas ERK was additionally required for TEM across dermal MVECs. JNK activity was critical for ICAM-1-induced F-actin rearrangements. Furthermore, activation of endothelial ICAM-1/JNK led to phosphorylation of paxillin, its association with VE-cadherin, and internalization of the latter. Importantly ICAM-1-induced phosphorylation of paxillin was required for lymphocyte TEM and converged functionally with VE-cadherin phosphorylation. Taken together we conclude that during lymphocyte TEM, ICAM-1 signaling diverges into pathways regulating lymphocyte diapedesis, and other pathways modulating gene expression thereby contributing to the long-term inflammatory response of the endothelium

Shear Wave Splitting Analysis to Estimate Fracture Orientation and Frequency Dependent Anisotropy

Shear wave splitting is a well-known method for indication of orientation, radius, and length of fractures in subsurface layers. In this paper, a three component near offset VSP data acquired from a fractured sandstone reservoir in southern part of Iran was used to analyse shear wave splitting and frequency-dependent anisotropy assessment. Polarization angle obtained by performing rotation on radial and transverse components of VSP data was used to determine the direction of polarization of fast shear wave which corresponds to direction of fractures. It was shown that correct implementation of shear wave splitting analysis can be used for determination of fracture direction. During frequency- dependent anisotropy analysis, it was found that the time delays in shear- waves decrease as the frequency increases. It was clearly demonstrated throughout this study that anisotropy may have an inverse relationship with frequency. The analysis presented in this paper complements the studied conducted by other researchers in this field of research

Identification of genes expressed by immune cells of the colon that are regulated by colorectal cancer-associated variants.

A locus on human chromosome 11q23 tagged by marker rs3802842 was associated with colorectal cancer (CRC) in a genome-wide association study; this finding has been replicated in case-control studies worldwide. In order to identify biologic factors at this locus that are related to the etiopathology of CRC, we used microarray-based target selection methods, coupled to next-generation sequencing, to study 103 kb at the 11q23 locus. We genotyped 369 putative variants from 1,030 patients with CRC (cases) and 1,061 individuals without CRC (controls) from the Ontario Familial Colorectal Cancer Registry. Two previously uncharacterized genes, COLCA1 and COLCA2, were found to be co-regulated genes that are transcribed from opposite strands. Expression levels of COLCA1 and COLCA2 transcripts correlate with rs3802842 genotypes. In colon tissues, COLCA1 co-localizes with crystalloid granules of eosinophils and granular organelles of mast cells, neutrophils, macrophages, dendritic cells and differentiated myeloid-derived cell lines. COLCA2 is present in the cytoplasm of normal epithelial, immune and other cell lineages, as well as tumor cells. Tissue microarray analysis demonstrates the association of rs3802842 with lymphocyte density in the lamina propria (p = 0.014) and levels of COLCA1 in the lamina propria (p = 0.00016) and COLCA2 (tumor cells, p = 0.0041 and lamina propria, p = 6 × 10(-5)). In conclusion, genetic, expression and immunohistochemical data implicate COLCA1 and COLCA2 in the pathogenesis of colon cancer. Histologic analyses indicate the involvement of immune pathways

The relationship between parent and child dysfunctional beliefs about sleep and child sleep

Cognitive theories emphasise the role of dysfunctional beliefs about sleep in the development and maintenance of sleep-related problems (SRPs). The present research examines how parents' dysfunctional beliefs about children's sleep and child dysfunctional beliefs about sleep are related to each other and to children's subjective and objective sleep. Participants were 45 children aged 11 -12 years and their parents. Self-report measures of dysfunctional beliefs about sleep and child sleep were completed by children, mothers and fathers. Objective measures of child sleep were taken using actigraphy. The results showed that child dysfunctional beliefs about sleep were correlated with father (r=.43, p<.05) and mother (r=.43, p<.05) reported child SRPs, and with Sleep Onset Latency (r=.34, p<.05). Maternal dysfunctional beliefs about child sleep were related to child SRPs as reported by mothers (r=.44, p<.05), and to child dysfunctional beliefs about sleep (r=.37, p<.05). Some initial evidence was found for a mediation pathway in which child dyfunctional beliefs mediate the relationship between parent dysfunctional beliefs and child sleep. The results support the cognitive model of SRPs and contribute to the literature by providing the first evidence of familial aggregation of dysfunctional beliefs about sleep

Total versus partial knee replacement in patients with medial compartment knee osteoarthritis : the TOPKAT RCT

Article history The research reported in this issue of the journal was funded by the HTA programme as project number 08/14/08. The contractual start date was in January 2010. The draft report began editorial review in February 2019 and was accepted for publication in October 2019. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Acknowledgements TOPKAT study group Chief investigator David Beard. Trial co-investigators Nigel Arden (Oxford), Helen Campbell (Oxford), Marion Campbell (Aberdeen), Andrew Carr (Oxford), Jonathan Cook (Aberdeen then Oxford), Helen Doll (Oxford), Ray Fitzpatrick (Oxford), David Murray (Oxford) and Andrew Price (Oxford). Trial management Mayret Castillo (until 2011), Cushla Cooper, Loretta Davies, Anne Duncan (until 2017), Gordon Fernie, Sophie Halpin (until 2015) and Alison McDonald. Trial administration Katie Chegwin, Jiyang Li (until 2018), Elena Rabaiotti (until 2013), Sandra Regan (until 2012) and Victoria Stalker (until 2014). Data management Diana Collins (until 2013), Janice Cruden, Akiko Greshon, Kay Holland and Beverley Smith (until 2017). Database/programming management Gladys McPherson. Trial statisticians Charles Boachie (until 2013), Jemma Hudson and Graeme MacLennan. Health economists Helen Campbell (until 2015), Francesco Fusco (until 2018), Seamus Kent and Jose Leal. We would also like to thank Hannah Wilson (DPhil student, University of Oxford) for her help with the update to the literature search. Research teams We are grateful to the participants and research teams at collaborating hospital sites: Aneurin Bevan University Health Board, Royal Gwent Hospital Ruth Jenkins, Mark Lewis [principal investigator (PI)] and Witek Mintowt-Czyz. Belfast Health and Social Care Trust, Musgrove Park Hospital, Belfast David Beverland (PI), Leeann Bryce, Julie Catney, Ian Dobie, Emer Doran and Seamus O’Brien. Chesterfield Royal Hospital NHS Foundation Trust Fazal Ali, Heather Cripps, Amanda Whileman, Phil Williams (PI) and Julie Toms. County Durham and Darlington NHS Foundation Trust Ellen Brown, Gillian Horner, Andrew Jennings (PI) and Glynis Rose. East Lancashire Hospitals NHS Trust, Royal Blackburn Hospital Frances Bamford, Wendy Goddard, Hans Marynissen (PI), Haleh Peel and Lyndsey Richards. Great Western Hospitals NHS Foundation Trust, Swindon Amanda Bell, Sunny Deo, Sarah Grayland, David Hollinghurst, Suzannah Pegler, Venkat Satish (PI) and Claire Woodruffe. Harrogate and District NHS Foundation Trust, Harrogate Nick London (PI), David Duffy, Caroline Bennett and James Featherstone. Hull and East Yorkshire Hospitals NHS Trust Joss Cook, Kim Dearnley, Nagarajan Muthukumar (PI), Laura Onuoha and Sarah Wilson. Maidstone and Tunbridge Wells NHS Trust, Medway Sandhu Banher, Eunice Emeakaroha, Jamie Horohan, Sunil Jain (PI) and Susan Thompson. Mid Yorkshire Hospitals NHS Trust Sarah Buckley, Aaron Ng (PI), Ajit Shetty and Karen Simeson. Milton Keynes University Hospital NHS Foundation Trust Julian Flynn, Meryl Newsom, Cheryl Padilla-Harris and Oliver Pearce (PI). NHS Grampian, Woodend Hospital, Aberdeen James Bidwell (PI), Alison Innes, Winifred Culley and Bill Ledingham and Janis Stephen. North Bristol NHS Trust Rachel Bray, Hywel Davies, Debbie Delgado, Jonathan Eldridge, Leigh Morrison, James Murray (PI), Andrew Porteous and James Robinson. North Cumbria University Hospitals NHS Trust, Carlisle Matt Dawson (PI), Raj Dharmarajan, David Elson, Will Hage, Nicci Kelsall and Mike Orr. North Tees and Hartlepool NHS Foundation Trust, Stockton-On-Tees Jackie Grosvenor, SS Maheswaran (PI), Claire McCue, Hemanth Venkatesh, Michelle Wild and Deborah Wilson. Oxford University Hospitals NHS Trust, Nuffield Orthopaedic Centre Chris Dodd, William Jackson (PI), Pam Lovegrove, David Murray, Jennifer Piper and Andrew Price. Royal United Hospitals Bath NHS Foundation Trust, Bath Neil Bradbury, Lucy Clark, Stefanie Duncan, Genevieve Simpson and Allister Trezies (PI). Sherwood Forest Hospitals NHS Foundation Trust, Kings Mill Hospital, Sutton in Ashfield Vikram Desai (PI), Cheryl Heeley, Kramer Guy and Rosalyn Jackson. South Devon Healthcare NHS Foundation Trust, Torbay Alan Hall, Gordon Higgins (PI), Michael Hockings, David Isaac and Pauline Mercer. Stockport NHS Foundation Trust, Stockport Lindsey Barber, Helen Cochrane, Janette Curtis, Julie Grindey, David Johnson (PI), and Phil Turner. The Hillingdon Hospitals NHS Trust David Houlihan-Burne (PI), Briony Hill, Ron Langstaff and Mariam Nasseri. The Ipswich Hospital NHS Trust, Ipswich Mark Bowditch, Chris Martin, Steven Pryke, Bally Purewal, Chris Servant (PI), Sheeba Suresh and Claire Tricker. University Hospitals of Leicester NHS Trust, Leicester Robert Ashford, Manjit Attwal, Jeanette Bunga, Urjit Chatterji, Susan Cockburn, Colin Esler (PI), Steven Godsiff, Tim Green, Christina Haines and Subash Tandon. University Hospitals of North Midlands NHS Trust, Stoke on Trent Racquel Carpio, Sarah Griffiths, Natalie Grocott and Ian dos Remedios (PI). University Hospital Southampton NHS Foundation Trust David Barrett, Phil Chapman-Sheath, Caroline Grabau, Jane Moghul, William Tice (PI) and Catherine Trevithick. United Lincolnshire Hospitals NHS Trust, Boston Rajiv Deshmukh, Mandy Howes, Kimberley Netherton, Dipak Raj (PI) and Nikki Travis. United Lincolnshire Hospitals NHS Trust, Lincoln Mohammad Maqsood, Rebecca Norton, Farzana Rashid, Alison Raynor, Mark Rowsell and Karen Warner. We would like to thank the external members of the TSC and DMC for their advice and support for the project. Trial Steering Committee Donna Dodwell as our patient representative, Simon Donell (chairperson) (University of East Anglia), Shawn Tavares (Royal Berkshire Hospital) and Jonathan Waite (South Warwickshire NHS Foundation Trust). Data Monitoring Committee Karen Barker (Oxford University Hospitals NHS Foundation Trust), Gordon Murray (chairperson) (University of Edinburgh) and Hamish Simpson (University of Edinburgh). Independent review and interpretation of results Professor David Torgerson (University of York). Professor Chris Maher (University of Sydney). Mr Peter Brownson (The Royal Liverpool and Broadgreen University Hospitals NHS Trust). Professor Simon Donell (University of East Anglia, Norwich). Mr Mark Mullins (Abertawe Bro Morgannwg University Health Board). Professor Jane Blazeby (Bristol University).Peer reviewedPublisher PD