Remineralising effects of fluoride varnishes containing calcium phosphate on artificial root caries lesions with adjunctive application of proanthocyanidin

Objectives: To evaluate the remineralising effects of fluoride (F) varnishes containing bioavailable calcium-phosphate compound (Ca-P) based remineralisation systems and 5000 ppm F toothpaste (FTP) on root caries lesions (RCLs) and the potential effects of proanthocyanidin (PA) for the treatments of RCLs when used as an adjunct to F regimens. Methods: Demineralised root dentine and a pH-cycling model were used to mimic RCLs and the oral environment. Remineralising effects of MI VarnishTM (MIV) containing casein phosphopeptide–amorphous calcium phosphate (CPP-ACP) and Clinpro™ White Varnish (CPWV) containing tri-calcium phosphate (TCP) along with FTP and PA were evaluated regarding the birefringence, elemental composition, mechanical properties and mineral density of remineralised dentine with DuraphatTM as a comparison. Results: MIV, CPWV and DuraphatTM promoted the incorporation of F into RCLs and increased mineral density but did not change microhardness of root dentine significantly. Surface microhardness increased significantly when MIV or CPWV was used with 5000 ppm FTP. Application of PA with F regimens significantly increased subsurface mineral density. When PA was applied with MIV or CPWV along with FTP, the highest ion uptake and relative mineral gain (%ΔZ) was achieved, and significant increase of microhardness was up to 30 μm depth. Generally, MIV was associated with a higher mineral content gain than CPWV. Significance: Treatment of carious root surfaces remains challenging due to the complex pathological processes and difficulty in restoring the highly organised structure of root dentine. Treatment strategies targeting both remineralisation and preservation of the dentinal organic matrix have the potential to improve the fluoride-mediated remineralisation approaches

Molecular analysis of endocrine disruption in hornyhead turbot at wastewater outfalls in southern california using a second generation multi-species microarray.

Sentinel fish hornyhead turbot (Pleuronichthysverticalis) captured near wastewater outfalls are used for monitoring exposure to industrial and agricultural chemicals of ~ 20 million people living in coastal Southern California. Although analyses of hormones in blood and organ morphology and histology are useful for assessing contaminant exposure, there is a need for quantitative and sensitive molecular measurements, since contaminants of emerging concern are known to produce subtle effects. We developed a second generation multi-species microarray with expanded content and sensitivity to investigate endocrine disruption in turbot captured near wastewater outfalls in San Diego, Orange County and Los Angeles California. Analysis of expression of genes involved in hormone [e.g., estrogen, androgen, thyroid] responses and xenobiotic metabolism in turbot livers was correlated with a series of phenotypic end points. Molecular analyses of turbot livers uncovered altered expression of vitellogenin and zona pellucida protein, indicating exposure to one or more estrogenic chemicals, as well as, alterations in cytochrome P450 (CYP) 1A, CYP3A and glutathione S-transferase-α indicating induction of the detoxification response. Molecular responses indicative of exposure to endocrine disruptors were observed in field-caught hornyhead turbot captured in Southern California demonstrating the utility of molecular methods for monitoring environmental chemicals in wastewater outfalls. Moreover, this approach can be adapted to monitor other sites for contaminants of emerging concern in other fish species for which there are few available gene sequences

Improved age estimates for key Late Quaternary European tephra horizons in the RESET lattice

The research project 'Response of Humans to Abrupt Environmental Transitions' (RESET) used tephra layers to tie together and synchronise the chronologies of stratigraphic records at archaeological and environmental sites. With the increasing importance of tephra as chronological markers in sedimentary sequences, both in this project and more generally, comes a requirement to have good estimates for the absolute age of these volcanic horizons. This paper summarises the chronology of the key tephra in the RESET tephra lattice in the time range 10-60 ka BP, from the existing literature, from papers produced as part of the RESET project, and reanalysis conducted for this paper. The paper outlines the chronological ap- proach taken to the dating of tephra within the RESET project, and the basis for further work, as part of the INTIMATE (INTegrating Ice core MArine and TEr- restrial records) initiative. For each of the tephra layers in the lattice, the existing literature is discussed and, where relevant date estimates updated using the latest radiocarbon calibration curves (IntCal13 and Marine13) and methods. Maps show the approximate extent of tephra finds, giving a visual indication of the coverage of the lattice in different time-periods.</p

Analysis of Endocrine Disruption in Southern California Coastal Fish Using an Aquatic Multispecies Microarray

BackgroundEndocrine disruptors include plasticizers, pesticides, detergents, and pharmaceuticals. Turbot and other flatfish are used to characterize the presence of chemicals in the marine environment. Unfortunately, there are relatively few genes of turbot and other flatfish in GenBank, which limits the use of molecular tools such as microarrays and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to study disruption of endocrine responses in sentinel fish captured by regulatory agencies.ObjectivesWe fabricated a multigene cross-species microarray as a diagnostic tool to screen the effects of environmental chemicals in fish, for which there is minimal genomic information. The array included genes that are involved in the actions of adrenal and sex steroids, thyroid hormone, and xenobiotic responses. This microarray will provide a sensitive tool for screening for the presence of chemicals with adverse effects on endocrine responses in coastal fish species.MethodsWe used a custom multispecies microarray to study gene expression in wild hornyhead turbot (Pleuronichthys verticalis) collected from polluted and clean coastal waters and in laboratory male zebrafish (Danio rerio) after exposure to estradiol and 4-nonylphenol. We measured gene-specific expression in turbot liver by qRT-PCR and correlated it to microarray data.ResultsMicroarray and qRT-PCR analyses of livers from turbot collected from polluted areas revealed altered gene expression profiles compared with those from nonaffected areas.ConclusionsThe agreement between the array data and qRT-PCR analyses validates this multispecies microarray. The microarray measurement of gene expression in zebrafish, which are phylogenetically distant from turbot, indicates that this multispecies microarray will be useful for measuring endocrine responses in other fish

Age-related fertility decline: is there a role for elective ovarian tissue cryopreservation?

Age-related fertility decline (ARFD) is a prevalent concern amongst western cultures due to the increasing age of first-time motherhood. Elective oocyte and embryo cryopreservation remain the most established methods of fertility preservation, providing women the opportunity of reproductive autonomy to preserve their fertility and extend their childbearing years to prevent involuntary childlessness. Whilst ovarian cortex cryopreservation has been used to preserve reproductive potential in women for medical reasons, such as in pre- or peripubertal girls undergoing gonadotoxic chemotherapy, it has not yet been considered in the context of ARFD. As artificial reproductive technology (ART) and surgical methods of fertility preservation continue to evolve, it is a judicious time to review current evidence and consider alternative options for women wishing to delay their fertility. This article critically appraises elective oocyte cryopreservation as an option for women who use it to mitigate the risk of ARFD and introduces the prospect of elective ovarian cortex cryopreservation as an alternative

The marine isotope stage 1–5 cryptotephra record of Tenaghi Philippon, Greece:Towards a detailed tephrostratigraphic framework for the Eastern Mediterranean region

The iconic climate archive of Tenaghi Philippon (TP), NE Greece, allows the study of short-term palaeoclimatic and environmental change throughout the past 1.3 Ma. To provide high-quality age control for detailed palaeoclimate reconstructions based on the TP archive, (crypto)tephra studies of a peat core ‘TP-2005’ have been carried out for the 0–130 ka interval. The results show that the TP basin is ideally positioned to receive tephra fall from both the Italian and Aegean Arc volcanic provinces. Two visible tephra layers, the Santorini Cape Riva/Y-2 (c. 22 ka) and the Campanian Ignimbrite (CI)/Y-5 (c. 39.8 ka) tephras, and six primary cryptotephra layers, namely the early Holocene E1 tephra from the Aeolian Islands (c. 8.3 ka), the Campanian Y-3 (c. 29 ka) and X-6 tephras (c. 109.5 ka), as well as counterpart tephras TM-18-1d (c. 40.4 ka), TM-23-11 (c. 92.4 ka) and TM-33-1a (c. 116.7 ka) from the Lago Grande di Monticchio sequence (southern Italy), were identified along with repeatedly redeposited Y-2 and CI tephra material. Bayesian modelling of the ages of seven of the primary tephra layers, 60 radiocarbon measurements and 20 palynological control points have been applied to markedly improve the chronology of the TP archive. This revised chronology constrains the age of tephra TM-18-1d to 40.90–41.66 cal ka BP (95.4% range). Several tephra layers identified in the TP record form important isochrons for correlating this archive with other terrestrial (e.g., Lago Grande di Monticchio, Sulmona Basin and Lake Ohrid) and marine (e.g., Adriatic Sea core PRAD 1-2 and Aegean Sea core LC21) palaeoclimate records in the Mediterranean region

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Measuring the Intrapersonal Component of Psychological Empowerment: Confirmatory Factor Analysis of the Sociopolitical Control Scale

The Sociopolitical Control Scale (SPCS) is a widely used measure of the intrapersonal component of psychological empowerment. Confirmatory factor analyses (CFA) were conducted with data from two samples to test the hypothesized structure of the SPCS, the potential effects of method bias on the measure's psychometric properties, and whether a revised version of the scale (SPCS‐R) yielded improved model fit. Sample 1 included 316 randomly selected community residents of the Midwestern United States. Sample 2 included 750 community residents of the Northeastern U.S. Results indicated that method bias from the use of negatively worded items had a significant effect on the factor structure of the SPCS. CFA of the SPCS‐R, in which negatively worded items were rephrased so that all statements were positively worded, supported the measure's hypothesized two‐factor structure (i.e., leadership competence and policy control). Subscales of the SPCS‐R were found reliable and related in expected ways with measures of community involvement. Implications of the study for empowerment‐based research and practice are described, and strategies to further develop the SPCS are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/117223/1/ajcp9070.pd

Mammalian and Invertebrate Models as Complementary Tools for Gaining Mechanistic Insight on Muscle Responses to Spaceflight

Bioinformatics approaches have proven useful in understanding biological responses to spaceflight. Spaceflight experiments remain resource intensive and rare. One outstanding issue is how to maximize scientific output from a limited number of omics datasets from traditional animal models including nematodes, fruitfly, and rodents. The utility of omics data from invertebrate models in anticipating mammalian responses to spaceflight has not been fully explored. Hence, we performed comparative analyses of transcriptomes of soleus and extensor digitorum longus (EDL) in mice that underwent 37 days of spaceflight. Results indicate shared stress responses and altered circadian rhythm. EDL showed more robust growth signals and Pde2a downregulation, possibly underlying its resistance to atrophy versus soleus. Spaceflight and hindlimb unloading mice shared differential regulation of proliferation, circadian, and neuronal signaling. Shared gene regulation in muscles of humans on bedrest and space flown rodents suggest targets for mitigating muscle atrophy in space and on Earth. Spaceflight responses of C. elegans were more similar to EDL. Discrete life stages of D. melanogaster have distinct utility in anticipating EDL and soleus responses. In summary, spaceflight leads to shared and discrete molecular responses between muscle types and invertebrate models may augment mechanistic knowledge gained from rodent spaceflight and ground-based studies