Transition Metal-Substituted Krebs-Type Polyoxometalate-Doped PEDOT Films.

The transition metal-substituted Krebs-type polyoxometalates (POMs) [Sb2W20M2O70(H2O)6]n-, M = Fe(III), Co(II), or Cu(II), were surface immobilized within the conducting polymer 3,4-ethylenedioxythiophene (PEDOT) on glassy carbon electrode surfaces. The immobilized films of different thicknesses were characterized by electrochemical and surface-based techniques. The inherent redox activity for the Krebs-type POMs, [Sb2W20M2O70(H2O)6]n-, M = Fe(III), Co(II), or Cu(II), that were observed in the solution phase were maintained in the polymeric PEDOT matrix. The resulting films were found to be extremely stable toward redox switching between the various POM-based redox states. The films exhibited pH-dependent redox activity and thin layer behavior up to 100 mV s-1. The films were found to be highly conductive through the employment of electrochemical impedance spectroscopy. Surface characterization of the films was carried out by X-ray photoelectron spectroscopy, atomic force microscopy, and scanning electron microscopy graph.

Neurogenic hypertension and elevated vertebrobasilar arterial resistance: is there a causative link?

There is evidence of sympathetic overdrive in a significant proportion of patients with essential hypertension and an animal model of the condition, the spontaneously hypertensive rat (SHR). The reasons for this remain elusive. However, there is also evidence of narrowing of the arteries supplying the brainstem in the SHR and hypertensive humans. In this review, we discuss the possible role of brainstem hypoperfusion in driving increased sympathetic activity and hypertension.

A pilot study: are dental hygienists in Texas ready for the elderly population explosion?

PURPOSE: At the beginning of the 20th century, people 65 and older comprised 4.1% of the population. By the year 2030, it is estimated that people 65 and older, the 'Baby Boomer' generation, will comprise more than 20% of the population. This will have a profound effect on the practice of dentistry and on society as a whole. The purpose of this study was to determine whether dental hygienists in Texas felt prepared and willing to treat the elderly in alternative practice settings such as nursing homes. METHODS: After institutional review board approval, a questionnaire was mailed to 500 hygienists. A 5% systematic sample of dental hygiene graduates was taken from four dental hygiene schools in Texas, United States of America (USA). Of these, 175 were returned for a 35% response rate. Questions asked were degree held, how prepared the participants felt to treat the special needs of the elderly, if participants were willing to work in alternative practice settings such as a nursing home and if they felt additional education was needed. Frequency distributions, correlations and chi square were used to analyse the data. RESULTS: Results revealed 86.5% of the respondents felt prepared to somewhat prepared to treat the special needs of the elderly based on education; equally, 86.5% felt more education was needed to better prepare them to treat the elderly. Over half of the respondents would not be willing to work in alternative practice settings such as nursing homes. CONCLUSION: The average respondents do not feel fully prepared to treat the elderly with special needs, and they think more education is needed to better prepare them to treat this important target population.

Mechanisms of Atomization from Rotary Dental Instruments and Its Mitigation.

Since the onset of coronavirus disease 2019, the potential risk of dental procedural generated spray emissions (including aerosols and splatters), for severe acute respiratory syndrome coronavirus 2 transmission, has challenged care providers and policy makers alike. New studies have described the production and dissemination of sprays during simulated dental procedures, but findings lack generalizability beyond their measurements setting. This study aims to describe the fundamental mechanisms associated with spray production from rotary dental instrumentation with particular focus on what are currently considered high-risk components-namely, the production of small droplets that may remain suspended in the room environment for extended periods and the dispersal of high-velocity droplets resulting in formites at distant surfaces. Procedural sprays were parametrically studied with variables including rotation speed, burr-to-tooth contact, and coolant premisting modified and visualized using high-speed imaging and broadband or monochromatic laser light-sheet illumination. Droplet velocities were estimated and probability density maps for all laser illuminated sprays generated. The impact of varying the coolant parameters on heating during instrumentation was considered. Complex structured sprays were produced by water-cooled rotary instruments, which, in the worst case of an air turbine, included droplet projection speeds in excess of 12 m/s and the formation of millions of small droplets that may remain suspended. Elimination of premisting (mixing of coolant water and air prior to burr contact) resulted in a significant reduction in small droplets, but radial atomization may still occur and is modified by burr-to-tooth contact. Spatial probability distribution mapping identified a threshold for rotation speeds for radial atomization between 80,000 and 100,000 rpm. In this operatory mode, cutting efficiency is reduced but sufficient coolant effectiveness appears to be maintained. Multiple mechanisms for atomization of fluids from rotatory instrumentation exist, but parameters can be controlled to modify key spray characteristics during the current crisis.

Hemispherical differences in the shape and topography of asteroid (101955) Bennu.

We investigate the shape of near-Earth asteroid (101955) Bennu by constructing a high-resolution (20 cm) global digital terrain model from laser altimeter data. By modeling the northern and southern hemispheres separately, we find that longitudinal ridges previously identified in the north extend into the south but are obscured there by surface material. In the south, more numerous large boulders effectively retain surface materials and imply a higher average strength at depth to support them. The north has fewer large boulders and more evidence of boulder dynamics (toppling and downslope movement) and surface flow. These factors result in Bennu's southern hemisphere being rounder and smoother, whereas its northern hemisphere has higher slopes and a less regular shape. We infer an originally asymmetric distribution of large boulders followed by a partial disruption, leading to wedge formation in Bennu's history.

Harvey Cushing and the regulation of blood pressure in giraffe, rat and man: introducing 'Cushing's mechanism'.

The fundamental mechanism that underlies essential hypertension is a high total peripheral resistance. We review here possible origins of high total peripheral resistance in physiologically hypertensive giraffes, spontaneously hypertensive rats and humans with essential hypertension. We propose that a common link could be reduced brainstem perfusion, as first suggested by Cushing in 1901. Any tendency towards reduction of cerebral blood flow to the cardiovascular control centres in rest and sleep will be prevented by activation of a response arising in the brainstem. The response will proportionately increase systemic blood pressure and return cerebral blood flow to a new homeostatic level. New evidence we review here supports this idea and leads us to suggest that central regulation of blood pressure has two components: the classic Cushing's response, which is a terminal event, and a Cushing's mechanism, which is a physiological mechanism for long-term control of mean arterial pressure. In giraffes, Cushing's mechanism is activated by increasing neck length during growth and subsequent gravitational hypotension that stimulates a rise in basal arterial blood pressure. In man and rats, the mechanism is activated by narrowing of the arteries supplying the brainstem. If we are correct, future successful treatment of essential hypertension in man will include methods of reducing cerebral arterial resistance.

Growth-promoting effects of glycine-extended progastrin.

Peptide alpha amidation is required to produce some hormones, such as gastrin, from their glycine-extended precursors. This terminal posttranslational processing reaction is thought to be essential for the biological activation of many peptide hormones; only amidated gastrin exerts a physiological effect that results in gastric acid secretion. However, both amidated gastrin and glycine-extended gastrin stimulate proliferation of exocrine pancreatic cell line AR4-2J through selective receptors for the substrate and the product, respectively, of peptide alpha amidation. Thus, the amidation reaction may function as a determinant of the specific biological actions of products derived from prohormones.

The C-Band All-Sky Survey (C-BASS): Simulated parametric fitting in single pixels in total intensity and polarization.

The cosmic microwave background (CMB) B-mode signal is potentially weaker than the diffuse Galactic foregrounds over most of the sky at any frequency. A common method of separating the CMB from these foregrounds is via pixel-based parametric-model fitting. There are not currently enough all-sky maps to fit anything more than the most simple models of the sky. By simulating the emission in seven representative pixels, we demonstrate that the inclusion of a 5 GHz data point allows for more complex models of low-frequency foregrounds to be fitted than at present. It is shown that the inclusion of the C-BASS data will significantly reduce the uncertainties in a number of key parameters in the modelling of both the galactic foregrounds and the CMB. The extra data allow estimates of the synchrotron spectral index to be constrained much more strongly than is presently possible, with corresponding improvements in the accuracy of the recovery of the CMB amplitude. However, we show that to place good limits on models of the synchrotron spectral curvature will require additional low-frequency data.

Wheelchair users: a guide for the GDP.

The number of wheelchair users in the UK is increasing, and it may be more convenient and appropriate for many of these individuals to receive their dental care in a general dental practice rather than in a community or tertiary facility. This article is intended to provide the average general dental practitioner (GDP) with the basic tools and increased confidence to effectively triage this cohort of the population, and accept them for treatment or refer appropriately.

Specificity of prohormone convertase endoproteolysis of progastrin in AtT-20 cells.

Biologically active peptide hormones are synthesized from larger precursor proteins by a variety of posttranslational processing reactions. Endoproteolytic cleavage at the Lys74-Lys75 dibasic processing site of progastrin is the major determinant for the relative distribution of gastrin heptadecapeptide and tetratriacontapeptide in tissues. Thus, we explored the ability of two prohormone convertases, PC1/PC3 and PC2, to cleave this important site within progastrin. We expressed wild-type human gastrin cDNA and mutant cDNAs in which the Lys74Lys75 site was changed to Lys74Arg75, Arg74Arg75, and Arg74Lys75 residues in AtT-20 cells. Because AtT-20 cells express Pc1/PC3 but not PC2, we also coexpressed a cDNA encoding PC2 in both wild-type and mutant gastrin-producing AtT-20 cells. Wild-type Lys74Lys75 and mutant Arg74Arg75 progastrin processing sites were efficiently cleaved in AtT-20 cells only after coexpression of PC2. Mutant Lys74Arg75 progastrin was readily processed in cells in the presence or absence of PC2 coexpression, but, in contrast, mutant Arg74Lys75 progastrin was inefficiently cleaved regardless of PC2 coexpression. Northern analysis revealed the presence of PC2 but not PC1/ PC3 in canine antral gastrin-producing G cells. These data suggest that PC2 but not PC1/PC3 is responsible for the cleavage of the Lys74Lys75 site in wild-type progastrin.

Intracerebral haemorrhage revisited.

Much evidence suggests that acute intracerebral haemorrhage usually starts to appear an hour or two after a thromboembolic brain infarct. Intravenous thrombolytic treatment is accepted treatment for acute ischaemic stroke; but all neurologists concur that brain imaging should be performed first, so that thrombolysis can be avoided if bleeding has already started. This article calls into question the current guidelines for the use of thrombolytic treatment in acute stroke. Are they too restrictive?

Compliance with occupational exposure risk management procedures in a dental school setting.

Background The Dental Institute at King's College London has recently implemented changes focusing on infection control, including safety needle provision, personal protective equipment campaigns, mandatory lectures and formal assessment for students. We explored the effect of these changes over a five-year period.Methods We observed 49 clinical consultations in 2010 and 50 in 2014, examining clinician attire, personal protective equipment, dental operatory management, sharps hazards and aseptic technique.Results One hundred percent of operators wore gloves, apron and masks, 94% wore eye protection, 98% had uncovered wrists and 88% had tidy hair. Ninety-four percent wore safe shoes, 86% were of appropriate material, and 70-82% demonstrated correct zoning technique. Safe sharps bin placement improved from 78% to 100%, 92% were not overfilled, and 96% were free from protruding items. Sixty-eight percent of bays were appropriately barrier wrapped, 78-88% were kept tidy and 96% were free of items that could have been disposed of immediately following use. Ninety to ninety-eight percent of ultrasonic tips and 64% of burs were removed from handpieces when not in use.Conclusion Dental healthcare workers are at risk of significant occupational exposures, which can be minimised by technological advances, implementation of best practice guidelines, optimisation of the clinical working environment and reinforcement of infection control policy.

A review of gagging problems in dentistry: aetiology and classification.

Some people have a pronounced gag reflex that can be a severe limitation to their ability to accept dental care and the clinician's ability to provide it. It can compromise all aspects of dentistry, from diagnostic procedures to active treatment and can be distressing for all concerned. Many techniques have been described that attempt to overcome the problem. Dentists will undoubtedly see patients with gagging problems and knowledge of a variety of management strategies is necessary to aid the delivery of dental care. This first paper looks at the background to gagging problems and their classification and categorization prior to clinical treatment. The second article will look at the clinical assessment of the patient presenting for dental treatment with a history of gagging problems. It will also review methods used to manage patients with gagging reflexes during dental treatment.

A review of gagging problems in dentistry: 2. Clinical assessment and management.

A pronounced gag reflex can be a severe limitation to a patient's ability to accept dental care and for a clinician's ability to provide it. It can compromise all aspects of dentistry from diagnostic procedures to active treatment and can be distressing for all concerned. Many 'management' techniques have been described. This paper describes the different categories of treatment used to manage people with pronounced gag reflexes.

Discrimination between constitutive secretion and basal secretion from the regulated secretory pathway in GH3 cells.

The present experiments were undertaken to characterize basal release from vesicles of the regulated secretory pathway. In transfected GH3 cells, progastrin was released by the constitutive route, and mature, bioactive, amidated gastrin by the regulated secretory pathway. Studies using brefeldin A and bafilomycin A1 which inhibit progression through the Golgi complex suggested that both basal and stimulated release of amidated gastrin originated from mature secretory granules. Basal, but not stimulated, secretion of amidated gastrin was strongly inhibited at 22 degrees C. Mature secretory vesicles therefore support both basal and evoked secretion although the mechanisms underlying the two processes differ in their temperature sensitivity.

Influence of cofactor binding and active site occupancy on the conformation of the macromolecular substrate exosite of factor VIIa.

The catalytic activity of the trypsin-like serine protease coagulation factor VIIa is allosterically regulated. In this work, we employed monoclonal antibodies as probes to analyze conformational changes in the VII protease domain that are induced by zymogen activation, cofactor tissue factor (TF) binding, and active site occupancy. The epitopes of three monoclonal antibodies were mapped using a panel of 57 individual alanine replacement mutants in the protease domain. Two of the antibodies had typical "hot spot" epitopes in a basic cluster above the active site cleft and antibody binding to these epitopes was not affected by zymogen activation, TF binding, or active site occupancy. In contrast, the binding kinetics of VII/VIIa to a monoclonal antibody that mapped to an extended epitope overlapping with the macromolecular substrate exosite was affected by each of the conformational transitions of the VIIa protease domain. The changes in antibody affinity are consistent with a transition from zymogen VII to the TF.VIIa complex, with free enzyme VIIa as an intermediate that retains some zymogen-like features responsible for its low catalytic activity. In contrast, active site occupancy resulted in effects that were qualitatively different from the effects of zymogen activation on the antibody epitope. This provides novel insight into the conformational interdependence between the active site, the region for macromolecular substrate recognition, and the cofactor binding exosite of this allosterically regulated serine protease.

Crystals of the cell-binding module of fibronectin obtained from a series of recombinant fragments differing in length.

A recombinant fragment corresponding to the cell adhesion module (FNIII10) of human fibronectin has been crystallized at pH 8.6 from solutions containing polyethylene glycol as precipitant. The crystals formed in the space group P2(1) with a = 30.76 A, b = 35.07 A, c = 37.66 A, beta = 106.9 degrees. There is one molecule per asymmetric unit and the crystals diffract beyond 1.75 A resolution. To improve the prospects for successful crystallization of the FNIII10 module, a series of recombinant fragments was produced with minor differences in the length of N or C-terminal segments. Only one of these variants crystallized. Interestingly, the C-terminal residue of this variant formed stable intermolecular contacts with a symmetry-related molecule in the crystal lattice.

Crystal structure of the tenth type III cell adhesion module of human fibronectin.

The crystal structure of the cell adhesion module of fibronectin (FNIII10) has been determined at 1.8 A resolution. A recombinant fragment corresponding to the tenth type III module of human fibronectin was crystallized in space group P2(1) with a = 30.7, b = 35.1 and c = 37.7 A and beta = 107 degrees. The structure was determined by molecular replacement and refined by least squares methods. The crystallographic R-factor for the final model of the 91 amino acid module plus 56 solvent atoms is 0.18 for 10 to 1.8 A data. The module consists of two layers of beta-sheet, one with three antiparallel strands and the other with four antiparallel strands. The beta-sheets enclose a hydrophobic core of 24 amino acid side-chains. The module contains the RGD cell recognition sequence in a flexible loop connecting two beta-strands. The tertiary structure of the FNIII10 module has been used to develop a structure-based sequence alignment of 17 type III modules in fibronectin based on the striking conservation of homologous hydrophobic residues. A similar pattern of homologous alternating hydrophobic residues is also evident in a comparison of type III modules in proteins unrelated to fibronectin such as cytokine receptors and muscle proteins.

Characterization of Agouti-related protein binding to melanocortin receptors.

Agouti-related protein (AGRP) is a naturally occurring antagonist of melanocortin action that is thought to play an important role in the hypothalamic control of feeding behavior. The exact mechanism of AGRP and Agouti protein action has been difficult to examine, in part because of difficulties in producing homogeneous forms of these molecules that can be used for direct binding assays. In this report we describe the application of chemical protein synthesis to the construction of two novel AGRP variants. Examination of the biological activity of the AGRP variants demonstrates that a truncated variant, human AGRP(87-132), a 46-amino acid variant based on the carboxyl-terminal cysteine-rich domain of AGRP, is equipotent to an 111-amino acid variant, mouse [Leu127Pro]AGRP (mature AGRP minus its signal sequence), in its ability to dose dependently inhibit alpha-MSH-generated cAMP generation at the cloned melanocortin receptors. Furthermore, deletion of the amino-terminal portion of the full-length variant did not alter the MCR subtype specificity of AGRP(87-132). Finally, iodination of human AGRP(87-132) provided a useful reagent with which the binding properties of AGRP could be analyzed. In both conventional and photoemulsion binding studies [125I]AGRP(87-132) was observed only to bind to cells expressing melanocortin receptors MC3R, MC4R, and MC5R. These results demonstrate that the residues critical for receptor binding, alpha-MSH inhibition, and melanocortin receptor subtype specificity are all located in the carboxyl terminus of the molecule. Because [Nle4, D-Phe7] (NDP)-MSH displaces the binding of [125I]AGRP(87-132) to MCRs and AGRP(87-132) displaces the binding of [125I]NDP-MSH, we conclude that these molecules bind in a competitive fashion to melanocortin receptors.