Identification of salivary mucin MUC7 binding proteins from Streptococcus gordonii

<p>Abstract</p> <p>Background</p> <p>The salivary mucin MUC7 (previously known as MG2) can adhere to various strains of streptococci that are primary colonizers and predominant microorganisms of the oral cavity. Although there is a growing interest in interaction between oral pathogens and salivary mucins, studies reporting the specific binding sites on the bacteria are rather limited. Identification and characterization of the specific interacting proteins on the bacterial cell surface, termed adhesins, are crucial to further understand host-pathogen interactions.</p> <p>Results</p> <p>We demonstrate here, using purified MUC7 to overlay blots of SDS-extracts of <it>Streptococcus gordonii </it>cell surface proteins, 4 MUC7-binding bands, with apparent molecular masses of 62, 78, 84 and 133 kDa from the <it>Streptococcus gordonii </it>strain, PK488. Putative adhesins were identified by in-gel digestion and subsequent nanoLC-tandem mass spectrometry analysis of resultant peptides. The 62 kDa and 84 kDa bands were identified as elongation factor (EF) Tu and EF-G respectively. The 78 kDa band was a <it>hppA </it>gene product; the 74 kDa oligopeptide-binding lipoprotein. The 133 kDa band contained two proteins; alpha enolase and DNA-directed RNA polymerase, beta' subunit. Some of these proteins, for example alpha enolase are expected to be intracellular, however, flow cytometric analysis confirmed its location on the bacterial surface.</p> <p>Conclusion</p> <p>Our data demonstrated that <it>S. gordonii </it>expressed a number of putative MUC7 recognizing proteins and these contribute to MUC7 mucin binding of this streptococcal strain.</p

Altered hippocampal function in major depression despite intact structure and resting perfusion

Background: Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation. Method: A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed. Results: The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow. Conclusions: Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression

Authority and the Future of Consent in Population-Level Biomedical Research

Population-level biomedical research has become crucial to the health system’s ability to improve the health ofthe population. This form of research raises a number of well-documented ethical concerns, perhaps the mostsignificant of which is the inability of the researcher to obtain fully informed specific consent from participants.Two proposed technical solutions to this problem of consent in large-scale biomedical research that havebecome increasingly popular are meta-consent and dynamic consent. We critically examine the ethical andpractical credentials of these proposals and find them lacking. We suggest that the consent problem is notsolved by adopting a technology driven approach grounded in a notion of ‘specific’ consent but by takingseriously the role of research governance in combination with broader conceptions of consent. In our view, theseapproaches misconstrue the rightful location of authority in the way in which population-level biomedicalresearch activities are structured and organized. We conclude by showing how and why the authority fordetermining the nature and shape of choice making about participation ought not to lie with individual participants, but rather with the researchers and the research governance process, and that this necessarily leads tothe endorsement of a fully articulated broad consent approach

Dune formation on the present Mars

We apply a model for sand dunes to calculate formation of dunes on Mars under the present Martian atmospheric conditions. We find that different dune shapes as those imaged by Mars Global Surveyor could have been formed by the action of sand-moving winds occuring on today's Mars. Our calculations show, however, that Martian dunes could be only formed due to the higher efficiency of Martian winds in carrying grains into saltation. The model equations are solved to study saltation transport under different atmospheric conditions valid for Mars. We obtain an estimate for the wind speed and migration velocity of barchan dunes at different places on Mars. From comparison with the shape of bimodal sand dunes, we find an estimate for the timescale of the changes in Martian wind regimes.Comment: 16 pages, 12 figure

An occupational therapy intervention for residents with stroke related disabilities in UK care homes (OTCH): cluster randomised controlled trial

Objective To evaluate the clinical efficacy of an established programme of occupational therapy in maintaining functional activity and reducing further health risks from inactivity in care home residents living with stroke sequelae. Design Pragmatic, parallel group, cluster randomised controlled trial. Setting 228 care homes (>10 beds each), both with and without the provision of nursing care, local to 11 trial administrative centres across the United Kingdom. Participants 1042 care home residents with a history of stroke or transient ischaemic attack, including those with language and cognitive impairments, not receiving end of life care. 114 homes (n=568 residents, 64% from homes providing nursing care) were allocated to the intervention arm and 114 homes (n=474 residents, 65% from homes providing nursing care) to standard care (control arm). Participating care homes were randomised between May 2010 and March 2012. Intervention Targeted three month programme of occupational therapy, delivered by qualified occupational therapists and assistants, involving patient centred goal setting, education of care home staff, and adaptations to the environment. Main outcome measures Primary outcome at the participant level: scores on the Barthel index of activities of daily living at three months post-randomisation. Secondary outcome measures at the participant level: Barthel index scores at six and 12 months post-randomisation, and scores on the Rivermead mobility index, geriatric depression scale-15, and EuroQol EQ-5D-3L questionnaire, at all time points. Results 64% of the participants were women and 93% were white, with a mean age of 82.9 years. Baseline characteristics were similar between groups for all measures, personal characteristics, and diagnostic tests. Overall, 2538 occupational therapy visits were made to 498 participants in the intervention arm (mean 5.1 visits per participant). No adverse events attributable to the intervention were recorded. 162 (11%) died before the primary outcome time point, and 313 (30%) died over the 12 months of the trial. The primary outcome measure did not differ significantly between the treatment arms. The adjusted mean difference in Barthel index score at three months was 0.19 points higher in the intervention arm (95% confidence interval −0.33 to 0.70, P=0.48). Secondary outcome measures also showed no significant differences at all time points. Conclusions This large phase III study provided no evidence of benefit for the provision of a routine occupational therapy service, including staff training, for care home residents living with stroke related disabilities. The established three month individualised course of occupational therapy targeting stroke related disabilities did not have an impact on measures of functional activity, mobility, mood, or health related quality of life, at all observational time points. Providing and targeting ameliorative care in this clinically complex population requires alternative strategies

Millimetre observations of Pleiades stars: a lack of solar-analogue planetesimal discs at 100 Myr?

Solar analogues approximately 100 Myr old may have dusty debris from collisions within evolving cometary belts, and such remnant discs might also be associated with earlier stellar-spin braking. We observed at 1.2 mm wavelength a sample of 17 fast and slow rotators, mostly single K dwarfs, in the 100 Myr Pleiades cluster. No dust was detected for individual stars or the ensemble, so there are no cold massive debris discs nor any discernible relation of such distant material to stellar spin. The net limits from these data and our earlier far-infrared results imply that the typical Pleiades G/K dwarf has a relative disc-to-star luminosity ≲ 2 × 10^(−4). Collisional evolution models have predicted greater luminosities at the 10^8 yr epoch, for debris discs evolving out of a proto-solar nebula. This suggests that substantial primordial discs such as that of the Sun are not the norm amongst young solar analogues, or that dynamical interactions with giant planets can remove much of the comet belt by as early as 100 Myr

Service user, carer and provider perspectives on integrated care for older people with frailty, and factors perceived to facilitate and hinder implementation: A systematic review and narrative synthesis

© 2019 Sadler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction Older people with frailty (OPF) can experience reduced quality of care and adverse outcomes due to poorly coordinated and fragmented care, making this patient population a key target group for integrated care. This systematic review explores service user, carer and provider perspectives on integrated care for OPF, and factors perceived to facilitate and hinder implementation, to draw out implications for policy, practice and research. Methods Systematic review and narrative synthesis of qualitative studies identified from MEDLINE, CINAHL, PsycINFO and Social Sciences Citation Index, hand-searching of reference lists and citation tracking of included studies, and review of experts’ online profiles. Quality of included studies was appraised with The Critical Appraisal Skills Programme tool for qualitative research. Results Eighteen studies were included in the synthesis. We identified four themes related to stakeholder perspectives on integrated care for OPF: different preferences for integrated care among service users, system and service organisation components, relational aspects of care and support, and stakeholder perceptions of outcomes. Service users and carers highlighted continuity of care with a professional they could trust, whereas providers emphasised improved coordination of care between providers in different care sectors as key strategies for integrated care. We identified three themes related to factors facilitating and hindering implementation: perceptions of the integrated care intervention and target population, service organisational factors and system level factors influencing implementation. Different stakeholder groups perceived the complexity of care needs of this patient population, difficulties with system navigation and access, and limited service user and carer involvement in care decisions as key factors hindering implementation. Providers mainly also highlighted other organisational and system factors perceived to facilitate and hinder implementation of integrated care for OPF

Constraining the Chemical Signatures and the Outburst Mechanism of the Class 0 Protostar HOPS 383

We present observations toward HOPS 383, the first known outbursting Class 0 protostar located within the Orion molecular cloud using ALMA, VLA, and SMA. The SMA observations reveal envelope scale continuum and molecular line emission surrounding HOPS 383 at 0.85 mm, 1.1 mm, and 1.3 mm. The images show that HCO$^+$ and H$^{13}$CO$^+$ peaks on or near the continuum, while N$_2$H$^+$ is reduced at the same position. This reflects the underlying chemistry where CO evaporating close to the protostar destroys N$_2$H$^+$ while forming HCO$^+$. We also observe the molecular outflow traced by $^{12}$CO ($J = 2 \rightarrow 1$) and ($J = 3 \rightarrow 2$). A disk is resolved in the ALMA 0.87 mm dust continuum, orthogonal to the outflow direction, with an apparent radius of $\sim$62 AU. Radiative transfer modeling of the continuum gives disk masses of 0.02 M$_{\odot}$ when fit to the ALMA visibilities. The models including VLA 8 mm data indicate that the disk mass could be up to a factor of 10 larger due to lower dust opacity at longer wavelengths. The disk temperature and surface density profiles from the modeling, and an assumed protostar mass of 0.5 M$_{\odot}$ suggest that the Toomre $Q$ parameter $< 1$ before the outburst, making gravitational instability a viable mechanism to explain outbursts at an early age if the disk is sufficiently massive.Comment: Accepted by Ap