An immunohistochemical study of the localization and developmental expression of ghrelin and its functional receptor in the ovine placenta

<p>Abstract</p> <p>Background</p> <p>Ghrelin is an orexigenic hormone principally produced by the stomach, but also by numerous peripheral tissues including the placenta. Ghrelin acts via growth hormone secretagogue receptors (GHSR-1a) to alter food intake, fat utilization, and cellular proliferation, and has been suggested to play a role in the developmental growth of the fetoplacental unit. The placental expression of ghrelin and its role in ruminant species is not known. We tested the hypotheses that ghrelin and its functional receptor, GHSR-1a, are present in tissues of the ovine placenta, and that their expression is linked to the stage of development.</p> <p>Methods</p> <p>Antibodies raised against ghrelin and GHSR-1a were used in standard immunohistochemical protocols on placental tissues collected from pregnant ewes (n = 6 per gestational time point) at days 50, 80, 100, 128 and 135 of gestation (term ≈ day 145). Immunostaining for ghrelin and GHSR-1a was quantified using computer-aided image analysis. Image analysis data were subjected to one-way ANOVA, with differences in immunostaining between time-points determined by Fisher's least significant difference.</p> <p>Results</p> <p>Positive immunostaining for ghrelin was detected in ovine placentae at all gestational time points, with staining localized to the maternal epithelium, caruncle and trophectoderm. There was a significant effect of gestational age (p < 0.001) on the placental expression of ghrelin, with maximal levels at gestational day 80. GHSR-1a immunostaining was detected in the fetal trophectoderm at all time points. In contrast to the gestational pattern of ghrelin expression, there was no effect of gestational age on placental GHSR-1a immunoexpression.</p> <p>Conclusion</p> <p>Ghrelin and GHSR-1a are both present in the ovine placenta, and ghrelin displays a developmentally-related pattern of expression. Therefore, these data strongly suggest that the ghrelin system may have a role in feto-placental development in sheep.</p

Male Circumcision and STI Acquisition in Britain: Evidence from a National Probability Sample Survey.

BACKGROUND: It is well-established that male circumcision reduces acquisition of HIV, herpes simplex virus 2, chancroid, and syphilis. However, the effect on the acquisition of non-ulcerative sexually transmitted infections (STIs) remains unclear. We examined the relationship between circumcision and biological measures of three STIs: human papillomavirus (HPV), Chlamydia trachomatis and Mycoplasma genitalium. METHODS: A probability sample survey of 15,162 men and women aged 16-74 years (including 4,060 men aged 16-44 years) was carried out in Britain between 2010 and 2012. Participants completed a computer-assisted personal interview, including a computer-assisted self-interview, which asked about experience of STI diagnoses, and circumcision. Additionally, 1,850 urine samples from sexually-experienced men aged 16-44 years were collected and tested for STIs. Multivariable logistic regression was used to calculate adjusted odds ratios (AOR) to quantify associations between circumcision and i) self-reporting any STI diagnosis and ii) presence of STIs in urine, in men aged 16-44 years, adjusting for key socio-demographic and sexual behavioural factors. RESULTS: The prevalence of circumcision in sexually-experienced men aged 16-44 years was 17.4% (95%CI 16.0-19.0). There was no association between circumcision and reporting any previous STI diagnoses, and specifically previous chlamydia or genital warts. However, circumcised men were less likely to have any HPV type (AOR 0.26, 95% confidence interval (CI) 0.13-0.50) including high-risk HPV types (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and/or 68) (AOR 0.14, 95% CI 0.05-0.40) detected in urine. CONCLUSIONS: Circumcised men had reduced odds of HPV detection in urine. These findings have implications for improving the precision of models of STI transmission in populations with different circumcision prevalence and in designing interventions to reduce STI acquisition

Examining the association between male circumcision and sexual function: evidence from a British probability survey.

OBJECTIVE: Despite biological advantages of male circumcision in reducing HIV/sexually transmitted infection acquisition, concern is often expressed that it may reduce sexual enjoyment and function. We examine the association between circumcision and sexual function among sexually active men in Britain using data from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Natsal-3 asked about circumcision and included a validated measure of sexual function, the Natsal-SF, which takes into account not only sexual difficulties but also the relationship context and overall level of satisfaction. METHODS: A stratified probability survey of 6293 men and 8869 women aged 16-74 years, resident in Britain, undertaken 2010-2012, using computer-assisted face-to-face interviewing with computer-assisted self-interview for the more sensitive questions. Logistic regression was used to calculate odds ratios (ORs) to examine the association between reporting male circumcision and aspects of sexual function among sexually active men (n = 4816). RESULTS: The prevalence of male circumcision in Britain was 20.7% [95% confidence interval (CI): 19.3-21.8]. There was no association between male circumcision and, being in the lowest quintile of scores for the Natsal-SF, an indicator of poorer sexual function (adjusted OR: 0.95, 95% CI: 0.76-1.18). Circumcised men were as likely as uncircumcised men to report the specific sexual difficulties asked about in Natsal-3, except that a larger proportion of circumcised men reported erectile difficulties. This association was of borderline statistical significance after adjusting for age and relationship status (adjusted OR: 1.27, 95% CI: 0.99-1.63). CONCLUSION: Data from a large, nationally representative British survey suggest that circumcision is not associated with men's overall sexual function at a population level

Rab11-FIP3 is a cell cycle-regulated phosphoprotein

&lt;b&gt;BACKGROUND:&lt;/b&gt; Rab11 and its effector molecule, Rab11-FIP3 (FIP3), associate with recycling endosomes and traffic into the furrow and midbody of cells during cytokinesis. FIP3 also controls recycling endosome distribution during interphase. Here, we examine whether phosphorylation of FIP3 is involved in these activities.&lt;p&gt;&lt;/p&gt; &lt;b&gt;RESULTS:&lt;/b&gt; We identify four sites of phosphorylation of FIP3 in vivo, S-102, S-280, S-347 and S-450 and identify S-102 as a target for Cdk1-cyclin B in vitro. Of these, we show that S-102 is phosphorylated in metaphase and is dephosphorylated as cells enter telophase. Over-expression of FIP3-S102D increased the frequency of binucleate cells consistent with a role for this phospho-acceptor site in cytokinesis. Mutation of S-280, S-347 or S-450 or other previously identified phospho-acceptor sites (S-488, S-538, S-647 and S-648) was without effect on binucleate cell formation and did not modulate the distribution of FIP3 during the cell cycle. In an attempt to identify a functional role for FIP3 phosphorylation, we report that the change in FIP3 distribution from cytosolic to membrane-associated observed during progression from anaphase to telophase is accompanied by a concomitant dephosphorylation of FIP3. However, the phospho-acceptor sites identified here did not control this change in distribution.&lt;p&gt;&lt;/p&gt; &lt;b&gt;CONCLUSIONS:&lt;/b&gt; Our data thus identify FIP3 as a cell cycle regulated phosphoprotein and suggest dephosphorylation of FIP3 accompanies its translocation from the cytosol to membranes during telophase. S102 is dephosphorylated during telophase; mutation of S102 exerts a modest effect on cytokinesis. Finally, we show that de/phosphorylation of the phospho-acceptor sites identified here (S-102, S-280, S-347 and S-450) is not required for the spatial control of recycling endosome distribution or function

Assessing the sensitivity of information distortion to four potential influences in studies of risky choice

The emergence of a leading alternative during the course of a decision is known to bias the evaluation of new information in a manner that favors that alternative. We report 3 studies that address the sensitivity of predecisional information distortion and its effects in hypothetical risky decisions with regard to 4 potential influences: choice domain, repeated choice, memory requirements, and intermediate progress questions. In Experiment 1 (N = 515), the magnitude of information distortion was similar in 5 choice domains (varied between participants) involving monetary gambles, song downloads, frequent-flyer miles, political decisions, or medical decisions. Information distortion mediated the relationship between our manipulation of initial preferences and participants’ final choices, with the magnitude of the indirect effect being roughly similar across domains. These results replicate and extend previous findings. Additionally, distortion decreased significantly over 4 similar decision problems (within participants), but remained significant in the fourth problem. In Experiment 2 (N = 214), information distortion increased significantly when previously viewed information remained available, apparently because reiterating that information strengthened emerging preferences. In Experiment 3 (N = 223), the removal of intermediate progress questions that measure information distortion and emerging preferences did not significantly affect final choices, again replicating previous results. We conclude that predecisional information distortion is a relatively stable and robust phenomenon that deserves a prominent role in descriptive theories of choice

Adapted motivational interviewing to improve the uptake of treatment for glaucoma in Nigeria: study protocol for a randomized controlled trial.

BACKGROUND: Glaucoma is a chronic eye disease associated with irreversible visual loss. In Africa, glaucoma patients often present late, with very advanced disease. One-off procedures, such as laser or surgery, are recommended in Africa because of lack of or poor adherence to medical treatment. However, acceptance of surgery is usually extremely low. To prevent blindness, adherence to treatment needs to improve, using acceptable, replicable and cost-effective interventions. After reviewing the literature and interviewing patients in Bauchi (Nigeria) motivational interviewing (MI) was selected as the intervention for this trial, with adaptation for glaucoma (MIG). MI is designed to strengthen personal motivation for, and commitment to a specific goal by eliciting and exploring a person's reasons for change within an atmosphere of acceptance and compassion. The aim of this study is to assess whether MIG increases the uptake of laser or surgery amongst glaucoma patients where this is the recommended treatment. The hypothesis is that MIG increases the uptake of treatment. This will be the first trial of MI in Africa. METHODS: This is a hospital based, single centre, randomized controlled trial of MIG plus an information sheet on glaucoma and its treatment (the latter being "standard care") compared with standard care alone for glaucoma patients where the treatment recommended is surgery or laser.Those eligible for the trial are adults aged 17 years and above who live within 200 km of Bauchi with advanced glaucoma where the examining ophthalmologist recommends surgery or laser. After obtaining written informed consent, participants will be randomly allocated to MIG plus standard care, or standard care alone. Motivational interviewing will be delivered in Hausa or English by one of two MIG trained personnel. One hundred and fifty participants will be recruited to each arm. The primary outcome is the proportion of participants undergoing laser or surgery within two months of the date given to re attend for the procedure. MIG quality will be assessed using the validated MI treatment integrity scale. DISCUSSION: Motivational interviewing may be an important tool to increase the acceptance of treatment for glaucoma. The approach is potentially scalable and may be useful for other chronic conditions in Africa. TRIAL REGISTRATION: ISRCTN79330571 (Controlled-Trials.com)

Latent cluster analysis of ALS phenotypes identifies prognostically differing groups

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes. METHODS Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method. RESULTS The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001). Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb) and time from symptom onset to diagnosis (p<0.00001). CONCLUSION The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research

Cell-Nanoparticle Interactions at (Sub)-Nanometer Resolution Analyzed by Electron Microscopy and Correlative Coherent Anti-Stokes Raman Scattering

A wide variety of nanoparticles are playing an increasingly important role in drug delivery. Label-free imaging techniques are especially desirable to follow the cellular uptake and intracellular fate of nanoparticles. The combined correlative use of different techniques, each with unique advantages, facilitates more detailed investigation about such interactions. The synergistic use of correlative coherent anti-Stokes Raman scattering and electron microscopy (C-CARS-EM) imaging offers label-free, chemically-specific, and (sub)-nanometer spatial resolution for studying nanoparticle uptake into cells as demonstrated in the current study. Coherent anti-Stokes Raman scattering (CARS) microscopy offers chemically-specific (sub)micron spatial resolution imaging without fluorescent labels while transmission electron microscopy (TEM) offers (sub)-nanometer scale spatial resolution and thus visualization of precise nanoparticle localization at the sub-cellular level. This proof-of-concept imaging platform with unlabeled drug nanocrystals and macrophage cells revealed good colocalization between the CARS signal and electron dense nanocrystals in TEM images. The correlative TEM images revealed subcellular localization of nanocrystals inside membrane bound vesicles, showing multivesicular body (MVB)-like morphology typical for late endosomes (LEs), endolysosomes, and phagolysosomes. C-CARS-EM imaging has much potential to study the interactions between a wide range of nanoparticles and cells with high precision and confidence.Peer reviewe

A model for the waveform behavior of accreting millisecond pulsars: Nearly aligned magnetic fields and moving emission regions

We investigate further a model of the accreting millisecond X-ray pulsars we proposed earlier. In this model, the X-ray-emitting regions of these pulsars are near their spin axes but move. This is to be expected if the magnetic poles of these stars are close to their spin axes, so that accreting gas is channeled there. As the accretion rate and the structure of the inner disk vary, gas is channeled along different field lines to different locations on the stellar surface, causing the X-ray-emitting areas to move. We show that this "nearly aligned moving spot model" can explain many properties of the accreting millisecond X-ray pulsars, including their generally low oscillation amplitudes and nearly sinusoidal waveforms; the variability of their pulse amplitudes, shapes, and phases; the correlations in this variability; and the similarity of the accretion- and nuclear-powered pulse shapes and phases in some. It may also explain why accretion-powered millisecond pulsars are difficult to detect, why some are intermittent, and why all detected so far are transients. This model can be tested by comparing with observations the waveform changes it predicts, including the changes with accretion rate.Comment: 21 pages, 6 figures; includes 3 new sections, 14 additional pages, 4 additional figures with 11 new plots, and additional references; accepted for publication in Ap

Habilitation provision for children and young people with vision impairment in the United Kingdom: A lack of clarity leading to inconsistencies

The key to empowering and supporting children and young people (CYP) with vision impairment (VI) to achieve their potential lies in the delivery of habilitation training. Evidence has revealed that provision of habilitation services across the United Kingdom was inconsistent, with CYP with VI not receiving services in some areas. This research explored the accessibility and quality of habilitation provision for CYP with VI via two studies: (1) 12 qualitative case studies of habilitation practice and (2) surveys of habilitation training experiences, with CYP with VI (n = 43) and with parents of CYP with VI (n = 68). Five themes were identified highlighting inconsistencies and variability in the delivery of habilitation training in recent years, a lack of focus on independent living skills training, on social inclusion and emotional well-being, a lack of support for parents and a lack of clarity with regard to the definition of habilitation, and who is responsible for providing training