Genetic Research and Women’s Heart Disease: a Primer

PURPOSE OF REVIEW: This review provides a brief synopsis of sexual dimorphism in atherosclerosis with an emphasis on genetic studies aimed to better understand the atherosclerotic process and clinical outcomes in women. Such studies are warranted because development of atherosclerosis, impact of several traditional risk factors, and burden of coronary heart disease (CHD) differ between women and men. RECENT FINDINGS: While most candidate gene studies pool women and men and adjust for sex, some sex-specific studies provide evidence of association between candidate genes and prevalent and incident CHD in women. So far, most genome-wide association studies (GWAS) also failed to consider sex-specific associations. The few GWAS focused on women tended to have small sample sizes and insufficient power to reject the null hypothesis of no association even if associations exist. SUMMARY: Few studies consider that sex can modify the effect of gene variants on CHD. Sufficiently large-scale genetic studies in women of different race/ethnic groups, taking into account possible gene-gene and gene-environment interactions as well as hormone-mediated epigenetic mechanisms, are needed. Using the same disease definition for women and men might not be appropriate. Accurate phenotyping and inclusion of relevant outcomes in women, together with targeting the entire spectrum of atherosclerosis, could help address the contribution of genes to sexual dimorphism in atherosclerosis. Discovered genetic loci should be taken forward for replication and functional studies to elucidate the plausible underlying biological mechanisms. A better understanding of the etiology of atherosclerosis in women would facilitate future prevention efforts and interventions

Should mentoring be routinely introduced into general dental practice to reduce the risk of occupational stress?

Introduction: Occupational stress within general dental practice can potentially have an adverse impact on a practitioner's wellbeing and the quality of healthcare provided by that individual. Mentoring has routinely been utilised in other professions for stress management, however, there is little in the dental literature discussing the benefits of mentorship on the reduction of occupational stress for dental practitioners. Aim: The aim of this study was to explore the perceptions of experienced foundation dental trainers within the Health Education, Kent, Surrey and Sussex postgraduate deanery as to the usefulness of routine mentoring as a tool to reduce occupational stress. Methods: Using a qualitative approach, six individual semi-structured interviews were undertaken. Recorded interviews were transcribed and transcriptions were analysed using thematic coding to identify overarching themes. Results: Both similarities and differences with the existing literature on routine mentoring within professional settings were identified. Foundation dental trainers were positive towards the concept of routine mentoring, although there was also a degree of scepticism regarding the potential uptake among colleagues. There was a perception that mentoring might more practically be used as a reactionary tool. Multiple potential barriers to routine mentoring were identified, included funding, scheduling and a lack of training. Conclusions: The analysis identified that currently, experienced foundation dental practitioners do not consider routine mentoring as a practical option in the prevention of occupational stress. The results would suggest that further education is required as to the benefits of routine mentoring as a strategy for occupational stress management. However, with additional resources buying time, a hybrid model of mentoring and coaching has significant potential in general dental practice

Proton and hydride transfers in solution: hybrid QMmm/MM free energy perturbation study

A hybrid quantum and molecular mechanical (QM/MM) free energy perturbation (FEP) method is implemented in the context of molecular dynamics (MD). The semiempirical quantum mechanical (QM) Hamiltonian (Austin Model 1) represents solute molecules, and the molecular mechanical (MM) CHARMM force field describes the water solvent. The QM/MM FEP method is used to calculate the free energy changes in aqueous solution for (1) a proton transfer from methanol to imidazole and (2) a hydride transfer from methoxide to nicotinamide. The QM/MM interaction energies between the solute and solvent arc calibrated to emulate the solute-solvent interaction energies determined at the Hartee-Fock 6-31G(d) level of ab initio theory. The free energy changes for the proton and hydride transfers are calculated to be 15.1 and {minus}6.3 kcal/mol, respectively, which compare favorably with the corresponding experimental values of 12.9 and {minus}7.4 kcal/mol. An estimate of the reliability of the calculations is obtained through the computation of the forward (15.1 and {minus}6.3 kcal/mol) and backward ({minus}14.1 and 9.1 kcal/mol)free energy changes. The reasonable correspondence between these two independent calculations suggests that adequate phase space sampling is obtained along the reaction pathways chosen to transform the proton and hydride systems between their respective reactant and product states

On the Quantum Invariant for the Spherical Seifert Manifold

We study the Witten--Reshetikhin--Turaev SU(2) invariant for the Seifert manifold $S^3/\Gamma$ where $\Gamma$ is a finite subgroup of SU(2). We show that the WRT invariants can be written in terms of the Eichler integral of the modular forms with half-integral weight, and we give an exact asymptotic expansion of the invariants by use of the nearly modular property of the Eichler integral. We further discuss that those modular forms have a direct connection with the polyhedral group by showing that the invariant polynomials of modular forms satisfy the polyhedral equations associated to $\Gamma$.Comment: 36 page

Observations on the pathology of canine microsporidiosis

The available literature on canine microsporidiosis indicates that this disease, primarily of young dogs, is a distinct clinicopathological entity. It has been confused with canine distemper and rabies, and must be differentiated from toxoplasmosis. Information available on the spectrum of pathological change associated with this disease is incomplete but a distinct pattern emerges from a study of the reports. The aetiological agent appears to have a predilection for the central nervous system and kidneys, but other tissues and organs, and especially the liver, may also be infected. Vasculitis and perivasculitis, which may include fibrinoid necrosis, seem to be a basic lesion. Cellular inflammation ranges from polymorphonuclear leukocyte infiltration in areas of necrosis to focal granulomas. There may be no cellular reaction to compact groups of organisms. Histopathological and ultrastructural studies of this case augment our knowledge of the pathological changes seen with canine microsporidiosis.The articles have been scanned in colour with a HP Scanjet 5590; 300dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

The consequences of ubiquitous expression of the wingless gene in the Drosophila embryo

The segment polarity gene wingless has an essential function in cell-to-cell communication during various stages of Drosophila development. The wingless gene encodes a secreted protein that affects gene expression in surrounding cells but does not spread far from the cells where it is made. In larvae, wingless is necessary to generate naked cuticle in a restricted part of each segment. To test whether the local accumulation of wingless is essential for its function, we made transgenic flies that express wingless under the control of a hsp70 promoter (HS-wg flies). Uniform wingless expression results in a complete naked cuticle, uniform armadillo accumulation and broadening of the engrailed domain. The expression patterns of patched, cubitus interruptus Dominant and Ultrabithorax follow the change in engrailed. The phenotype of heatshocked HS-wg embryos resembles the segment polarity mutant naked, suggesting that embryos that overexpress wingless or lack the naked gene enter similar developmental pathways. The ubiquitous effects of ectopic wingless expression may indicate that most cells in the embryo can receive and interpret the wingless signal. For the development of the wild-type pattern, it is required that wingless is expressed in a subset of these cells

Multiresolution analysis of active region magnetic structure and its correlation with the Mt. Wilson classification and flaring activity

Two different multi-resolution analyses are used to decompose the structure of active region magnetic flux into concentrations of different size scales. Lines separating these opposite polarity regions of flux at each size scale are found. These lines are used as a mask on a map of the magnetic field gradient to sample the local gradient between opposite polarity regions of given scale sizes. It is shown that the maximum, average and standard deviation of the magnetic flux gradient for alpha, beta, beta-gamma and beta-gamma-delta active regions increase in the order listed, and that the order is maintained over all length-scales. This study demonstrates that, on average, the Mt. Wilson classification encodes the notion of activity over all length-scales in the active region, and not just those length-scales at which the strongest flux gradients are found. Further, it is also shown that the average gradients in the field, and the average length-scale at which they occur, also increase in the same order. Finally, there are significant differences in the gradient distribution, between flaring and non-flaring active regions, which are maintained over all length-scales. It is also shown that the average gradient content of active regions that have large flares (GOES class 'M' and above) is larger than that for active regions containing flares of all flare sizes; this difference is also maintained at all length-scales.Comment: Accepted for publication in Solar Physic

Effects of unidirectional flow shear stresses on the formation, fractal microstructure and rigidity of incipient whole blood clots and fibrin gels

Incipient clot formation in whole blood and fibrin gels was studied by the rheometric techniques of controlled stress parallel superposition (CSPS) and small amplitude oscillatory shear (SAOS). The effects of unidirectional shear stress on incipient clot microstructure, formation kinetics and elasticity are reported in terms of the fractal dimension (df ) of the fibrin network, the gel network formation time (TGP ) and the shear elastic modulus, respectively. The results of this first haemorheological application of CSPS reveal the marked sensitivity of incipient clot microstructure to physiologically relevant levels of shear stress, these being an order of magnitude lower than have previously been studied by SAOS. CSPS tests revealed that exposure of forming clots to increasing levels of shear stress produces a corresponding elevation in df , consistent with the formation of tighter, more compact clot microstructures under unidirectional flow. A corresponding increase in shear elasticity was recorded. The scaling relationship established between shear elasticity and df for fibrin clots and whole blood confirms the fibrin network as the dominant microstructural component of the incipient clot in terms of its response to imposed stress. Supplementary studies of fibrin clot formation by rheometry and microscopy revealed the substantial additional network mass required to increase df and provide evidence to support the hypothesis that microstructural changes in blood clotted under unidirectional shear may be attributed to flow enhanced thrombin generation and activation. CSPS also identified a threshold value of unidirectional shear stress above which no incipient clot formation could be detected. CSPS was shown to be a valuable haemorheological tool for the study of the effects of physiological and pathological levels of shear on clot properties

A mechanism for morphogen-controlled domain growth

Many developmental systems are organised via the action of graded distributions of morphogens. In the Drosophila wing disc, for example, recent experimental evidence has shown that graded expression of the morphogen Dpp controls cell proliferation and hence disc growth. Our goal is to explore a simple model for regulation of wing growth via the Dpp gradient: we use a system of reaction-diffusion equations to model the dynamics of Dpp and its receptor Tkv, with advection arising as a result of the flow generated by cell proliferation. We analyse the model both numerically and analytically, showing that uniform domain growth across the disc produces an exponentially growing wing disc