The Impact of Shame on the Therapeutic Alliance and Intimate Relationships

Objectives


This study examined the role of shame coping styles and state shame in predicting the therapeutic alliance and intimate relationship functioning in individuals with mental health problems.


Method


A sample of 50 treatment-receiving adults aged 21 to 67 years with a mix of common mental health difficulties was recruited from a clinical psychology service. Participants were given questionnaire measures of shame states, shame coping styles, intimate relationship functioning, and the therapeutic alliance.


Results


Regression analyses indicated that the shame coping strategy of physical and psychological withdrawal was the primary risk factor for development of a less effective therapeutic alliance. Both withdrawal and attack self coping styles were significant predictors of impaired intimate relationship functioning.


Conclusions


These findings have implications for the theoretical role of shame in mental health presentations as well as the potential for internalizing shame coping styles (i.e., withdrawal, attack self) to act as a barrier to successful therapy and interpersonal relationships. The inclusion of shame-focused assessments and interventions in the initial stages of treatment with clients exhibiting these strategies could improve prognosis.

In vivo tropism of attenuated and pathogenic measles virus expressing green fluorescent protein in macaques

The global increase in measles vaccination has resulted in a significant reduction of measles mortality. The standard route of administration for the live-attenuated measles virus (MV) vaccine is subcutaneous injection, although alternative needle-free routes, including aerosol delivery, are under investigation. In vitro, attenuated MV has a much wider tropism than clinical isolates, as it can use both CD46 and CD150 as cellular receptors. To compare the in vivo tropism of attenuated and pathogenic MV, we infected cynomolgus macaques with pathogenic or attenuated recombinant MV expressing enhanced green fluorescent protein (GFP) (strains IC323 and Edmonston, respectively) via the intratracheal or aerosol route. Surprisingly, viral loads and cellular tropism in the lungs were similar for the two viruses regardless of the route of administration, and CD11c-positive cells were identified as the major target population. However, only the pathogenic MV caused significant viremia, which resulted in massive virus replication in B and T lymphocytes in lymphoid tissues and viral dissemination to the skin and the submucosa of respiratory epithelia. Attenuated MV was rarely detected in lymphoid tissues, and when it was, only in isolated infected cells. Following aerosol inhalation, attenuated MV was detected at early time points in the upper respiratory tract, suggesting local virus replication. This contrasts with pathogenic MV, which invaded the upper respiratory tract only after the onset of viremia. This study shows that despite in vitro differences, attenuated and pathogenic MV show highly similar in vivo tropism in the lungs. However, systemic spread of attenuated MV is restricted.

Recent mumps outbreaks in vaccinated populations: no evidence of immune escape.

Recently, numerous large-scale mumps outbreaks have occurred in vaccinated populations. Clinical isolates sequenced from these outbreaks have invariably been of genotypes distinct from those of vaccine viruses, raising concern that certain mumps virus strains may escape vaccine-induced immunity. To investigate this concern, sera obtained from children 6 weeks after receipt of measles, mumps, and rubella (MMR) vaccine were tested for the ability to neutralize a carefully selected group of genetically diverse mumps virus strains. Although the geometric mean neutralizing antibody titer of the sera was lower against some virus strains than others, all viruses were readily neutralized, arguing against immune escape.

The Hekla 1947 tephra in the North of Ireland: regional distribution, concentration and geochemistry.

A cryptotephra layer from the eruption of Hekla in 1947 has recently been discovered in Irish peatlands. This tephra layer represents the most recent deposition of volcanic ash in the UK prior to the eruption of Eyjafjallajökull in 2010. Here we examine the concentration and geochemistry of the Hekla 1947 tephra in 14 peat profiles from across Northern Ireland. Electron probe microanalysis of individual tephra shards (n?=?91) reveals that the tephra is of dacitic–andesitic geochemistry and is highly similar to the Hekla 1510 tephra, although spheroidal carbonaceous particle profiles can be used for successful discrimination of the two layers. The highest concentrations of Hekla 1947 are found in western sites, probably reflecting the pathway of the ash fall event due to the prevailing wind direction. Comparable tephra concentrations from two cores (1?km apart) from a single bog and from nearby sites may suggest that tephra shard concentrations in peat profiles reflect ash fallout densities across a specific region, rather than site-specific factors associated with peatlands. This paper firmly establishes Hekla 1947 as a useful chronostratigraphic marker for the twentieth century, although within a restricted zone.

Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes

A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future.

Production and Evaluation of Antibodies and Phage Display-Derived Peptide Ligands for Immunomagnetic Separation of Mycobacterium bovis

This study describes the development and optimization of an immunomagnetic separation (IMS) method to isolate Mycobacterium bovis cells from lymph node tissues. Gamma-irradiated whole M. bovis AF2122/97 cells and ethanol-extracted surface antigens of such cells were used to produce M. bovis-speci?c polyclonal and monoclonal antibodies in rabbits and mice. They were also used to generate M. bovis-speci?c peptide ligands by phage display biopanning. The various antibodies and peptide ligands obtained were used to coat MyOne tosyl-activated Dynabeads (Life Technologies), singly or in combination, and evaluated for IMS. Initially, M. bovis capture from Middlebrook 7H9 broth suspensions (concentration range, 10 to 10⁵ CFU/ml) was evaluated by IMS combined with an M. bovis-speci?c touchdown PCR. IMS-PCR results and, subsequently, IMS-culture results indicated that the beads with greatest immunocapture capability for M. bovis in broth were those coated simultaneously with a monoclonal antibody and a biotinylated 12-mer peptide. These dually coated beads exhibited minimal capture (mean of 0.36% recovery) of 12 other Mycobacterium spp. occasionally encountered in veterinary tuberculosis (TB) diagnostic laboratories. When the optimized IMS method was applied to various M. bovis-spiked lymph node matrices, it demonstrated excellent detection sensitivities (50% limits of detection of 3.16 and 57.7 CFU/ml of lymph node tissue homogenate for IMS-PCR and IMS-culture, respectively). The optimized IMS method therefore has the potential to improve isolation of M. bovis from lymph nodes and hence the diagnosis of bovine tuberculosis.

Sustained Release of the CCR5 Inhibitors CMPD167 and Maraviroc from Vaginal Rings in Rhesus Macaques

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for prevention of sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of the entry inhibitors maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously over 28 days from rings in vitro, at rates of 100-2500 µg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady state fluid concentrations were ~106 fold greater than IC50 values for SHIV-162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. Pretreatment of macaques with Depo-Provera® (DP), as commonly used in macaque challenge studies, was shown to significantly modify the bio-distribution of the inhibitors, but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments, and also for ring performance during the human female menstrual cycle. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

Multiple site dioxygenase-catalysed cis-dihydroxylation of polycyclic azaarenes to yield a new class of bis-cis-diol metabolites

The enhanced stability of new mono-cis-dihydrodiol bacterial metabolites of tricyclic azaarenes has facilitated the dioxygenase-catalysed formation and isolation of the corresponding bis-cis-dihydrodiols (cis-tetraols) and a three step chemoenzymatic route to the derived arene oxide mammalian metabolites.

Correlating Alpine glaciation with Adriatic sea-level changes through lake and alluvial stratigraphy

We compare lake and alluvial stratigraphy along a frame connecting the southern Alpine foothills and the Adriatic Sea, with the aim of matching the effects of Alpine glaciation and sea-level changes on sedimentation during the last glacial cycle. The palynostratigraphy of Lake Fimon provided proxies for regional vegetation and climate change and was coupled with sediment petrography, loss on ignition and magnetic susceptibility, disentangling alluvial phases from fluvioglacial activity related to culminations of the southeastern Alpine glaciers. The Fimon area was not reached by alluvial fans during the penultimate glacial maximum, nor by the sea transgression during the last interglacial, but a closed lake soon developed at the Eemian onset due to enhanced rainfall. Sea-level fall at glacial inception triggered the entrenchment of the drainage network in the plain reaching the outer Fimon Basin. Slow aggradation, but no sign of fluvioglacial activity, lasted to 38.2 +/- 1.45 cal. ka BP, when a major forest withdrawal took place, coeval to the spread of alluvial fans. By 27.5 perpendicular to 0.5 cal. ka BP the Fimon Basin was dammed by the Brenta outwash system. The main step of of forest recovery commenced at around (15.8) cal. ka BP, when apex trenching of the outwash fans was triggered by the glacier's decay. Copyright (C) 2011 John Wiley & Sons, Ltd.

Self-reported medication non-compliance in the elderly

Objective: To assess self-reported compliance with prescribed medications in a population of elderly patients prior to their hospital admission in an attempt to understand further the factors which influence drug taking patterns.

‘”Like an Old Cathedral City”: Belfast Welcomes Queen Victoria, August 1849’,

Belfast, with its history of communal violence, is normally seen as lying outside the mainstream of nineteenth-century British urban development. The visit of Queen Victoria in 1849 suggests a more complex, less linear picture. What emerges is an urban identity in transition, in which aspirations to conform to an ideal of civic harmony temporarily overrode acute sectarian and political divisions, where pride in recent economic achievement sat uneasily alongside an awareness of the town’s newcomer status, and where an emerging sense of regional difference competed with a continuing assumption of Irish identity.