Stigma, social appearance anxiety and coping in men and women living with skin conditions: A mixed methods analysis.

Background: The psychological impact of living with a skin condition can have a profound impact on quality of life and could cause appearance-related social anxiety. Existing research suggests ambiguous findings in relation to whether the impact of living with a skin condition differs between males and females. Objectives: The present study aimed to explore the association between stigma, coping styles and social appearance anxiety in men and women living with a skin condition in the United Kingdom. Methods: 231 participants (n = 199 females, n = 30 males, n = 2 non-binary) completed a cross-sectional online questionnaire, capturing quantitative data with the social appearance anxiety scale (SAAS), the shortened version of the coping inventory for stressful situations (CISS-21), and qualitative data from free-text comments and thematic content analysis. Respondents were also asked to provide additional free text comments in relation to the challenges faced and how these were managed. Results: Content analysis revealed that males and females faced daily practical, social and emotional challenges and coped with them in several ways; with higher levels of social appearance anxiety associated with both higher perceived severity of skin condition and younger age. Males and females appeared equally as emotionally affected by living with a skin condition, with the only significant gender difference being females as significantly more likely to engage in avoidant coping behaviours than males. Conclusions: Living with a skin condition presents daily practical, social, and psychological challenges for males and females that have the potential to impact on quality of life. Findings highlight the need for dermatological care to routinely address these issues, and psychosocial interventions must be made available to promote healthy coping with skin conditions.

How useful are port surveys focused on target pest identification for exotic species management?

Monitoring surveys are an important tool for detecting new arrivals of exotic species, for documenting patterns of invasion, and exotic species impacts. Faced with time and cost constraints, these surveys are increasingly focused on lists of target pest species, identified as being most likely to arrive and cause significant harm. We used the national survey of Australian international ports for introduced marine pests as a case study to assess: (1) the taxonomic rigor of surveys focused on detection of target species; and (2) how the ability of port surveys to inform invasion patterns is dependent on taxonomic approach. Our analysis of the 46 available reports revealed common sub-optimal taxonomic practices that compromised their utility to identify abiotic conditions that are good predictors of biological invasion. Thus, although surveys for target species may provide information on the distribution of a handful of species, they may fail to do much else.

ENCORE: the effect of nutrient enrichment on coral reefs. Synthesis of results and conclusions.

Coral reef degradation resulting from nutrient enrichment of coastal waters is of increasing global concern. Although effects of nutrients on coral reef organisms have been demonstrated in the laboratory, there is little direct evidence of nutrient effects on coral reef biota in situ. The ENCORE experiment investigated responses of coral reef organisms and processes to controlled additions of dissolved inorganic nitrogen (N) and/or phosphorus (P) on an offshore reef (One Tree Island) at the southern end of the Great Barrier Reef, Australia. A multi-disciplinary team assessed a variety of factors focusing on nutrient dynamics and biotic responses. A controlled and replicated experiment was conducted over two years using twelve small patch reefs ponded at low tide by a coral rim. Treatments included three control reefs (no nutrient addition) and three + N reefs (NH4Cl added), three + P reefs (KH2PO4 added), and three + N + P reefs. Nutrients were added as pulses at each low tide (ca twice per day) by remotely operated units. There were two phases of nutrient additions. During the initial, low-loading phase of the experiment nutrient pulses (mean dose = 11.5 microM NH4+; 2.3 microM PO4(-3)) rapidly declined, reaching near-background levels (mean = 0.9 microM NH4+; 0.5 microM PO4(-3)) within 2-3 h. A variety of biotic processes, assessed over a year during this initial nutrient loading phase, were not significantly affected, with the exception of coral reproduction, which was affected in all nutrient treatments. In Acropora longicyathus and A. aspera, fewer successfully developed embryos were formed, and in A. longicyathus fertilization rates and lipid levels decreased. In the second, high-loading, phase of ENCORE an increased nutrient dosage (mean dose = 36.2 microM NH4+; 5.1 microM PO4(-3)) declining to means of 11.3 microM NH4+ and 2.4 microM PO4(-3) at the end of low tide) was used for a further year, and a variety of significant biotic responses occurred. Encrusting algae incorporated virtually none of the added nutrients. Organisms containing endosymbiotic zooxanthellae (corals and giant clams) assimilated dissolved nutrients rapidly and were responsive to added nutrients. Coral mortality, not detected during the initial low-loading phase, became evident with increased nutrient dosage, particularly in Pocillopora damicornis. Nitrogen additions stunted coral growth, and phosphorus additions had a variable effect. Coral calcification rate and linear extension increased in the presence of added phosphorus but skeletal density was reduced, making corals more susceptible to breakage. Settlement of all coral larvae was reduced in nitrogen treatments, yet settlement of larvae from brooded species was enhanced in phosphorus treatments. Recruitment of stomatopods, benthic crustaceans living in coral rubble, was reduced in nitrogen and nitrogen plus phosphorus treatments. Grazing rates and reproductive effort of various fish species were not affected by the nutrient treatments. Microbial nitrogen transformations in sediments were responsive to nutrient loading with nitrogen fixation significantly increased in phosphorus treatments and denitrification increased in all treatments to which nitrogen had been added. Rates of bioerosion and grazing showed no significant effects of added nutrients. ENCORE has shown that reef organisms and processes investigated in situ were impacted by elevated nutrients. Impacts were dependent on dose level, whether nitrogen and/or phosphorus were elevated and were often species-specific. The impacts were generally sub-lethal and subtle and the treated reefs at the end of the experiment were visually similar to control reefs. Rapid nutrient uptake indicates that nutrient concentrations alone are not adequate to assess nutrient condition of reefs. Sensitive and quantifiable biological indicators need to be developed for coral reef ecosystems. The potential bioindicators identified in ENCORE should be tested in future research on coral reef/nutrient interactions. Synergistic and cumulative effects of elevated nutrients and other environmental parameters, comparative studies of intact vs. disturbed reefs, offshore vs. inshore reefs, or the ability of a nutrient-stressed reef to respond to natural disturbances require elucidation. An expanded understanding of coral reef responses to anthropogenic impacts is necessary, particularly regarding the subtle, sub-lethal effects detected in the ENCORE studies.

Role of MHC class I expression and CD8(+) T cells in the evolution of iodine-induced thyroiditis in NOD-H2(h4) and NOD mice.

Dietary iodine has long been known to influence the development of human autoimmune thyroid disease. In nonobese diabetic (NOD) and NOD-H2(h4) mice elevated dietary iodine has been shown to induce autoimmune thyroid disease. Immune responses to thyroid antigens can be detected in these mouse strains, including T cell responses in the NOD-H2(h4) mouse to thyroid peroxidase. Cell transfer studies and antibody depletion experiments reveal a requirement for both CD4(+) T cells and CD8(+) T cells in the development of thyroid autoimmunity. Histological analyses of the thyroids show that following 1 week of iodine administration MHC class I expression is elevated on thyroid follicular cells and CD4(+) and CD8(+) T cells have begun to infiltrate the gland. Although MHC class II expression on thyroid epithelial cells was also elevated, the tempo of expression was slower and the extent of expression was far less than that for MHC class I. Depletion of CD8(+) T cells at early stages of disease induction inhibited not only thyroid infiltration and autoantibody production but also reduced the levels of MHC expression in the thyroid, suggesting that cytokine production by infiltrating lymphocytes was responsible for the increased MHC expression.

Peptides derived from murine insulin are diabetogenic in both rats and mice, but the disease-inducing epitopes are different: evidence against a common environmental cross-reactivity in the pathogenicity of type 1 diabetes.

Two rodent models of autoimmune type 1 diabetes have been used to investigate the role of insulin as an autoantigen in this disease. In lymphopoenia-induced diabetes in the PVG.RT1u rat, neonatal tolerization with insulin B-chain peptides, but not A-chain peptides, conferred significant protection from disease. After rechallenge of adult rats, neonatally B-chain-tolerized animals showed diminished B-chain-specific T-cell proliferation, interleukin (IL)-2 production, and interferon-gamma (IFN-gamma) production, as compared with control animals. The epitope recognized by the PVG.RT1u rat was mapped to residues 1-18 of the B-chain; T-cell lines specific for this epitope were generated, and these conferred diabetes upon adoptive transfer to irradiated syngeneic recipients. In adult nonobese diabetic (NOD) mice, subcutaneous immunization with B-chain peptide 9-23 emulsified in incomplete Freund's adjuvant (IFA) was also potent at preventing onset of diabetes. In contrast to PVG.RT1u rats, NOD mice recognized an epitope within residues 10-29 of the insulin B-chain. The data implicate insulin as a target autoantigen in type 1 diabetes but do not support a role for molecular mimicry to insulin in the pathogenesis of this disease.

The involvement of IL-12 in murine experimentally induced autoimmune thyroid disease.

Experimental autoimmune thyroid disease (EAT) can be induced experimentally in mice following immunization with mouse thyroglobulin (mTg) and the adjuvants lipopolysaccharide (LPS) or complete Freund's adjuvant (CFA). EAT can also be transferred to naive recipients by CD4+ T cells from mTg-primed mice. Here we demonstrate a role for IL-12 in the development of EAT by the ability of neutralizing antibody to IL-12 to reduce disease severity and by the lack of significant levels of thyroid infiltration in IL-12p40-deficient mice following immunization with mTg and CFA. A single injection of 300 ng IL-12 at the time of initial immunization with mTg and LPS was able to increase the degree of thyroid infiltration. These data are all consistent with EAT being a Th1-mediated disease. Conversely, however, administration of IL-12 over a prolonged period markedly inhibited the induction of EAT by mTg and CFA and, if given to recipients, inhibited the transfer of EAT by mTg-primed lymph node cells. The development of an autoantibody response to mTg was also inhibited when IL-12 was administered throughout the experimental period, suggesting that sustained exposure to IL-12 can be immunosuppressive.

Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice.

The spontaneous development of insulin dependent diabetes mellitus in non-obese diabetic (NOD) mice has been shown to be mediated by a Th1 response against beta cell antigens. It is known that in murine models of Schistosoma mansoni infection, egg production is associated with a switch from a Th1 to Th2 response. This subsequent dominance of a Th2 response in S.mansoni infected mice has been shown to influence the response to other infectious agents or antigens. We therefore determined whether infection with S.mansoni could influence the spontaneous incidence of insulin dependent diabetes mellitus (IDDM) in NOD mice. Infection with this helminth significantly reduced the spontaneous incidence of IDDM. IDDM was also prevented by injecting parasite eggs alone. Because until relatively recently humans might expect to succumb to a variety of infectious agents, the current freedom from infection might permit the expression of a genetic predisposition to autoimmune pathology and be responsible for the increased incidence of IDDM.

Effect of the synthetic immunomodulator, linomide, on experimental models of thyroiditis.

The drug Linomide is an immunomodulator showing marked down-regulation of several experimental autoimmune diseases. In this study, its effect on three different experimental models of thyroid disease and on spontaneous infiltration of salivary glands (sialoadenitis), was investigated. Although very effective at preventing thyroid infiltrates in mice immunized with mouse thyroglobulin and complete Freund's adjuvant and in spontaneous models of thyroiditis and sialoadenitis, it completely failed to modify experimental autoimmune thyroiditis (EAT) induced in mice immunized with mouse thyroglobulin and lipopolysaccharide. There was no significant shift in the observed isotypes of anti-mouse thyroglobulin antibodies and only anti-mouse thyroglobulin antibodies in the spontaneous model were completely down-modulated by the drug. One surprising fact to emerge was that Linomide-treated donor mice, although protected from thyroid lesions themselves, were still able to transfer EAT showing that they must have been effectively primed while being treated with Linomide. It is possible that the drug down modulated EAT by interfering with the trafficking of primed effector cells.

Both CD4(+) T cells and CD8(+) T cells are required for iodine accelerated thyroiditis in NOD mice.

The nonobese diabetic (NOD) mouse, a spontaneous animal model for insulin-dependent diabetes mellitus, displays a tendency in common with human diabetic populations to develop autoimmune thyroiditis although incidence and severity of thyroid lesions vary widely among different colonies around the world. A congenic strain of NOD mice bearing I-Ak on a NOD background (NOD-H2(h4)) has recently been derived and displays a much greater tendency to develop thyroiditis and autoantibodies to mouse thyroglobulin (MTg) although it is free of diabetes. Both thyroid infiltrates and autoantibody formation are accelerated and enhanced in NOD-H2(h4) mice by increased iodine intake. The effect of increased iodine intake on NOD mice themselves has not been directly investigated although a recent study of these animals given high or low doses of iodine showed no follicular destruction unless the mice were first rendered goitrous by iodine deprivation. We found that dietary iodine increased both the incidence and the severity of thyroid lesions in our NOD mice although autoantibodies to MTg were absent. NOD background genes appear to be essential for the development of these lesions, which were maximal after 4 weeks of iodine administration and showed no significant regression when the iodine was stopped. Furthermore, our studies show for the first time that both CD4(+) and CD8(+) T cells are necessary for the development of this accelerated but essentially spontaneous murine thyroid disease.

Protection from insulin dependent diabetes mellitus afforded by insulin antigens in incomplete Freund's adjuvant depends on route of administration.

Several islet antigens have been shown to modify the time of onset and severity of spontaneous insulin dependent diabetes mellitus (IDDM) in NOD (non-obese diabetic) mice. Oral, intravenous and intra-nasal administration of insulin and glutamic acid decarboxylase (GAD) or their derived peptides have all been shown to be effective to differing degrees in reducing the incidence and delaying the onset of diabetes in this mouse model of the disease. Incomplete Freund's Adjuvant (IFA) has also played a key role in tolerance when co-administered with insulin peptides subcutaneously. We show that route of administration may be of crucial importance, since although insulin B chain and the B9-23 peptide given in IFA subcutaneously protected (either partially or completely) from IDDM, when given intraperitoneally they completely failed to modify the disease.

Effect of MHC transgene expression on spontaneous insulin autoantibody class switch in nonobese diabetic mice.

A study of spontaneous anti-insulin autoantibodies in nonobese diabetic (NOD) mice revealed that when first detected, the antibodies are immunoglobulin M (IgM), but by age 10 weeks, immunoglobulin G (IgG) autoantibodies have appeared in many of these animals. When NOD strains, partially or completely protected from IDDM by the insertion of transgenes in the class II region, were compared, it was found that the switch to IgG autoantibodies was inhibited and the autoantibodies remained IgM indefinitely. We speculate that the switch to IgG may be a marker of events leading to IDDM in NOD mice and an indication that T-cell help has been generated for responses to beta-cell antigens. Such help not only directs the development of IgG autoantibodies, but more importantly, allows the emergence of potentially pathogenic T-cell clones that are capable of infiltrating the pancreas and mediating beta-cell damage.

Immunogenic properties of synthetic fragments of Sm-D protein in normal and lupus mice.

Antibodies against the Sm antigen are characteristic of systemic lupus erythematosus (SLE). They are found in 20-30% of SLE patients and it has been shown previously that up to 70% of SLE sera react with synthetic fragments 1-20 and 44-67 of the Sm-D polypeptide. To determine whether injections of these peptides might be pathogenic both were administered intraperitoneally into normal mouse strains BALB/c (H-2d), B10/brown (H-2k) and C57BL/6 (H-2b) and an autoimmune strain MRL/lpr (H-2k). IgG antibodies against peptide 1-20 were detected by ELISA in the sera of BALB/c and MRL/lpr mice but not in the sera of B10/brown and C57BL/6 mice. IgG antibodies against peptide 44-67 were found in the sera of BALB/c, B10/brown and MRL/lpr mice but not in the sera of C57BL/6 mice. Neither fragment induced a response against the whole Sm-D antigen as detected by Western blotting. Reactivity to synthetic fragments from other nuclear antigens was however detected in the sera of MRL/lpr mice, especially in those mice injected with Sm-D peptide 44-67 emulsified in Freund's adjuvant. Following immunization with Sm-D peptides, antibodies to ssDNA or dsDNA were not detected in the sera of BALB/c, B10/brown and C57BL/6 mice and in the MRL/lpr mice the naturally occurring production of these antibodies was not enhanced. No difference in IgG deposition in the renal glomeruli of the mice injected with the peptides compared with the control groups was observed. These results suggest that the humoral response to the Sm-D fragment is, at least partially, controlled by the MHC haplotype of the recipient mice, is related to dose and type of immunogen, and is also influenced by the presence of Freund's adjuvant. It is evident that although the sera of many SLE patients recognize either or both the 1-20 and 44-67 peptides, these peptides when injected into MRL/lpr mice are not directly pathogenic.

Symptom severity and diagnoses related to sexual assault history.

The current study examines associations between a history of sexual assault or abuse and severity of symptoms and diagnostic categories in an adult clinical outpatient sample. Twelve of 68 men (18%) and 71 of 120 women (59%) reported a history of sexual trauma. Abuse history was associated with mood and anxiety disorder diagnoses. Women were also more likely to receive these diagnoses; abused women were particularly likely to be diagnosed with an anxiety disorder. Abused subjects showed higher scores on every subscale of the SCL-90-R; there were no interactions between sex and history of abuse. Women scored higher than men on subscales indicating anxiety, phobia, and general distress. The results indicate an association between history of sexual trauma and symptom severity across a broad range of psychopathology, and with mood and anxiety disorders. There is no indication of differential gender effects of sexual assault.

Unique role of thyroxine in T cell recognition of a pathogenic peptide in experimental autoimmune thyroiditis.

We have previously demonstrated the importance of iodination and the requirement of the thyroxine residues in thyroglobulin (Tg) for the stimulation of two clonotypically distinct murine T cell hybridomas reactive against human and mouse Tg. We are now able to show that these T cell hybridomas only recognize an 11-residue peptide containing a thyroxine structure that has iodine at two positions on each ring. This iodination state is critical for recognition by these hybridomas as a peptide containing de-iodinated thyroxine is nonstimulatory. Furthermore we have demonstrated that a peptide lacking the thyroxine residue or containing de-iodinated thyroxine cannot block the recognition of the thyroxine-containing peptide. We suggest that in our system the thyroxine residue is involved in binding to major histocompatibility complex (MHC) class II molecules. We have also been able to show that the thyroxine residue is available for contact by the T cell receptor (TCR) as recognition of the peptide/H-2A(k) complex is blockable by an antibody directed against thyroxine. Using substituted peptides, we have been able partially to define the residues within the peptide that are critical for recognition of the 11-residue peptide by our hybridomas. From our data, we suggest that the thyroxine residue may bind the MHC and TCR, while the residues identified in the peptide backbone as important for the stimulation of the hybridomas may bind only the TCR.

A hospital outbreak of salmonella food poisoning due to inadequate deep-fat frying.

In an outbreak of plasmid-free Salmonella enteritidis phage type 4 (PT4) food poisoning at a hospital for mentally handicapped people in July 1990, 101 residents and 8 staff were affected and a cohort study implicated beef rissoles cooked by deep-fat frying as the vehicle of infection (relative risk 2.92, 95% confidence interval 1.73-4.93, P << 0.001). Replication of the cooking process demonstrated that the rissoles achieved core temperatures of only 48-60 degrees C despite external temperatures of 91-95 degrees C and an oil temperature of 142-154 degrees C. No residual food was available for microbiological testing but plasmid-containing S. enteritidis PT 4 was isolated in shell eggs from the hospital kitchen.

Comparative study of the protective effect afforded by intravenous administration of bovine or ovine insulin to young NOD mice.

Soluble bovine or ovine insulin given intravenously to female NOD mice shortly after weaning had a downregulating effect on several autoimmune parameters associated with insulin-dependent diabetes. The titer of spontaneous anti-insulin antibodies was reduced, insulitis was delayed and less severe, and only 25% of treated mice were diabetic at 30 weeks compared with 70% of untreated mice. An interesting paradox occurred in that bovine insulin, although poorly immunogenic in NOD mice and ineffective as a tolerogen for complete Freund's adjuvant-induced cellular and humoral responses to ovine insulin, was nearly as effective as immunogenic ovine insulin in protecting against diabetes and better than ovine insulin at downregulating spontaneous autoantibodies to insulin. Bovine and ovine insulins differ by only one amino acid on the A-chain loop, but whereas modulation of the induced response to ovine insulin appeared to be sheep-specific, modulation of the induced and spontaneous autoimmunity was achieved almost equally well by bovine or ovine insulin. We suggest therefore that modulation of the induced and spontaneous responses are dependent on different T-cell epitopes and that modulation of spontaneous autoimmunity appears to be governed by an epitope common to both insulins.

Aspartate at position 57 of nonobese diabetic I-Ag7 beta-chain diminishes the spontaneous incidence of insulin-dependent diabetes mellitus.

MHC class II genes have been shown to influence the development of the autoimmune disease insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic (NOD) mouse. In human IDDM it has been suggested that the presence of an aspartate at position 57 of the DQ beta-chain might be important in determining resistance to development of IDDM. The involvement of MHC class II genes in IDDM was investigated through the introduction of MHC encoding transgenes. We show that introduction of a mutated I-Ag7 Ab gene which encodes an aspartate at position 57 reduces the incidence of IDDM but does not prevent insulitis, sialadenitis, or the development of insulin and nuclear autoantibodies.