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.

A thyroxine-containing peptide can induce murine experimental autoimmune thyroiditis.

A synthetic peptide based on a sequence containing thyroxine at position 2553 in thyroglobulin (Tg), and already shown to be recognized by two clonotypically distinct murine Tg autoreactive T cell hybridomas, can trigger primed lymph node cells to transfer thyroiditis to naive recipients. Donor lymph node cells could be prepared from mice immunized either with intact mouse Tg or with this peptide itself. After a second exposure to the priming antigen in vitro, both these populations induced 100% thyroiditis in recipient animals. The importance of the T4 residue in the development of disease was demonstrated by the failure of Tg tryptic peptides depleted of T4 to stimulate pathogenic effectors in vitro, even when the lymph node cells had been taken from mice primed with whole Tg. We conclude that this T4-containing 12mer sequence is a major thyroiditogenic epitope in CBA/J mice although we cannot exclude the possibility that there are other pathogenic epitopes present in the whole Tg molecule.

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.

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.

Tolerance to IDDM induced by CD4 antibodies in nonobese diabetic mice is reversed by cyclophosphamide.

IDDM can be induced in nonobese diabetic (NOD) mice in several ways, including high doses of cyclophosphamide and transfer of diabetic spleen cells to sublethally irradiated recipients. It has previously been established that transferred diabetes can be prevented by treatment with a nondepleting CD4 monoclonal antibody; however, we report herein that cyclophosphamide-induced diabetes also can be prevented using this antibody. The protection induced by CD4 monoclonal antibody to transferred diabetes is maintained for a long period after cessation of antibody treatment. However, cyclophosphamide can abrogate this induced tolerance and we report that this abrogation does not require new T-cells. During the course of the experimental work described, we observed that the thymus had a suppressive effect on the expression of transferred disease. Mice that were depleted of their peripheral T-cells showed a doubling of the time for disease expression if they were euthymic, compared with thymectomized mice.

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 detection and enumeration of cytokine-secreting cells in mice and man and the clinical application of these assays.

An in vitro assay for the detection and enumeration of mouse and human cytokine-secreting cells is described and some ways in which it may be used diagnostically are indicated. The assay is an extension of the ELISA plaque assay or ELISPOT assay and uses pairs of antibodies to capture and then visually develop secreted lymphokines. In this way, it is possible to enumerate the specific cytokine-secreting cells. This assay may provide a valuable tool in the clinical investigation of the mechanisms of disease development and tissue destruction.

Anti-CD4 treatment of NZB mice prevents the development of erythrocyte autoantibodies but hastens the appearance of anaemia.

New Zealand Black (NZB) mice spontaneously develop autoimmune haemolytic anaemia as the result of production of autoantibodies to erythrocytes. We have recently shown that antibodies to CD4 prevent the development of erythrocyte autoantibodies in young mice (Coombs' negative). In spite of this inhibition of erythrocyte autoantibody production, the anti-CD4-treated mice show a precocious and severe anaemia. Balb/c mice treated with the same protocol do not develop anaemia. Our results suggest that erythropoiesis in NZB mice is particularly sensitive to depletion of CD4+ T cells.

Antibody mediated regulation of immune responses. I. Enhancement of specific antibody responses through IgM antibodies.

Injection of monoclonal IgM antibodies to sheep red blood cells (SRBC) 2 h before immunization with a low dose of antigen (Ag) specifically enhances the direct and indirect plaque-forming cell response. This enhancement was specific: the specific antigen had to be present; the plaque-forming cell (PFC) response to TNP-Ficoll- or bromelein-treated mouse red blood cells was not enhanced; the PFC response to SRBC was not enhanced by injections of monoclonal antibody to TNP. The optimum conditions for enhancement were found to be dependent on both the dose and the time of administration of antibody in relation to antigen. The possible mechanisms for this enhanced antibody response are discussed.

The regulation of autoimmunity through CD4+ T cells.

Our experiments imply that it is possible to use monoclonal antibody therapy to reestablish self tolerance to self antigens. This can be achieved by using a short course of an nd anti-CD4 antibody thus avoiding the problem of long term immunosuppression. The mechanism by which such a state of self tolerance is achieved remains to be clarified but possible mechanisms include deletion or anergy of autoreactive T cells or some form of suppression mediated through local cytokine production. As this antibody induced state of tolerance can be reversed in the NOD mouse by cyclophospamide deletion cannot be the method by which autoreactivity is prevented. The mixing experiments which have been described in the thyroiditis experiments strongly suggest that anery is not the mechanism. It therefore remains most likely that tolerance induced following administration of nd anti-CD4 is an active process maintained through the production of an inhibitory cytokine. This ability to reprogram the immune system using monoclonal antibodies makes it not beyond the realms of possibility that individuals suffering from IDDM may become tolerant of their beta cell antigens and thus be able to regenerate their own beta cell mass. If this could indeed occur it might mean that a lifetime of insulin injections and the development of the life threatening complications that may accompany a disease like IDDM may be avoided.

Outbreak of Shigella sonnei dysentery on a long stay psychogeriatric ward.

A ward outbreak of diarrhoea associated with Shigella sonnei on a long stay psychogeriatric ward is described. Nine patients and three staff had positive stool cultures for S. sonnei. The source of infection of the index case was not discovered. Environmental factors at ward level which predispose long stay hospitals to such outbreaks are discussed.

How is the source of food poisoning outbreaks established? The example of three consecutive Salmonella enteritidis PT4 outbreaks linked to eggs.

Three consecutive outbreaks of Salmonella enteritidis PT4 occurred in Wales in 1989 in which epidemiological and microbiological investigation established eggs as the likely source although kitchen inspection and food preparation histories suggested other vehicles of infection. This paper examines the contribution of analytical epidemiology in attributing causation, with particular reference to those limitations which are regarded as inherent in epidemiological evidence. Such evidence, implicating eggs in the three outbreaks, fulfilled 6/7 widely accepted criteria for causation; data to assess the seventh were lacking. Collaboration between different agencies and professionals in investigating outbreaks is very important.

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.

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.

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.