The complex circumstellar environment of supernova 2023ixf.

The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.

The association between the intake of specific dietary components and lifestyle factors and microscopic colitis.

BACKGROUND/OBJECTIVES: The incidence of microscopic colitis (MC) has increased over the previous decades. In addition to smoking and drugs, currently unidentified environmental factors may have a role. The aim of this study was to determine whether specific dietary or other lifestyle factors were associated with the development of MC. SUBJECT/METHODS: The population-based cohort Malmö Diet and Cancer Study of 28 095 individuals was examined. Information about dietary habits was collected by a modified diet history method. Data on anthropometry were measured, and socio-economic and lifestyle factors were collected by questionnaires. Cases of MC were identified in medical registers. Associations were estimated using Cox regression analysis. RESULTS: During a 22-year period, 135 patients were diagnosed with MC. Intakes of protein, carbohydrates, sucrose, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 or omega-6 fatty acids, fibre and zinc were not associated with MC. We could verify the previously reported association between MC and smoking (hazard ratio (HR): 2.29; 95% confidence interval (CI): 1.66-3.84) and the female gender (HR: 3.57; 95% CI: 2.22-5.74). High alcohol consumption was associated with an increased risk for MC (HR: 1.89 for the highest quartile; 95% CI: 0.82-4.33, P for trend=0.032). In a post hoc analysis, alcohol intake including all patients independently of consumption seemed to reduce the smoking-related risk. CONCLUSIONS: Despite a large cohort and a long follow-up period, we could not detect any dietary risk factors for MC. The aetiological mechanisms behind the positive impact of smoking and alcohol on MC risk should be investigated.

Patients with irritable bowel syndrome and dysmotility express antibodies against gonadotropin-releasing hormone in serum.

BACKGROUND: The etiology of irritable bowel syndrome (IBS) and dysmotility is in most cases unknown. Organic, pathognomonic changes have not been described. We have previously demonstrated sporadic expressions of antibodies against gonadotropin-releasing hormone (GnRH) in serum from these patients. The aim of this study was to screen for the presence of GnRH antibodies in healthy subjects and patients with gastrointestinal (GI) diseases. METHODS: Consecutive patients suffering from either IBS, idiopathic dysmotility, GI complaints secondary to diabetes mellitus, celiac disease or inflammatory bowel disease (IBD) were included. Healthy blood donors served as controls. Blood samples were taken for analyzing IgM and IgG antibodies against GnRH using an ELISA method. Medical records were scrutinized with respect to duration of symptoms, co-existing diseases, drug treatments, hereditary factors, and laboratory analyses. KEY RESULTS: Healthy controls expressed low levels of GnRH IgM antibodies in a prevalence of 23%. The prevalence of GnRH IgM antibodies in IBS and dysmotility patients was 42% (P = 0.008), and the levels were higher (P = 0.000). Patients with diabetes mellitus expressed GnRH IgM antibodies in the same prevalence as controls (25%), but in higher levels (P = 0.02). Patients with celiac disease or IBD had the same or lower levels of antibodies. There were no associations between antibodies, other co-existing diseases or laboratory analyses. CONCLUSIONS & INFERENCES: Higher levels of GnRH IgM antibodies were detected in patients with IBS and dysmotility, but not organic GI diseases, compared with healthy controls. These findings suggest that IBS and dysmotility to some extent may be of an autoimmune origin.

Pathogenesis of autoimmune diseases: antibodies against transglutaminase, peptidylarginine deiminase and protein-bound citrulline in primary Sjögren's syndrome, multiple sclerosis and Alzheimer's disease.

Coeliac disease (CD) is becoming a model for understanding the pathogenesis of autoimmune disorders. In CD, antibodies against transglutaminase 2 (TG2) and specific residues of gliadins have been identified. A similar situation is seen in rheumatoid arthritis (RA) with both anti-citrullinated protein antibodies (ACPA) and auto-antibodies against the citrullinating enzyme, peptidylarginine deiminase (PAD). Previously, we have suggested that a complex between an enzyme and its modified substrate constitutes the neoantigen in autoimmune diseases. Our hypothesis is challenged by findings in patients of primary Sjögren's syndrome (pSS) who do not express ACPA, but who have been reported to carry anti-PAD. The aims of our investigation were to reproduce the study claiming the presence of anti-PAD in pSS and screen for ACPA and antibodies against TG2 and PAD in pSS (n = 78), multiple sclerosis (MS) (n = 85) and Alzheimer's disease (AD) (n = 79) using ELISA. With blood donors (n = 100) as controls, no increased occurrence of autoantibodies was found among the patient groups tested. Contrary to what has been published previously, patients with pSS do not express anti-PAD. The hypothesis of a complex between an enzyme and its modified substrate constituting the neoantigen in autoimmune diseases is still valid. The prevalence of anti-PAD, anti-TG2 and ACPA is comparatively restricted. PAD and TG2 do not seem to be involved directly in autoimmune mechanisms in pSS, MS or AD.

Autoimmune markers in lymphoid malignancies.

Chronic immune stimulation such as Helicobacter pylori (hp) infection, Sjögren's syndrome or coeliac disease may initiate non-Hodgkin lymphoma (NHL). The opposite (appearance of autoimmunity) has also been reported. The aim of this study was to describe the pattern of these immune markers in patients with lymphoid malignancies. Sera from 96 patients with NHL (median age 72, range 38-88, F/M 41/55) were analysed with ELISA to determine the frequency of antibodies against guinea pig (gp) and human recombinant (hr) transglutaminase type 2 (Tg2), and hr factor XIII subunit a* (part of the Tg-family), extractable nuclear antigen (ENA), and hp. As hp antibodies decrease in younger age cohorts a sex- and age-matched control group of 768 persons was used. The control population for transglutaminase antibodies consisted of 59 blood donors, (median 42 years, range 19-65) was analysed with a commercial kit. Gp-Tg2-IgG positivity was documented in 72% and hr-Tg2-IgG positivity in 15% (5% positive controls for both; P < 0.001 and ns, respectively). For IgA 3% had gp-Tg2 and 4% hr-Tg2 (5% in controls: ns for both). Anti-FXIII-IgA positivity was found in 22% (5% in controls; P = 0.03). Unspecific anti-ENA-IgG positivity was found in 24% (P < 0.001), while only 2% had specific ENA autoantibodies. Moreover, 36% were positive for anti-hp-IgG, while controls were positive in 54% (P < 0.001). The frequency of unspecific autoantibodies was increased. No differences could be noted in specific autoantibodies (hr-Tg2-IgA). In contrast, fewer than expected were anti-hp-positive. A defective immune response, similar to that in autoimmune diseases, could contribute to the pathogenesis of lymphoid malignancies.

Antibodies against transglutaminases, peptidylarginine deiminase and citrulline in rheumatoid arthritis--new pathways to epitope spreading.

OBJECTIVE: The findings of the involvement of tissue transglutaminase (tTg) in the pathogenesis of coeliac disease (CD) have stimulated progress in the field of auto-immune diseases. Another calcium-dependent cysteine enzyme, peptidylarginine deiminase type 4 (PAD4), seems to be involved in the pathogenesis of rheumatoid arthritis (RA). There are obvious similarities between Tgs and PADs. METHODS: Using enzyme-linked immuno-sorbent assays, we have measured the occurrence of antibodies against guinea pig (gp) and human recombinant (hr) tTg, PAD and citrulline in 59 controls and 184 RA-patients, of whom 71 were treated with methotrexate (mtx). RESULTS: In addition to the expected antibodies against citrulline (62%), sera from the 113 RA-patients without mtx treatment contained significantly increased frequencies of IgG anti-PAD (35%), IgA anti-gp-tTg (34%), IgA anti-hr tTg (20%), IgG anti-gp-tTg (13%) and IgA anti-hr-FXIII (15%) compared to controls. In sera from the mtx-treated RA-patients the expression of antibodies was reduced. In patients not treated with methotrexate there was a statistically significant correlation between, on one hand, IgG anti-PAD and on the other hand, IgG anti-citrulline, IgA anti-gp-tTg, IgA anti-hr-tTg, IgG anti-gp-tTg, IgG anti-hr-tTg, or IgA anti-hr-FXIII. In the mtx-treated group these correlations were less pronounced. CONCLUSION: In addition to the expected antibodies against citrulline, sera from RA-patients contained antibodies against PAD and against Tgs of at least two kinds, indicating that the specificity for anti-tTg in CD is far from complete. Most of the patients displayed more than one antibody, a possible indication of epitope spreading. MTX-treatment reduced the expression of antibodies.

Variation in the CTLA4/CD28 gene region confers an increased risk of coeliac disease.

Susceptibility to coeliac disease involves HLA and non-HLA-linked genes. The CTLA4/CD28 gene region encodes immune regulatory T-cell surface molecules and is a strong candidate as a susceptibility locus. We evaluated CTLA4/CD28 in coeliac disease by genetic linkage and association and combined our findings with published studies through a meta-analysis. 116 multiplex families were genotyped across CTLA4/CD28 using eight markers. The contribution of CTLA4/CD28 to coeliac disease was assessed by non-parametric linkage and association analyses. Seven studies were identified that had evaluated the relationship between CTLA4/CD28 and coeliac disease and a pooled analysis of data undertaken. In our study there was evidence for a relationship between variation in the CTLA4/CD28 region and coeliac disease by linkage and association analyses. However, the findings did not attain formal statistical significance (p = 0.004 and 0.039, respectively). Pooling findings with published results showed significant evidence for linkage (504 families) and association (940 families): p values, 0.0001 and 0.0014 at D2S2214, respectively, and 0.0008 and 0.0006 at D2S116, respectively. These findings suggest that variation in the CD28/CTLA4 gene region is a determinant of coeliac disease susceptibility. Dissecting the sequence variation underlying this relationship will depend on further analyses utilising denser sets of markers.

Positive effects of anabolic steroids, vitamin D and calcium on muscle mass, bone mineral density and clinical function after a hip fracture. A randomised study of 63 women.

A total of 63 women who had an operation for a fracture of the hip was randomly allocated to one year of treatment either with anabolic steroids, vitamin D and calcium (anabolic group) or with calcium only (control group). The thigh muscle volume was measured by quantitative CT. The bone mineral density of the hip, femur and tibia was assessed by quantitative CT and dual-energy x-ray absorptiometry and of the heel by quantitative ultrasound. Quantitative CT showed that the anabolic group did not lose muscle volume during the first 12 months whereas the control group did (p<0.01). There was less bone loss in the proximal tibia in the anabolic group than in the control group. The speed of gait and the Harris hip score were significantly better in the anabolic group after six and 12 months. Anabolic steroids, even in this moderate dose, given in combination with vitamin D and calcium had a beneficial effect on muscle volume, bone mineral density and clinical function in this group of elderly women.

Changes in biochemical markers of bone metabolism and BMD during the first year after a hip fracture.

We measured the levels of biochemical markers of bone formation and bone resorption in hip fracture patients preoperatively and after 6 and 12 months. Bone densitometry was done with quantitative computer tomography (QCT), dual-energy X-ray absorptiometry (DXA) and heel ultrasound. After 6 months, the biochemical markers of bone formation and bone resorption had increased. The levels remained high after 1 year and no change occurred between 6 and 12 months. We found no correlations between biochemical bone markers and bone density/stiffness on admission and change in bone mineral density (BMD) during the first postoperative year, despite the changes in bone markers and bone density. In our opinion, biochemical bone markers can not be used to predict bone loss in the individual patient after a hip fracture.

Haemochromatosis gene mutations in Finns, Swedes and Swedish Saamis.

Frequencies of three different mutant haemochromatosis (HFE) alleles (282Tyr, 63Asp and 65Cys) were studied in three northern European populations, i.e. Finns, Swedes and Swedish Saamis. In Finns and Swedes the allele frequencies were within the range found in other populations from northern and western Europe. The Saamis differed from the Swedes with respect to all mutant alleles. Lower frequencies compared to Swedes were found for the 282Tyr (p = 0.0046) and 63Asp (p = 0.034) alleles, whereas the frequency of the 65Cys allele was higher (p = 0.046) in the Saamis. The total distribution of HFE alleles in Saamis showed a highly significant difference from that in Swedes (chi2 = 16.7, 3 d.f., p = 0.0008). These results further underline the genetic uniqueness of the Saamis.

Gliadin antibodies in adult insulin-dependent diabetes--autoimmune and immunogenetic correlates.

Gliadin antibody (GA) tests used in screening for coeliac disease (CD) frequently yield positive GA results without accompanying CD in cases of diabetes mellitus type 1 (DM-1). To enlighten this phenomenon we screened 848 DM-1 patients for IgA- and IgG-GA. Subsequently, 16 out of 19 high titre GA patients (6 with CD) were compared with 37 low titre DM-1 patients matched for sex, age and disease duration, for autoimmune and immunogenetic markers. Chronic thyroiditis and thyroid peroxidase (TPO) antibody positivity were more frequent in the GA-positive than in the GA-negative sub-group (38 vs. 2.7%, p = 0.003, and 69 vs. 27%, p < 0.00, respectively). The tissue transglutaminase (tTg) IgA titres correlated with CD but not with GA. tTg IgG titres were lower in GA-positive individuals (p = 0.0012). GA-positivity correlated with a higher titre of factor XIII IgA antibodies (p < 0.001). GA-positive DM-I patients were characterised by a distinct immunogenetic profile; the risk of HLA DQB1*02 was lower among GA-positive patients than among GA-negatives (OR 0.4, preventive fraction 0.43). All CD patients were HLA DRB1*03-DQB1* 02-positive, but none of the five patients with normal biopsies. GA-positive patients instead had HLA DRB1*13 in 37.5% as compared to 8.6% in GA-negative (OR 6.4, etiologic fraction 0.32). Thus, the occurrence of positive GA in DM-1 is correlated to TPO antibody positivity, thyroiditis and factor XIII IgA antibodies, but inversely correlated to tTg IgG, and seems to be associated with another HLA haplotype than that previously found to be associated with CD.

Nesting mallards (Anas platyrhynchos) forecast brood-stage food limitation when selecting habitat: experimental evidence.

By combining and reanalysing data from two independent field experiments we explore whether food limitation at the brood stage affects habitat selection in nesting mallards (Anas platyrhynchos). In an introduction experiment we found that, independent of treatment, some study lakes remained empty of wild mallard pairs ("empty lakes"), whereas on other lakes introduced birds attracted wild mallards ("attractive lakes"). In the other experiment we used mallard ducklings to address brood-stage food limitation by studying mass change of ducklings. We found that ducklings foraging on lakes that did not attract wild mallard pairs in the introduction experiment gained much less mass than those foraging on attractive lakes. In most cases ducklings even lost mass in the empty-lake foraging trials, providing strong evidence for food limitation. Therefore, lakes that remained empty of wild mallard pairs in the introduction experiment proved to be inferior brood habitats, particularly in terms of food. Our results give insight into the mechanisms underlying the general habitat selection hypotheses, specifically the ideal preemptive and conspecific attraction rules. The results further support our earlier conclusion that mallards do not use the ideal preemptive rule when selecting nesting lakes. However, conspecific attraction may not be generally applicable either, because, independent of the presence of introduced conspecifics, wild mallards somehow anticipated the low quality of the empty lakes as brood-rearing habitats and made their habitat-selection decision accordingly.

Contribution of the MHC region to the familial risk of coeliac disease.

Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.

Tryptophan hydroxylase autoantibodies and intestinal disease in autoimmune polyendocrine syndrome type 1.

Tryptophan hydroxylase antibodies, associated with gastrointestinal disease in autoimmune polyendocrine syndrome type 1, are specific for this disease and not present in patients with other bowel disorders or healthy controls.

Prevalence of IgA-antiendomysium and IgA-antigliadin autoantibodies at diagnosis of insulin-dependent diabetes mellitus in Swedish children and adolescents.

OBJECTIVE: This study was conducted to investigate the prevalence of celiac disease (CD) in children and adolescents at diagnosis of insulin-dependent diabetes mellitus (IDDM) before insulin treatment was started. MATERIAL AND METHODS: At diagnosis of IDDM, and before treatment was started, 115 children and adolescents were screened for IgA- antiendomysium (EMA) and IgA-antigliadin antibodies (AGA). Those found to be EMA-positive and/or AGA-positive were investigated further with intestinal biopsy. RESULTS: Of the 115 patients, 2 had known CD at diagnosis of IDDM; of the remainder of patients, 6% (7/113) were found to be EMA-positive and 9% (10/113) were found to have AGA levels above normal. Of the 6 patients who underwent biopsy, 5 manifested villous atrophy. In addition, 2 patients with high EMA and AGA antibody titers refused biopsy, and 4 patients with low EMA and/or AGA titers were found to have normal titers at control before biopsy decision. CONCLUSION: Because the prevalence of CD at diagnosis of IDDM would seem to be 6% to 8%, screening for CD seems to be justified among patients with newly diagnosed IDDM.

Evidence of gastrointestinal immune reactivity in patients with sarcoidosis.

OBJECTIVES: The aim of the present study was to explore the frequency of clinical and serological manifestations of gastrointestinal immune reactivity in a large group of Swedish patients with sarcoidosis. DESIGN: In patients with documented sarcoidosis, the presence of pernicious anaemia and coeliac disease was examined. Antibodies to H+/K+ ATPase, gliadin (AGA-IgA/IgG) and endomysium (IgA-EMA) were analysed. In H+/K+ ATPase antibody-positive patients, serum gastrin levels were measured and, when elevated, gastrointestinal biopsy was offered (biopsy performed in 6/9 patients): biopsy was also offered to those with positive EMA or AGA of either class (biopsy performed in 8/12 patients). Subjects from national and local studies were used as controls. SETTING: The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden. SUBJECTS: Of all patients (n = 89) with documented sarcoidosis attending the Department of Pulmonary Medicine between January 1980 and December 1991, 78 [34 females and 44 males; median age at the time of the study, 48 (range 22-81) years; median observation time since the diagnosis of sarcoidosis, 120 (range 1-468) months] were examined. RESULTS: Twenty-nine patients (37.2%) had signs of gastrointestinal immune reactivity. H+/K+ ATPase antibodies were detected in 19 patients (24.4 vs. 4% in controls, P = 0.00015). Serum gastrin levels (median 45, range 22-720 pmol L(-1)) in those patients correlated with antibody titre (r2 = 0.882). Gliadin antibodies were detected in 12 patients (15.4 vs. 8.1% in controls, P = 0.042), of whom 11 (14.1 vs. 4.5% in controls, P = 0.00114) had AGA-IgA alone. One patient had pernicious anaemia and another coeliac disease (EMA-positive). CONCLUSION: We have demonstrated a high frequency of gastric autoimmunity and gluten-associated immune reactivity in patients with sarcoidosis, occurring in almost 40% of the cases, the former being the most frequent gastrointestinal immune manifestation. Despite a high frequency of humoral autoimmunity, the frequencies of clinical disease, pernicious anaemia and coeliac disease were not increased as compared with the control population.

Regional differences in coeliac disease prevalence in Scandinavia?

BACKGROUND: According to investigations from the central region of Sweden (Linköping), Norway, and Finland based on antibody screening, the prevalence of coeliac disease (CD) is around 1:300 (0.33%). In Denmark surveys in paediatric departments have shown a prevalence of only 1:10,000. The aim of the present study was to study the prevalence of CD in southern Sweden. METHODS: From October 1996 to February 1997, 1970 healthy blood donors were screened for CD in a serial procedure: first IgA and IgG gliadin antibodies (GA) and then endomysial antibodies in those positive for GA. RESULTS: One patient had previously known CD. Two patients had gastrointestinal symptoms and an increased number of intraepithelial lymphocytes, with improvement on a gluten-free diet. Three of 185 GA-positive blood donors had endomysial antibodies and biopsy-verified CD. Thus, 4 of 1970 blood donors had classic CD, resulting in a prevalence of 1:492 (0.20%)--that is, rather similar to that found in Linköping, Sweden, and in Finland and Norway. If the two persons with gluten-sensitive diarrhoea were also included, the prevalence was 6:1970 = 1:328, or 0.30%. CONCLUSIONS: The prevalence of classic CD (1:492) in southern Sweden is comparable to that found in the rest of Scandinavia, except for Denmark.