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Introduction There are more than ten thousand homeless people in Hungary. Earlier studies confirmed the connection between mental health issues and homelessness. Furthermore, homeless care places a significant burden on the healthcare system, with psychiatric departments being no exception. Objectives to compare demographic and treatment characteristis of homeless and not homeless inpatients in the psychiatric department of Jahn Ferenc South Pest Hospital (JFSPH), and thus providing a different perspective compared to previous studies, shedding light on the relationships from a different angle. Methods In our retrospective study, we analyzed all inpatients’ data treated in the psychiatric department of JFSPH over a 4-month period (03/2023-07/2023). Patients were divided into two groups: those with housing and those who were homeless. We compared the two groups based on the following variables: gender, age, length of inpatient treatment, diagnosis, psychiatric history, employment status; smoking, alcohol and drug use; valid health insurance, invalidity pension and guardianship status; and long-acting injectable antipsychotic treatment. Results The percentage of homeless individuals treated in the psychiatric department of JFSPH was 18%. There was a significant difference in the length of inpatient stay between the two groups, homeless patients spent more than 100% longer time under inpatient treatment. Regarding psychiatric history, there was no significant difference between the two patient groups. When examining the employment status of the sample, we found significantly more unemployed patients im the homeless group. Comparing to the control group, there were significantly more alcohol consumers, smokers, and substance users among the homeless. Long-acting antipsychotic injections were administered significantly more frequently to homeless patients. A significantly higher percentage of homeless individuals were declared invalidated, and a significantly higher proportion of them were placed under guardianship compared to the group with housing. Homeless individuals were significantly more likely to have no social insurance compared to the control group. Conclusions In summary, we can conclude that significant difference have been found between the homeless and not homeless groups in most of the examined variables. These results implicates that the inpatient care of homeless patients poses significant bourden on the inpatient system. Early prevention and effective rehabilitation of substance use disorders could decrease this burden. Establishing a proper social safety network and enhancing community psychiatric care could potentially also relieve the burden of inpatient care system. Disclosure of Interest None Declared

Kyrle's disease is also known as hyperkeratosis follicularis et parafollicularis in cutem penetrans and is classified as a subtype of acquired perforating dermatosis. Kyrle's disease is extremely rare in children and is often associated with underlying chronic conditions, more typically kidney disease and diabetes mellitus, but also congestive heart failure, hyperlipidemia, infectious diseases such as HIV and liver failure. To date, only one clinical work has described an association between cquired perforating dermatosis and sclerosing cholangitis in an adult patient. The current report describes a case of Kyrle's disease associated with sclerosing cholangitis in a 4-year-old girl. [ABSTRACT FROM AUTHOR]

Despite the targeted- and immunotherapies used in the past decade, survival rate among patients with metastatic melanoma remains low, therefore, melanoma is responsible for the majority of skin cancer-related deaths. The ongoing investigation of natural antitumor agents, the nonpsychoactive cannabinoid, cannabigerol (CBG) found in Cannabis sativa is emerging as a promising candidate. CBG offers a potential therapeutic role in the treatment of melanoma demonstrating cell growth inhibition in some tumors. Its low water solubility and bioavailability hinder the potential effectiveness. To address these challenges, a modified CBG, namely LE-127/2 was synthesized by Mannich-type reaction. The aim was to investigate the effect of this novel compound on cell proliferation as well as the mechanism of cell death with a particular focus on autophagy and apoptosis. Human cutan melanoma cell lines, WM35, A2058 and WM3000 were utilized for the present study. Cell proliferation of the cells after the treatment with LE-127/2, parent CBG or vemurafenib was assessed by Cell Titer Blue Assay. Cells were treated with a 1.25-80 µM of the above-mentioned compounds, and it was found that at 20 μM of all drugs showed a comparable effective inhibition of cell proliferation, however, vemurafenib and CBG proved to be more effective than LE-127/2. In addition, clonogenic cell survival assays were performed to examine the inhibitory effect of LE-127/2 on the colony formation ability of melanoma cell lines. Cells treated with 20 µM of LE-127/2 for 14 days showed about a 50% suppression of clonogenic cell survival. LE-127/2 exerted the most intensive inhibition on A2058 cell colonies. Furthermore, notably, LDH cytotoxicity assay performed on HaCaT cell line, proved LE-127/2 to be cytotoxic only at higher concentration, such as 80 μM, while the parent CBG was cytotoxic at concentration as low as 5 μM, suggesting that the new CBG derivative as a drug candidate may be applied in human pharmacotherapy without causing a substantial damage in intact epidermal cells. Analysis of protein expression revealed the impact of LE-127/2 on the expression of basic proteins (LC-3, Beclin-1 and p62) involved in the process of autophagy in the three different melanoma cell lines studied. Elevated expression of these proteins was detected as a result of LE-127/2 (20 µM) treatment. LE-127/2 also induced the expression of some proteins involved in apoptosis, and it is particularly noteworthy the increased level of cleaved PARP. Based on the results obtained, it can be concluded that LE-127/2 induced autophagy could lead to the inhibition of cell proliferation and death in melanoma cells., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Limited research has examined whether accumulation of discrimination over time is associated with worse mental health and whether such experiences are related to socioeconomic status (SES)., Methods: A sample of UK adults with self-reported discrimination experiences (n = 3863) was taken from three waves of the UK Household Longitudinal Study (2015-2020). Multinomial logistic regression assessed associations between SES (income, education, occupation) and cumulative discrimination (number of timepoints discrimination was reported). Logistic regression models assessed prospective associations between cumulative discrimination and probable mental health problems (GHQ-12; 4+ threshold)., Results: Those with lower income were more likely to report discrimination at one timepoint (vs. none). No SES measures were associated with experiencing discrimination at multiple timepoints. Participants who reported one timepoint of discrimination (vs. no experiences) were significantly more likely to report probable mental health problems (OR = 1.47, p < .001, 95% CI 1.20-1.80). Moreover, compared to those experiencing one timepoint, participants reporting multiple timepoints of discrimination were significantly more likely to report probable mental health problems (OR = 1.46, p = .002, 95% CI 1.15-1.86), indicating a cumulative association between discrimination and mental health. There was limited evidence that SES moderated this cumulative association., Limitations: Mental health measures were based on self-report questionnaires and not a clinical diagnosis., Conclusions: Amongst a sample of UK adults, perceiving discrimination at multiple timepoints increased the likelihood of experiencing probable mental health problems. There was limited evidence that this cumulative association differed by SES. National measures designed to reduce discrimination may benefit mental health., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups., Aims: To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire., Method: Data was collected by the East Lancashire Early Intervention Service, identifying all cases of first episode psychosis (FEP) within their catchment area between 2012 and 2020. Multilevel Poisson regression analyses were used to compare incidence rates between Pakistani and White majority groups, while controlling for age, gender and area-level deprivation. The ethnic density effect was also examined by comparing incidence rates across high and low density areas., Results: A total of 455 cases of FEP (364 White, 91 Pakistani) were identified. The Pakistani group had a higher incidence of FEP compared to the White majority population. A clear effect of ethnic density on rates of FEP was shown, with those in low density areas having higher incidence rates compared to the White majority, whereas incidence rates in high density areas did not significantly differ. Within the Pakistani group, a dose-response effect was also observed, with risk of FEP increasing incrementally as ethnic density decreased., Conclusions: Higher ethnic density related to lower risk of FEP within the Pakistani population in East Lancashire, highlighting the impact of local social context on psychosis incidence.

Hydrogen sulfide (H 2 S), a gasotransmitter, plays a crucial role in vasorelaxation, anti-inflammatory processes and mitigating myocardial ischemia/reperfusion-induced injury by regulating various signaling processes. We designed a water soluble H 2 S-releasing ascorbic acid derivative, BM-164, to combine the beneficial cardiovascular and anti-inflammatory effects of H 2 S with the excellent water solubility and antioxidant properties of ascorbic acid. DPPH antioxidant assay revealed that the antioxidant activity of BM-164 in the presence of a myocardial tissue homogenate (extract) increased continuously over the 120 min test interval due to the continuous release of H 2 S from BM-164. The cytotoxicity of BM-164 was tested by MTT assay on H9c2 cells, which resulted in no cytotoxic effect at concentrations of 10 to 30 μM. The possible beneficial effects of BM-164 (30 µM) was examined in isolated 'Langendorff' rat hearts. The incidence of ventricular fibrillation (VF) was significantly reduced from its control value of 79 % to 31 % in the BM-164 treated group, and the infarct size was also diminished from the control value of 28 % to 14 % in the BM-164 treated group. However, coronary flow (CF) and heart rate (HR) values in the BM-164 treated group did not show significantly different levels in comparison with the drug-free control, although a non-significant recovery in both CF and HR was observed at each time point. We attempted to reveal the mechanism of action of BM-164, focusing on the processes of autophagy and apoptosis. The expression of key autophagic and apoptotic markers in isolated rat hearts were detected by Western blot analysis. All the examined autophagy-related proteins showed increased expression levels in the BM-164 treated group in comparison to the drug-free control and/or ascorbic acid treated groups, while the changes in the expression of apoptotic markers were not obvious. In conclusion, the designed water soluble H 2 S releasing ascorbic acid derivative, BM-164, showed better cardiac protection against ischemia/reperfusion-induced injury compared to the untreated and ascorbic acid treated hearts, respectively., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hydrogen sulfide (H 2 S) plays an important role in cardiac protection by regulating various redox signalings associated with myocardial ischemia/reperfusion (I/R) induced injury. The goal of the present investigations is the synthesis of a newly designed H 2 S-releasing ibuprofen derivative, BM-88, and its pharmacological characterization regarding the cardioprotective effects in isolated rat hearts. Cytotoxicity of BM-88 was also estimated in H9c2 cells. H 2 S-release was measured by an H 2 S sensor from the coronary perfusate. Increasing concentrations of BM-88 (1.0 to 20.0 µM) were tested in vitro studies. Preadministration of 10 µM BM-88 significantly reduced the incidence of reperfusion-induced ventricular fibrillation (VF) from its drug-free control value of 92% to 12%. However, no clear dose dependent reduction in the incidence of reperfusion-induced VF was observed while different concentrations of BM-88 were used. It was also found that 10 µM BM-88 provided a substantial protection and significantly reduced the infarct size in the ischemic/reperfused myocardium. However, this cardiac protection was not reflected in any significant changes in coronary flow and heart rates. The results support the fact that H 2 S release plays an important role mitigating reperfusion-induced cardiac damage., Competing Interests: Declaration of Competing Interest All the authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: There have been increasing calls for schizophrenia to be renamed to reduce negative associations with the diagnosis. 'Psychosis' is one proposed alternative, yet some research suggests this has greater negative connotations. This study compared the use of both terms within UK newspapers longitudinally to assess which is more negatively portrayed in the media., Study Design: Using LexisLibrary News, six UK newspaper archives were searched for the terms 'schizophrenia' and 'psychosis' in articles published between 2000 and 2019; the included article total was n = 9802. Articles were analysed using Linguistic Inquiry and Word Count software., Study Results: A two-level multilevel model was created of newspaper articles nested within newspapers. Adding predictors revealed that diagnostic term was a significant predictor of the emotional tone of articles (β = -2.30, SE = 0.51, p < .001, 95 % CI -3.30 to -1.30), with 'psychosis' having a more negative tone than 'schizophrenia.' Tabloids were shown to have a significantly more negative tone than broadsheets (β = -9.32, SE = 1.04, p < .001, 95 % CI -11.36 to -7.28), and emotional tone of writing had become more negative over time (β = -0.26, SE = 0.04, p < .001, 95 % CI -0.34 to -0.18)., Conclusions: These findings suggest 'psychosis' is associated with greater negativity than 'schizophrenia' within UK newspapers, and may be a poor substitute term to reduce stigma. As article tone worsened for both diagnoses over time, increased stigma reduction campaigns are required to target negativity within the media., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The synthesis of 3,4-ethylene-bridged 1,1,2,5-tetrasubstituted biguanides is reported, which are accessible by three alternative routes. Exemplary molecular structures of the ligand and an observed side product have been elucidated by X-ray diffraction analysis. Mono- and dinuclear complexes of the biguanide in both its neutral and monoanionic forms were obtained, including examples of aluminum, copper, magnesium, potassium, tin, and zinc, indicating a versatile coordination behavior, as evidenced by means of single-crystal X-ray diffraction analysis.

Background: The approvals of immune checkpoint inhibitors for several cancer types and the rapidly growing recognition that T cell-based immunotherapy significantly improves outcomes for cancer patients led to a re-emergence of cancer vaccines, including dendritic cell (DC)-based immunotherapy. Blood and tissue biomarkers to identify responders and long-term survivors and to optimize cost and cost-effectiveness of treatment are greatly needed. We wanted to investigate whether blood eosinophilia is a predictive biomarker for patients with solid tumors receiving vaccinations with DCs loaded with autologous tumor-RNA., Methods: In total, 67 patients with metastatic solid tumors, who we treated with autologous monocyte-derived DCs transfected with total tumor mRNA, were serially analyzed for eosinophil counts and survival over the course of up to 14 years. Eosinophilic counts were performed on peripheral blood smears., Results: Up to 87% of the patients treated with DC-based immunotherapy experienced at least once an eosinophilia of ≥ 5% after initiation of therapy; 61 % reached levels of ≥ 10% eosinophils, and 13% of patients showed eosinophil counts of 20% or above. While prevaccination eosinophil levels were not associated with survival, patients with blood eosinophilia at any point after initiation of DC-based immunotherapy showed a trend towards longer survival. There was a statistically significant difference for the patients with eosinophil counts of 20% or more (p = 0.03). In those patients, survival was prolonged to a median of 58 months (range 2-111 months), compared to a median of 20 months (range 0-119 months) in patients with lower eosinophil counts. In 12% of the patients, an immediate increase in eosinophil count of at least 10 percentage points could be detected after the first vaccine, which also appeared to correlate with survival (65 vs. 24 months; p = 0.06)., Conclusion: Blood eosinophilia appears to be an early, on-therapy biomarker in patients with solid tumors undergoing vaccination with RNA-transfected DC, specifically autologous tumor mRNA-transfected DC vaccines, and it correlates with long-term patient outcome. Eosinophilia should be systematically investigated in future trials., Competing Interests: A.M. received travel grants or speaker fees from Abbvie, Almirall, Bristol-Myers Squibb, Pfizer, and Roche. G.S. and B.S.T. hold various patents related to DC vaccination. The companies had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The other authors declare no potential conflicts of interest.

Introduction: The EDITION development program confirmed that insulin glargine 300 U/mL (Gla-300) provides comparable glycemic control to insulin glargine 100 U/mL (Gla-100) but with lower hypoglycemia risk. Our study aimed to evaluate the effectiveness of Gla-300 in everyday practice., Methods: This one-arm, non-interventional study included patients with type 2 diabetes who were switched to Gla-300-based basal-bolus therapy (BBT) and followed for 6 months. Indications for switching included inadequate glycemic control and/or hypoglycemic events with the previous regimen., Results: Overall 229 patients were included, with mean age of 60.9 years. All glycemic variables improved between baseline and 6 months significantly (mean ± standard deviation [SD] hemoglobin A1c [HbA1c] from 8.9 ± 1.5% to 7.5 ± 1.1%, fasting blood glucose from 9.5 ± 3.1 mmol/L to 7.0 ± 2.1 mmol/L, postprandial blood glucose from 12.0 ± 3.8 mmol/L to 8.9 ± 2.5 mmol/L). Gla-300 doses were increased and mealtime insulin doses were unchanged. Rates of both non-severe and severe hypoglycemic events decreased significantly compared to pre-study and 6-month follow-up periods. Patients switched because of elevated HbA1c had higher baseline HbA1c and greater decrease in HbA1c paralleled with increase in insulin doses compared to those switched because of hypoglycemia., Conclusions: In day-to-day practice, switching from human insulin to Gla-300-based BBT resulted in significant improvement in glycemic control and decrease in hypoglycemia risk.

Nowadays, the assessment of the mechanical competence of tissue engineering scaffolds based on computer simulations is a well-accepted technology. Typically, such simulations are performed by means of the Finite Element (FE) method, with the underlying structural model being created based on micro-computed tomography (microCT). Here, this analysis modality is applied to a new, ternary composite, consisting of PHBV, i.e. poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PLGA, i.e. poly(lactic-co-glycolide), as well as of TCP, i.e. tricalcium phosphate hydrate. The studied scaffold structure is made up by fibers of this new composite material, manufactured by means of the rapid prototyping method. The data collected from microCT is utilized for adequately defining the mechanical properties of the FE model. In particular, the three-dimensional field of grey values is interpreted in terms of the underlying field of attenuation coefficients, taking into account the photon energy employed in microCT imaging, eventually allowing for calculation of the three-dimensionally distributed, voxel-specific composition of the studied material. For the sake of keeping the FE simulations as efficient as possible, groups of voxels are combined into one finite element; the grey value of the latter is obtained by volume averaging. Employing a two-step micromechanical homogenization scheme, the experimentally accessible stiffness of the three constituents (PHBV, PLGA, and TCP) is then, finite element by finite element, upscaled to the composition-dependent stiffness of the composite material. The plausibility and adequacy of the FE model is demonstrated by simulating the effects of uniaxial compression on the scaffold structure, in terms of resulting stress and strain fields, highlighting the importance of the fiber junctions (as they are the mechanically most stressed regions), and that neglecting the material heterogeneity would lead to a potentially significant underestimation of stresses and strains. Finally, a comparison is made of the employed analysis modality of microCT data with a previously pursued, simplified analysis strategy, highlighting the conceptual superiority of the former, and pointing out the application limits of the latter., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Trichothiodystrophy, also called sulphur-deficient brittle hair syndrome, is a rare autosomal recessive genetic disorder of DNA repair and transcription. Trichothiodysthrophy is characterised by dry, thin, easily broken hair, showing alternating light and dark pattern called 'tiger tail' banding under polarizing light microscopy. According to our knowledge, our report is the first one on this rare disorder from Hungary: a case of a 9-year-old boy showing clinical features typical of trichotiodystrophy. Sequence analysis of the ERCC2 gene identified two recurrent trichothidodystrophy missense heterozygous mutations - c.934G/A p.Asp312Asn (CM015299) and c.2251A/C p.Lys751Gln (CM004814) - suggesting compound heterozygous state of the patient and confirming the clinically suspected diagnosis of trichothiodystrophy.

In coeliac disease (CD), anti-tissue transglutaminase 2 immunoglobulin (Ig)A antibodies (anti-TG2) are produced and deposited in the intestine. PreventCD (www.preventcd.com) is a European multi-centre study, which investigates the influence of infant nutrition and that of genetic, immunological and other environmental factors on the risk of developing CD. The aim of the current study was to evaluate the appearance of intestinal anti-TG2 deposits in very early intestinal biopsies from at-risk infants and their predictive value for villous atrophy. Sixty-five small bowel biopsies, performed in 62 children, were investigated for the presence of intestinal anti-TG2 extracellular IgA deposits by using double immunofluorescence. The biopsies were performed in the presence of elevated serum levels of CD-associated antibodies and/or symptoms suggesting disease. Deposits of anti-TG2 IgA were present in 53 of 53 CD patients and three of three potential CD patients. In potential CD patients, mucosal deposits showed a patchy distribution characterized by some areas completely negative, whereas active CD patients had uniformly present and evident mucosal deposits. Only one of six patients without CD (negative for serum anti-TG2 and with normal mucosa) had intestinal deposits with a patchy distribution and a weak staining. Two of the 53 CD patients received a definitive diagnosis of CD after a second or third biopsy; mucosal deposits of anti-TG2 IgA were evaluated in all samples. Before developing villous atrophy, both patients had anti-TG2 deposits in normal mucosal architecture, antibodies in one patient being absent in serum. We demonstrated that in CD the intestinal deposits of anti-TG2 are a constant presence and appear very early in the natural history of disease., (© 2017 British Society for Immunology.)

This study aimed to examine how stigma impacts on symptomatic and subjective recovery from psychosis, both concurrently and longitudinally. We also aimed to investigate whether self-esteem and hopelessness mediated the observed associations between stigma and outcomes. 80 service-users with psychosis completed symptom (Positive and Negative Syndrome Scale) and subjective recovery measures (Process of Recovery Questionnaire) at baseline and 6-months later, and also completed the King Stigma Scale, the Self-Esteem Rating Scale and the Beck Hopelessness Scale at baseline. In cross sectional regression and multiple mediation analyses of the baseline data, we found that stigma predicted both symptomatic and subjective recovery, and the effects of stigma on these outcomes were mediated by hopelessness and self-esteem. When the follow-up data were examined, stigma at baseline continued to predict recovery judgements and symptoms. However, self-esteem only mediated the effect of stigma on PANSS passive social withdrawal. Self-esteem and hopelessness should be considered in interventions to reduce the effects of stigma. Interventions that address the current and long-term effects of stigma may positively affect outcome for people being treated for psychosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

A mutation in the hydin gene has been recently described as one possible mechanism leading to lethal congenital hydrocephalus in mice, and a similar defect is proposed to be involved in an autosomal recessive form of hydrocephalus in human. Here, we report for the first time on the cancer association and immunogenicity of two HYDIN variants in humans. One is a previously described sequence derived from the chromosome 1 gene copy, that is, KIAA1864. The second is encoded by a novel alternative transcript originating from the chromosome 16, which we identified by immunoscreening of a testis-derived cDNA expression library with sera of patients with colorectal cancer, and called MO-TES391. Both variants are targeted by immunoglobulin G antibodies in a significant subset of cancer patients but only rarely in healthy donors. Moreover, we identify HLA-A*0201-restricted sequences derived from MO-TES391 and KIAA1864, which are specifically recognized by human cytotoxic CD8(+) T cells. Taken together, these results suggest frequent and coordinated adaptive immune responses against HYDIN variants in patients with cancer and propose HYDIN as a novel cancer-associated antigen., (©2013 AACR.)

IMA901 is the first therapeutic vaccine for renal cell cancer (RCC) consisting of multiple tumor-associated peptides (TUMAPs) confirmed to be naturally presented in human cancer tissue. We treated a total of 96 human leukocyte antigen A (HLA-A)*02(+) subjects with advanced RCC with IMA901 in two consecutive studies. In the phase 1 study, the T cell responses of the patients to multiple TUMAPs were associated with better disease control and lower numbers of prevaccine forkhead box P3 (FOXP3)(+) regulatory T (T(reg)) cells. The randomized phase 2 trial showed that a single dose of cyclophosphamide reduced the number of T(reg) cells and confirmed that immune responses to multiple TUMAPs were associated with longer overall survival. Furthermore, among six predefined populations of myeloid-derived suppressor cells, two were prognostic for overall survival, and among over 300 serum biomarkers, we identified apolipoprotein A-I (APOA1) and chemokine (C-C motif) ligand 17 (CCL17) as being predictive for both immune response to IMA901 and overall survival. A randomized phase 3 study to determine the clinical benefit of treatment with IMA901 is ongoing.

Peptides presented at the cell surface reflect the protein content of the cell; those on HLA class I molecules comprise the critical peptidome elements interacting with CD8 T lymphocytes. We hypothesize that peptidomes from ex vivo tumour samples encompass immunogenic tumour antigens. Here, we uncover >6000 HLA-bound peptides from HLA-A*02(+) glioblastoma, of which over 3000 were restricted by HLA-A*02. We prioritized in-depth investigation of 10 glioblastoma-associated antigens based on high expression in tumours, very low or absent expression in healthy tissues, implication in gliomagenesis and immunogenicity. Patients with glioblastoma showed no T cell tolerance to these peptides. Moreover, we demonstrated specific lysis of tumour cells by patients' CD8(+) T cells in vitro. In vivo, glioblastoma-specific CD8(+) T cells were present at the tumour site. Overall, our data show the physiological relevance of the peptidome approach and provide a critical advance for designing a rational glioblastoma immunotherapy. The peptides identified in our study are currently being tested as a multipeptide vaccine (IMA950) in patients with glioblastoma.

Three children (two boys and one girl) from the same family presented with photosensitivity, hyperpigmentation, hypertrichosis, mild skin fragility, blistering and scarring in childhood. On examination, the cutaneous lesions were found to have improved since their previous examinations. Laboratory tests showed raised plasma and urine carboxyporphyrins and decreased uroporphyrinogen decarboxylase enzyme activity in red blood cells. Triggering factors for porphyria were not detected except for a hepatitis C virus infection in the younger boy. The girl's clinical symptoms recurred in late adolescence, after iron and oestrogen treatments. Mutation analysis of the UROD gene detected two missense mutations, 19 A-->G M1V (novel) and 703C-->T P235S (previously reported), in an uncommon compound heterozygous manner in the three siblings.