Background
The knowledge about chronic spontaneous urticaria (CSU) phenotypes is based on its clinical characteristics, associated comorbidities, course of the disease, and its response to the ...available effective drugs. Genotype expression and its further correlation with CSU phenotypes are still unknown. We describe the cutaneous transcriptome of patients suffering a severely active CSU refractory to antihistamine treatment.
Methods
Through the bioinformatic analysis of the whole Human Genome with Oligo Microarrays and quantitative real‐time polymerase chain reaction (qPCR), relevant genes expressed in nonlesional (NLS‐CSU) and lesional skin (LS‐CSU) and peripheral blood were identified in 20 patients suffering from severely active CSU and 10 healthy controls (HCs).
Results
From 39 genes differentially expressed in NLS‐CSU when compared with HCs, 31 (79.48%) were confirmed by qPCR corresponding to genes involved in epidermal homeostasis and dermal repair. From the analysis comparing LS‐CSU with NLS‐CSU, a selection of 142 genes was studied with qPCR, and 103 (72.53%) were confirmed. Differentially expressed genes in the phenomenon of wheal development are involved in a variety of biological functions as, epidermal differentiation, intracellular signal function, transcriptional factors cell cycle differentiation, inflammation, or coagulation. Differentially expressed genes that uniformly increase or decrease along the skin worsening until the wheal appearance is shown.
Conclusion
The skin of CSU patients with a severely active disease shows an overall immunological skin involvement showing a peculiar gene profile.
Poly(ADP-ribose)polymerase-1 (PARP-1) is a highly promising novel target in breast cancer. However, the expression of PARP-1 protein in breast cancer and its associations with outcome are yet poorly ...characterized.
Quantitative expression of PARP-1 protein was assayed by a specific immunohistochemical signal intensity scanning assay in a range of normal to malignant breast lesions, including a series of patients (N = 330) with operable breast cancer to correlate with clinicopathological factors and long-term outcome.
PARP-1 was overexpressed in about a third of ductal carcinoma in situ and infiltrating breast carcinomas. PARP-1 protein overexpression was associated to higher tumor grade (P = 0.01), estrogen-negative tumors (P < 0.001) and triple-negative phenotype (P < 0.001). The hazard ratio (HR) for death in patients with PARP-1 overexpressing tumors was 7.24 (95% CI; 3.56–14.75). In a multivariate analysis, PARP-1 overexpression was an independent prognostic factor for both disease-free (HR 10.05; 95% CI 5.42–10.66) and overall survival (HR 1.82; 95% CI 1.32–2.52).
Nuclear PARP-1 is overexpressed during the malignant transformation of the breast, particularly in triple-negative tumors, and independently predicts poor prognosis in operable invasive breast cancer.
Oxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase-like 2 (LOXL2) generates an H3 modification with an unknown physiological function. We find that LOXL2 and H3K4ox are higher in triple-negative ...breast cancer (TNBC) cell lines and patient-derived xenografts (PDXs) than those from other breast cancer subtypes. ChIP-seq revealed that H3K4ox is located primarily in heterochromatin, where it is involved in chromatin compaction. Knocking down LOXL2 reduces H3K4ox levels and causes chromatin decompaction, resulting in a sustained activation of the DNA damage response (DDR) and increased susceptibility to anticancer agents. This critical role that LOXL2 and oxidized H3 play in chromatin compaction and DDR suggests that functionally targeting LOXL2 could be a way to sensitize TNBC cells to conventional therapy.
Introduction: Medical students represent a new generation of medical thought, and if they have a favourable attitude towards organ donation this will greatly encourage its promotion.
Objective: To ...analyse the attitude of medical students in Spanish universities towards the donation of their own organs and to determine the factors affecting this attitude.
Material and Methods: Type of study: A sociological, interdisciplinary, multicentre, and observational study in Spain. Study population: Students studying a degree in medicine enrolled in Spain (n = 34,000). Sample size: A sample of 9598 students (confidence of 99% and precision of ±1%), stratified by geographical area and academic year. Instrument of measurement: A validated questionnaire of attitude towards organ donation and transplantation (PCID-DTO RIOS) was self-administered and completed anonymously.
Results: The questionnaire completion rate was 95.7% (n = 9.275). 80% were in favour of donation, 2% against and 18% were undecided. The following main variables were related to a favourable attitude: being of the female sex (Odds Ratio = 1.739); being in the sixth year of the degree (OR = 2.506); knowing a donor (OR = 1.346); having spoken about the subject with one's family (OR = 2.132) and friends (OR = 1.333); having a family circle that is in favour, more specifically, having a father (OR = 1.841), mother (OR = 2.538) or partner in favour (OR = 2.192); being a blood donor (OR = 2.824); acceptance of the mutilation of the body if it were necessary (OR = 2.958); and being an atheist or an agnostic (OR = 1.766).
Conclusions: Spanish medical students generally have a favourable attitude towards organ donation, although 20% are not in favour.
Detection of posttransplant donor‐specific anti‐HLA antibodies (DSA) constitutes a risk factor for kidney allograft loss. Together with complement activation, NK‐cell antibody‐dependent cell mediated ...cytotoxicity (ADCC) has been proposed to contribute to the microvascular damage associated to humoral rejection. In the present observational exploratory study, we have tried to find a relationship of circulating donor‐specific and nondonor‐specific anti‐HLA antibodies (DSA and HLA non‐DSA) with peripheral blood NK‐cell subsets and clinical features in 393 renal allograft recipients. Multivariate analysis indicated that retransplantation and pretransplant sensitization were associated with detection of posttransplant DSA. Recipient female gender, DR mismatch and acute rejection were significantly associated with posttransplant DSA compared to HLA non‐DSA. In contrast with patients without detectable anti‐HLA antibodies, DSA and HLA non‐DSA patients displayed lower proportions of NK‐cells, associated with increased CD56bright and NKG2A+ subsets, the latter being more marked in DSA cases. These differences appeared unrelated to retransplantation, previous acute rejection or immunosuppressive therapy. Although preliminary and observational in nature, our results suggest that the assessment of the NK‐cell immunophenotype may contribute to define signatures of alloreactive humoral responses in renal allograft recipients.
This single‐center prospective study of kidney transplant recipients shows that patients with detectable anti‐HLA antibodies display lower proportions of NK cells and increased CD56bright and NKG2A+ subsets than patients without antibodies, the latter being more marked in cases with donor‐specific antibodies.
To assess the incidence of severe perioperative anaphylaxis, the mechanisms involved, the value of laboratory/skin tests, and the most effective treatments.
A historical cohort study conducted in a ...tertiary public hospital in Spain. Patients that had undergone anaesthesia during the 20-year period were included. In these patients, 66 cases of severe anaphylaxis were found. In patients with suspicion of severe anaphylaxis, levels of blood histamine at less than 15min and serum tryptase at 2, 6, and 24h following the reaction were determined. Skin and specific IgE tests were performed between 4 and 8 weeks later.
Over the 20-year period, 288 594 anaesthetic procedures were performed. We observed cases of 66 severe anaphylaxis reaction (59% men; age, 60.8±17.3 years. Symptoms observed were cardiovascular (86%), respiratory (73%), and mucocutaneous (56%). Elevated serum tryptase levels were associated with degree of severity at 2 (P<.0001) and 6h (P=.026) and were highest in IgE-mediated reactions (P=.020). All patients required treatment, and 3 events were fatal.
In 84.8% of patients, skin and/or specific IgE tests were positive for antibiotics (35.8%), non-steroidal anti-inflammatory drugs (23.1%), neuromuscular blocking agents (15.4%) and latex (15.4%).
The incidence of severe anaphylaxis in our hospital was 1 in 4.373 anaesthetic procedures, with a death rate of 4.5%. All cases required treatment. Serum tryptase was a good predictor of reaction severity. The most frequent causative agents were antibiotics, non-steroidal anti-inflammatory drugs, neuromuscular blocking agents and latex.
Determinar la incidencia de reacciones perioperatorias graves, los mecanismos implicados, los tratamientos realizados y la utilidad del protocolo diagnóstico propuesto.
Estudio de cohorte histórico en un hospital público terciario en España. Se incluyeron pacientes que recibieron anestesia durante 20 años. En pacientes con sospecha de anafilaxia grave, se determinaron los niveles de histamina en sangre en menos de 15minutos y triptasa sérica a las 2, 6 y 24horas después de la reacción. Se realizaron pruebas cutáneas e IgE específica a las 4-8 semanas.
Durante el período de 20 años, se realizaron 288.594 procedimientos anestésicos. Observamos 66 reacciones de anafilaxia grave (59% hombres; edad: 60,8±17,3 años). Los síntomas fueron cardiovasculares (86%), respiratorios (73%) y mucocutáneos (56%). Los niveles elevados de triptasa sérica se asociaron con un mayor nivel de gravedad a las 2 (P<,0001) y 6 horas (P=.026) y fueron más elevados en las reacciones IgE mediadas (P=,020). Todos los pacientes requirieron tratamiento y la muerte ocurrió en 3 casos. En el 84,8% de los pacientes las pruebas cutáneas y/o IgE específicas fueron positivas a antibióticos (35,8%), antiinflamatorios no esteroideos (23,1%), bloqueantes neuromusculares (15,4%) y látex (15,4%).
La incidencia de anafilaxia grave en nuestro hospital fue 1:4.373 procedimientos anestésicos, con una mortalidad del 4,5%. Todos los casos requirieron tratamiento. La triptasa sérica fue un buen predictor de la gravedad de la reacción. Los agentes etiológicos más frecuentes fueron antibióticos, antiinflamatorios no esteroideos, bloqueantes neuromusculares y látex.
Health professionals are asked to promote health, especially organ transplantation; however, they do not always have specific training.
To analyze information about donation and organ transplantation ...among Spanish medical students.
The population under study is medical students in Spanish universities using the database of the International Donor Collaborative Project, stratified by geographic area and academic year (n = 9275). The instrument used is the attitude questionnaire for organ donation for “PCID-DTO-Ríos” transplantation, validated with an explained variance of 63.203% and α = 0.834. The Student t test was applied together with the χ2 test, complemented by an analysis of the remainders, and Fisher's exact test was applied.
Of the students, 74% indicate that they have received information from university professors about organ transplant. Concerning specific issues with the donation, it is notable that only 66.7% (n = 6190) know and accept the concept of brain death as the death of a person. However, only 22% consider themselves as having good information, and 35.3% indicate that their information is scarce or void. Students indicate having received information about transplant from other extra-university sources, such as television and Internet (80.9%), books and magazines (73.2%), and the press (66.9%). From the information obtained in the sociofamilial field, 60.7% have obtained information from the family and 58.1% from friends. Of this information, 9% has been negative from friends, 7.5% from family, 6% from the Internet and television, and 4% from university professors.
Spanish medical students believe they have little information about organ transplantation and have received negative information.
•Spanish medical students believe they have little information about organ transplantation.•A high percentage of medical students in Spain have received some negative information about donation and organ transplantation.•The sources of information related to the sociofamilial environment are the most influential on the attitude toward donation and organ transplantation among Spanish medical students.•Four percent of medical students indicate having received negative information from university professors about donation and organ transplantation.
Despite sensitization of medical students toward the donation of organs, a non-negligible percentage of students are not in favor of donation.
To analyze the reasons of Spanish medical students who ...do not have a favorable attitude toward the donation of their own organs after death.
The population under study is medical students in Spanish universities, using the database of the International Donor Collaborative Project, stratified by geographic area and academic year. The questionnaire completion was anonymous and self-administered. The study group is medical students with an unfavorable attitude toward organ donation. The assessment instrument used is a validated questionnaire of attitude toward the donation of organs for transplant, “PCID-DTO-Ríos.” The reasons against the donation are valued in the questionnaire through a question.
Of the participants included in the PCID, students who are not in favor of organ donation were selected (n = 1899). Of them, 8.1% (n = 154) are against and 91.1% (n = 1745) are doubtful. The main reasons indicated are the fear of apparent death in 11.4% of respondents, fear of possible mutilation after donation in 11.1%, and religious reasons in 2.6%. Of those, 6.9% indicate other reasons but do not clearly specify the reasons, using words such as “fear” (2.5%) or “doubts about the process” (4.1%); 66.2% (n = 1257) indicated an “assertive refusal” (“I don't want to express my reasons”).
Twenty percent of Spanish medical students are not in favor of donating their organs and are not in favor of showing their reasons.
•Most Spanish medical students who are not in favor of organ donation do not indicate their reasons.•The main reason among Spanish medical students for not being in favor is the fear of apparent death.•Spanish medical students who are not in favor of organ donation are mainly in the first years of their career and without prior awareness of the subject.
Awareness of organ donation among Spanish doctors and medical students is very positive. However, the emerging group of professionals of non-Spanish nationality studying in Spain has not been ...analyzed.
To analyze the differences in the attitudes toward the different types of donation among medical students, according to their nationality.
The population under study is medical students in Spanish universities using the database of the International Collaborative Donor Project, stratified by geographic area and academic year. Groups under study include students of non-Spanish nationality as group 1 (n = 1570) and students of Spanish nationality as Group 2 (n = 7705). Instruments are validated questionnaires of attitude toward donation “PCID-DTO-Ríos,” “PCID-DVR-Ríos,” “PCID-DVH-Ríos,” and “PCID-XenoTx-Ríos.”
The attitude toward the donation of own organs after death is similar in both groups (P = .703). Non-Spaniards are 79.2% in favor compared to 79.6% of Spaniards. Living kidney donation, both unrelated (33.3% vs 29.3% in favor; P = .001) and related (91.2% vs 89, 6% in favor; P = .047), is more favorable among non-Spanish students. There are no differences regarding non-related living liver donation (29.7% vs 29.3% in favor; P = .063), but there are differences in the results for related living liver donation (94.1% vs 88%; P < .001). The attitude toward xenotransplantation of organs is similar (80.8% vs 80.8%; P = .999).
Awareness of the donation of organs among Spanish medical students is similar to non-Spanish students studying in Spain, except the attitude toward living donation.
•The acceptance of different types of organ donation among medical students is high.•The attitude toward living donation is more favorable among non-Spanish medical students studying in Spain.•Medical students in Spain of non-Spanish nationality have the same awareness regarding organ donation as Spaniards, so they do not require special training.
Activation of NF-κB (nuclear factor of kappa light chain gene enhancer in B cells) in response to DNA damage is considered to contribute to repair of genetic lesions, increased cell survival and ...cytokine release. The molecular mechanisms orchestrating this cytoplasmic event involve core components of the nuclear DNA damage response machinery, including ATM-kinase (ataxia telangiectasia mutated kinase) and PARP-1 (poly (ADP-ribose) polymerase 1). The physiological consequences of defective NF-κB activation in this context, however, remain poorly investigated. Here we report on the role of the 'p53-induced protein with a death domain', PIDD, which appears rate limiting in this process, as is PARP-1. Despite impaired NF-κB activation, DNA damage did not increase cell death or reduce clonal survival of various cell types lacking PIDD, such as mouse embryonic fibroblasts or stem and progenitor cells of the hematopoietic system. Furthermore, lymphomagenesis induced by γ-irradiation (IR) was unaffected by deficiency for PIDD or PARP-1, indicating that loss of DNA damage-triggered NF-κB signalling does not affect IR-driven tumorigenesis. However, loss of either gene compromised cytokine release after acute IR injury. Hence, we propose that NF-κB's most notable function after DNA damage in primary cells is related to the release of cytokines, thereby contributing to sterile inflammation.
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