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Background: Bacterial lysates are known to modulate the immune response against respiratory infections. However, the effects of the commercial bacterial lysate Pulmonarom® on dendritic cells—particularly human monocyte-derived dendritic cells (moDCs)—have not been studied. Additionally, limited data are available on the expression of Toll-like receptors (TLRs) and cytokines following stimulation with bacterial lysates. Methods: Human monocytes were isolated from buffy coats and differentiated into moDCs. Pulmonarom® was lyophilized, quantified, and used to stimulate moDCs. Ultrastructural changes were evaluated using transmission electron microscopy. The expression of TLRs and selected cytokines was analyzed by flow cytometry. Results: Pulmonarom® stimulation induced morphological changes in moDCs, including an increased number of dendrites and lysosomes. It also led to the upregulation of MHC class II molecules and TLRs 2, 3, 6, and 7. Additionally, the production of IL-4, IL-6, IL-8, and MCP-1 was significantly increased. Conclusions: Pulmonarom® promotes moDC maturation, characterized by enhanced antigen presentation capabilities and lysosomal activity, along with increased expression of specific TLRs and cytokines. These features suggest a trained immunity phenotype in moDCs, potentially improving their ability to initiate adaptive immune responses against respiratory pathogens. To our knowledge, this is the first study to investigate the immunomodulatory effects of Pulmonarom® on human moDCs, providing novel insights into its potential as an immunotherapeutic adjuvant.

A 58-year-old female with a medical history of type 2 diabetes mellitus and arterial hypertension, presented with 3 months history of multiple hyperpigmented macules in the labial mucosa, hard palate, and tongue without any associated symptoms [Figure 1]a and [Figure 1]b. The patient was a nonsmoker and denied the use of any new medication that could cause the pigmentation. Diagnosis Due to the clinical findings of multiple hyperpigmented macules in oral and labial mucosa associated with longitudinal melanonychia in the absence of systemic disease, the patient was diagnosed with LHS. Differential diagnoses of this entity include Peutz-Jeghers syndrome (PJS), Addison's disease, Albright syndrome, Bandler syndrome, Cronkhite-Canada syndrome, melanoma, drug induced pigmentation (phenytoin, zidovudine, antimalarials, clofazimine and phenothiazine), hiperpigmentation due to smoking or heavy metal exposure and oral lichen planus.

CD4 T cells are major players in the immune response against several diseases; including AIDS, leishmaniasis, tuberculosis, influenza and cancer. Their activation has been successfully achieved by administering antigen coupled with antibodies, against DC-specific receptors in combination with adjuvants. Unfortunately, most of the adjuvants used so far in experimental models are unsuitable for human use. Therefore, human DC-targeted vaccination awaits the description of potent, yet nontoxic adjuvants. The nontoxic cholera B subunit (CTB) can be safely used in humans and it has the potential to activate CD4 T cell responses. However, it remains unclear whether CTB can promote DC activation and can act as an adjuvant for DC-targeted antigens. Here, we evaluated the CTB's capacity to activate DCs and CD4 T cell responses, and to generate long-lasting protective immunity. Intradermal (i.d.) administration of CTB promoted late and prolonged activation and accumulation of skin and lymphoid-resident DCs. When CTB was co-administered with anti-DEC205-OVA, it promoted CD4 T cell expansion, differentiation, and infiltration to peripheral nonlymphoid tissues, i.e., the skin, lungs and intestine. Indeed, CTB promoted a polyfunctional CD4 T cell response, including the priming of Th1 and Th17 cells, as well as resident memory T (RM) cell differentiation in peripheral nonlymphoid tissues. It is worth noting that CTB together with a DC-targeted antigen promoted local and systemic protection against experimental melanoma and murine rotavirus. We conclude that CTB administered i.d. can be used as an adjuvant to DC-targeted antigens for the induction of broad CD4 T cell responses as well as for promoting long-lasting protective immunity.

Claire Kilroy attended the \"First Intensive Seminar Week on Irish Studies\" that Dr Pilar Villar Argáiz organised at the University of Granada (from 15th to 18th of December 2015), where the writer gave a talk about her latest novel, The Devil I Know. The aim of this interview was both to understand how the post-Celtic Tiger social context motivated not only the content of this novel but also its formal features, and to map the correlation between these two aspects. Kilroy also speaks about the political and cultural background of her book, her literary heritage, the creative process behind the composition of this novel, its characterisation devices and narrative structure, and her next writing projects. Key Words. Celtic Tiger Period, Contemporary Irish Literature, Claire Kilroy, Irish Fiction, Post-Celtic Tiger Literature. Claire Kilroy acudió al \"Primer Seminario Intensivo sobre Estudios Irlandeses\" organizado por la Dra. Pilar Villar Argáiz en la Universidad de Granada (del 15 al 18 de Diciembre de 2015), en el que la escritora irlandesa habló de su última novela, The Devil I Know. El objetivo de esta entrevista se centra en comprender el contenido de la novela así como sus características formales, todo ello originado por el contexto social de Irlanda tras el periodo conocido como Tigre Celta. Se buscará por tanto trazar la correlación entre ambos aspectos en la novela. Kilroy también habla aquí sobre el trasfondo cultural y político de su novela, sobre su herencia literaria, sobre el proceso creativo detrás de esta obra, sus mecanismos de caracterización y de estructura narrativa, y sobre sus próximos proyectos. Palabras clave. Periodo del Tigre Celta, literatura irlandesa contemporánea, Claire Kilroy, ficción irlandesa, literatura post-Tigre Celta.

Deforming nodular lesions in an indigenous person from western Mexico compatible with leishmaniasis. Graphical Abstract Graphical Abstract Deforming nodular lesions in an indigenous person from western Mexico compatible with leishmaniasis.

Salmonella enterica serovar Typhi (S. Typhi) porins, OmpC and OmpF, are potent inducers of the immune response against S. Typhi in mice and humans. Vaccination with porins induces the protection against 500 LD50 of S. Typhi, life-lasting bactericidal antibodies and effector T cell responses in mice; however, the nature of the memory T cell compartment and its contribution to protection remains unknown. In this work, we firstly observed that vaccination with porins induces in situ (skin) CD4+ and CD8+ T cell responses. Analysis of the porin-specific functional responses of skin CD4+ and CD8+ T cells showed IFN-gamma- and IL-17-producing cells in both T cell populations. The memory phenotype of porin-specific T cells indicated the presence of resident and effector memory phenotypes in the skin, and a central memory phenotype in the skin-draining lymph node. In addition, we demonstrated that vaccination with porins via skin reduces the bacterial burden following challenge. Finally, evaluating the role of the circulating T cell memory population in protection, we showed that circulating memory CD4+ and CD8+ T cells are crucial in porin-mediated protection against S. Typhi. Overall, this study highlights the importance of inducing circulating memory T cell responses in order to achieve the optimal protection provided by porins, showing a mechanism that could be sought in the rational development of vaccines.

Calciphylaxis, also known as calcific uremic arteriolopathy and uremic small artery disease with medial wall calcification and intimal hyperplasia, is a multifactorial cutaneous vascular disease characterized by chronic, painful, non-healing wounds that occur frequently in patients with chronic kidney disease, predominantly in those with end-stage renal disease. The pathogenesis remains unclear, and the development of calciphylaxis lesions depends on medial calcification, intimal fibrosis of arterioles and thrombotic occlusion. Despite an increase in reports of calciphylaxis in the literature and clinical recognition of demographic characteristics and risk factors associated with calciphylaxis, it remains a poorly understood disease with high morbidity and mortality. In this review, we analyze and summarize the clinical manifestations, pathogenesis and pathophysiology, histopathology, differential diagnosis, diagnostic workup and treatment modalities for calciphylaxis. Because of the lack of consensus regarding the optimal approach to and treatment of this disorder, a high degree of clinical suspicion, early diagnosis, and multimodal and multidisciplinary treatment in collaboration with dermatology, nephrology, wound care, nutrition and pain management specialties may improve survival in patients with calciphylaxis.

BackgroundThe pathophysiology of long-COVID remains unknown, and information is particularly limited for symptoms of very long duration. We aimed to assess the serological, T-cell immune responses and ANA titers of patients with long-COVID-19 syndrome of 1-year duration.MethodsProspective, longitudinal study of hospitalized COVID-19 patients followed-up for 12 months. Sequential blood samples and COVID-19 symptom questionnaires (CSQ) were obtained, and humoral and cellular immune responses, antinuclear antibodies (ANA) and inflammation biomarkers were analyzed.ResultsOf 154 patients discharged from hospital, 72 non-vaccinated with available CSQ in all visits were included. Of them, 14 (19.4%) reported persistent symptoms both at 6-months and 12-months, mainly asthenia (15.3%), myalgia (13.9%), and difficulty concentrating/memory loss (13.9%). Symptomatic patients were more frequently women, smokers, showed higher WHO severity score, and a trend to higher ICU admission. In the adjusted analysis, long-COVID syndrome was associated with lower frequency of detectable neutralizing antibodies (adjusted hazard ratio [aHR] 0.98; 95% confidence interval [CI], 0.97-0.99) and lower SARS-CoV-2-S1/S2 titers (aHR [95%CI] 0.14 [0.03–0.65]). T-cell immune response measured with a SARS-CoV-2-interferon-γ release assay was not different between groups. There was a higher frequency of positive ANA titers (≥160) in symptomatic patients (57.1% vs 29.3%, p=0.04), that was attenuated after adjustment aHR [95% CI] 3.37 [0.84-13.57], p=0.087. Levels of C-reactive protein and D-dimer were higher during follow-up in symptomatic patients, but with no differences at 12 months.ConclusionPatients with 1-year duration long-COVID-19 syndrome exhibit a distinct immunologic phenotype that includes a poorer SARS-CoV-2 antibody response, low-degree chronic inflammation that tends to mitigate, and autoimmunity.