Efectividad de guselkumab en pacientes con hidradenitis supurativa en condiciones de práctica clínica: estudio retrospectivo y multicéntrico en España

Biologics; Hidradenitis suppurativa; GuselkumabProductos biológicos; Hidradenitis supurativa; GuselkumabBiològics; Hidradenitis supurativa; GuselkumabBackground: Hidradenitis suppurativa (HS) is a chronic skin condition causing lesions in which high levels of interleukin (IL)-23 and T-helper 17 cells are found. Adalimumab remains the only approved treatment. Guselkumab, an antibody targeting the p19 protein subunit of extracellular IL-23, is approved for the treatment of moderate-severe psoriasis, but evidence on its efficacy in treating HS is limited. Objectives: To assess the effectiveness and safety of guselkumab in treating moderate-severe HS under clinical practice conditions. Methods: A multicentre retrospective observational study was carried out in 13 Spanish Hospitals including adult HS patients treated with guselkumab within a compassionate use programme (March 2020-March 2022). Data referred to patient demographic and clinical characteristics at treatment initiation (baseline), patient-reported outcomes (Numerical Pain Rating Scale [NPRS] and Dermatology Life Quality Index [DLQI]), physician scores (International Hidradenitis Suppurativa Severity Score System [IHS4], HS Physical Global Score [HS-PGA] and Hidradenitis Suppurativa Clinical Response [HiSCR]) were recorded at baseline and at 16, 24, and 48 weeks of treatment. Results: A total of 69 patients were included. Most (84.10%) had severe HS (Hurley III) and had been diagnosed for over ten years (58.80%). The patients had been subjected to multiple non-biological (mean 3.56) or biological (mean 1.78) therapies, and almost 90% of those treated with biologics had received adalimumab. A significant decrease in IHS4, HS-PGA, NPRS, and DLQI scores was observed from baseline to 48 weeks of guselkumab treatment (all p<0.01). HiSCR was achieved in 58.33% and 56.52% of the patients at 16 and 24 weeks, respectively. Overall, 16 patients discontinued treatment, mostly due to inefficacy (n=7) or loss of efficacy (n=3). No serious adverse events were observed. Conclusions: Our results indicate that guselkumab may be a safe and effective therapeutic alternative for patients with severe HS that fail to respond to other biologics

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Independent evolution of shape and motility allows evolutionary flexibility in Firmicutes bacteria

Functional morphological adaptation is an implicit assumption across many ecological studies. However, despite a few pioneering attempts to link bacterial form and function, functional morphology is largely unstudied in prokaryotes. One intriguing candidate for analysis is bacterial shape, as multiple lines of theory indicate that cell shape and motility should be strongly correlated. Here we present a large-scale use of modern phylogenetic comparative methods to explore this relationship across 325 species of the phylum Firmicutes. In contrast to clear predictions from theory, we show that cell shape and motility are not coupled, and that transitions to and from flagellar motility are common and strongly associated with lifestyle (free-living or host-associated). We find no association between shape and lifestyle, and contrary to recent evidence, no indication that shape is associated with pathogenicity. Our results suggest that the independent evolution of shape and motility in this group might allow a greater evolutionary flexibility

Disease Severity in Patients Infected with Leishmania mexicana Relates to IL-1β

Leishmania mexicana can cause both localized (LCL) and diffuse (DCL) cutaneous leishmaniasis, yet little is known about factors regulating disease severity in these patients. We analyzed if the disease was associated with single nucleotide polymorphisms (SNPs) in IL-1β (−511), CXCL8 (−251) and/or the inhibitor IL-1RA (+2018) in 58 Mexican mestizo patients with LCL, 6 with DCL and 123 control cases. Additionally, we analyzed the in vitro production of IL-1β by monocytes, the expression of this cytokine in sera of these patients, as well as the tissue distribution of IL-1β and the number of parasites in lesions of LCL and DCL patients. Our results show a significant difference in the distribution of IL-1β (−511 C/T) genotypes between patients and controls (heterozygous OR), with respect to the reference group CC, which was estimated with a value of 3.23, 95% CI = (1.2, 8.7) and p-value = 0.0167), indicating that IL-1β (−511 C/T) represents a variable influencing the risk to develop the disease in patients infected with Leishmania mexicana. Additionally, an increased in vitro production of IL-1β by monocytes and an increased serum expression of the cytokine correlated with the severity of the disease, since it was significantly higher in DCL patients heavily infected with Leishmania mexicana. The distribution of IL-1β in lesions also varied according to the number of parasites harbored in the tissues: in heavily infected LCL patients and in all DCL patients, the cytokine was scattered diffusely throughout the lesion. In contrast, in LCL patients with lower numbers of parasites in the lesions, IL-1β was confined to the cells. These data suggest that IL-1β possibly is a key player determining the severity of the disease in DCL patients. The analysis of polymorphisms in CXCL8 and IL-1RA showed no differences between patients with different disease severities or between patients and controls

Autopsy analyses in acute exacerbation of idiopathic pulmonary fibrosis

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with high mortality. However, few studies have so far reviewed analyses of autopsy findings in patients with AE-IPF.Methods: We retrospectively reviewed 52 consecutive patients with AE-IPF who underwent autopsies at five university hospitals and one municipal hospital between 1999 and 2013. The following variables were abstracted from the medical records: demographic and clinical data, autopsy findings and complications during the clinical course until death.Results: The median age at autopsy was 71 years (range 47-86 years), and the subjects included 38 (73.1%) males. High-dose corticosteroid therapy was initiated in 45 (86.5%) patients after AE-IPF. The underling fibrotic lesion was classified as having the usual interstitial pneumonia (UIP) pattern in all cases. Furthermore, 41 (78.8%) patients had diffuse alveolar damage (DAD), 15 (28.8%) exhibited pulmonary hemorrhage, nine (17.3%) developed pulmonary thromboembolism and six (11.5%) were diagnosed with lung carcinoma. In addition, six (11.5%) patients developed pneumothorax prior to death and 26 (53.1%) developed diabetes that required insulin treatment after the administration of high-dose corticosteroid therapy. In addition, 15 (28.8%) patients presented with bronchopneumonia during their clinical course and/or until death, including fungal (seven, 13.5%), cytomegalovirus (six, 11.5%) and bacterial (five, 9.6%) infections.Conclusions: The pathological findings in patients with AE-IPF represent not only DAD, but also a variety of pathological conditions. Therefore, making a diagnosis of AE-IPF is often difficult, and the use of cautious diagnostic approaches is required for appropriate treatment

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Diseño estratégico de vanguardia

La integración del diseño con la vanguardia se observa natural, esto es, el diseño es una disciplina abductiva y la vanguardia persigue fines prospectivos, es decir, en ambos casos se trata de objetivos de posibilidad futura. De tal suerte, este libro, emanado de una parte de las ponencias rigurosamente arbitradas del Coloquio Internacional de Diseño 2016, está dividido en tres secciones o capítulos, a saber, el capítulo uno relacionado con la teoría y metodología para proyectos de diseño de vanguardia, el segundo sobre la tecnología, la innovación y la sostenibilidad de vanguardia de dichos proyectos, y finalmente el último capítulo, vinculado con la gestión estratégica de proyectos de vanguardia.La historia se forja de hechos e interpretaciones, de pasados construidos y de presentes en procesos constantes, estudiados en forma estricta por las ciencias. Por su parte, el futuro ostenta la posibilidad de ser indefinidamente planeado con base en las variopintas aproximaciones teóricas y empíricas que dan fundamento a este tipo de ciencia; éstas son denominadas prospectivas y sus bases vanguardias. Resulta importante señalar, que estas posibilidades sólo permiten tener una idea hipotética de lo que será la realidad y el mundo de vida de los seres vivos y su contexto, no obstante, se trata de la única manera racional que tiene el ser humano de prever ese futuro posible. Las distintas ciencias y disciplinas nos permiten construir históricamente estas posibilidades partiendo de datos, hechos, significados y un sinfín de informaciones que le dan cuerpo y sentido a tales posibilidades. En este sentido, la vanguardia, como base del conocimiento prospectivo, observa la necesidad de ser escrita, leída y discutida en los términos más estrictos con el fin de volver las predicciones más precisas. El diseño por su parte, es definido de manera sucinta como la disciplina proyectual estratégica y sistémica de la posibilidad, dirigida a procesos de significación utilitaria y simbólica para la comprensión –o interpretación– y modificación –o proyectación– de niveles de realidad (referentes y sujetos) desde diversos aparatos teóricos y empíricos –perspectivas disciplinarias–

New experimental models of skin homeostasis and diseases

[ES]: La homeostasis de la piel, cuya regulación molecular es aún bastante desconocida, está íntimamente relacionada con la función de las células madre epidérmicas. El programa SkinModel-CM, auspiciado por la Comunidad de Madrid, reúne 5 grupos de investigación con el propósito de desarrollar nuevos modelos experimentales in vitro e in vivo para analizar la función de ADN metiltransferasa 1, la endoglina y la podoplanina en la actividad de las células madre epidérmicas y en la homeostasis y el cáncer cutáneos. Estos nuevos modelos comprenden tanto cultivos organotípicos 3 D, como ratones inmunodeficientes con la piel humanizada y ratones modificados genéticamente. Otro objetivo del programa es el uso de ratones con la piel humanizada como modelo para reconstruir enfermedades cutáneas, tales como el síndrome de Gorlin y el xeroderma pigmentoso, con el objeto de optimizar nuevos protocolos de intervención mediante la terapia fotodinámica[EN]: Homeostasis, whose regulation at the molecular level is still poorly understood, is intimately related to the functions of epidermal stem cells. Five research groups have been brought together to work on new in vitro and in vivo skin models through the SkinModel-CM program, under the auspices of the Spanish Autonomous Community of Madrid. This project aims to analyze the functions of DNA methyltransferase 1, endoglin, and podoplanin in epidermal stem cell activity, homeostasis, and skin cancer. These new models include 3-dimensional organotypic cultures, immunodeficient skin-humanized mice, and genetically modified mice. Another aim of the program is to use skin-humanized mice to model dermatoses such as Gorlin syndrome and xeroderma pigmentosum in order to optimize new protocols for photodynamic therapy.El consorcio SkinModel-CM está financiado por la Comunidad de Madrid (programa S2010/BMD-2359).Peer Reviewe