Stevens-Johnson syndrome and toxic epidermal necrolysis: a review

Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are considered a single entity with variability in the extent of the lesions, characterized by erythema multiforme that may involve mucosa. Severe cutaneous reactions secondary to medications are classified according to the area of epidermal detachment. The activation of cytotoxic T cells and macrophages is mediated mainly by IL-2 and interferon gamma secreted by Th1 lymphocytes, and the activation of eosinophils and B lymphocytes in IgE is mediated by secreted IL-4, IL-5, IL-10 and IL13 by B lymphocytes. The topography of SJS is predominantly central, affecting the trunk and sometimes a generalized dissemination is shown that affects a body surface area of less than 10%, characterized by irregular violaceous erythematous macules of target shooting, which can form confluent blisters. TEN is characterized by a skin detachment greater than 30% of the body surface, whose predominant lesion is diffuse erythema with individual macules, which give rise to detachment surfaces greater than 5 cm. The treatment is symptomatic, nonspecific, and aimed at avoiding complications, carried out in specialized intensive care units, due to ignorance of the pathogenesis. Integral management with different therapeutic alternatives can represent a crucial part in the multisystemic management of SJS and TEN

TGFβ Governs the Pleiotropic Activity of NDRG1 in Triple-Negative Breast Cancer Progression

In triple-negative breast cancer (TNBC), the pleiotropic NDRG1 (N-Myc downstream regulated gene 1) promotes progression and worse survival, yet contradictory results were documented, and the mechanisms remain unknown. Phosphorylation and localization could drive NDRG1 pleiotropy, nonetheless, their role in TNBC progression and clinical outcome was not investigated. We found enhanced p-NDRG1 (Thr346) by TGFβ1 and explored whether it drives NDRG1 pleiotropy and TNBC progression. In tissue microarrays of 81 TNBC patients, we identified that staining and localization of NDRG1 and p-NDRG1 (Thr346) are biomarkers and risk factors associated with shorter overall survival. We found that TGFβ1 leads NDRG1, downstream of GSK3β, and upstream of NF-κB, to differentially regulate migration, invasion, epithelial-mesenchymal transition, tumor initiation, and maintenance of different populations of cancer stem cells (CSCs), depending on the progression stage of tumor cells, and the combination of TGFβ and GSK3β inhibitors impaired CSCs. The present study revealed the striking importance to assess both total NDRG1 and p-NDRG1 (Thr346) positiveness and subcellular localization to evaluate patient prognosis and their stratification. NDRG1 pleiotropy is driven by TGFβ to differentially promote metastasis and/or maintenance of CSCs at different stages of tumor progression, which could be abrogated by the inhibition of TGFβ and GSK3β.Instituto de Salud Carlos III European Commission PI15/00336 PI19/01533 CP14/00197 CP19/00029 PIE16/00045Ministry of Science and Innovation, Spain (MICINN)Instituto de Salud Carlos IIISpanish Government RTI2018.101309B-C22Chair "Doctors Galera-Requena in cancer stem cell research" CMC-CTS963European Regional Development Fund (European Union)Ministerio de Universidades FPU19/04450Junta de Andalucia RH-0139-2020Sistema Nacional de Garantia Juvenil (Fondo Social Europeo) 8064Junta de Andalucia, Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades DOC_01686Fundacion Cientifica Asociacion Espanola Contra el Cancer, Junta Provincial de Jaen (AECC) PRDJA19001BLA

Antebrachial microvascular flap for reconstruction of the pelvic limb: case report

Complex defects in the soft tissues of the foot and ankle caused by high-energy trauma, infection, cancer or diabetes require rapid and effective treatment which decreases the risk of infection, bone healing time, hospital stay and number total of surgical approaches. Authors report a clinical case of a 23-year-old female patient who suffers high-energy trauma due to a motorcycle accident which causes exposure of the distal third of the tibia, loss of the tibial joint face, and loss of tissue throughout the region of the malleolus medial of the right pelvic extremity. Tissue transfer to the pelvic limb is performed using left contralateral radial antebrachial free flap as donor area. This case report aims to emphasize the key aspects of the high energy trauma approach by using microvascular flaps, as well as the satisfactory evolution of the patient that directly affects the prognosis for life and function

Long term measurement of the 222Rn concentration in the Canfranc Underground Laboratory

We report the results of 6 years (2013–2018) of measurements of 222Rn air concentration, relative humidity, atmospheric pressure and temperature in the halls A, B and C of the Canfranc Underground Laboratory (LSC). We have calculated all the Pearson correlation coefficients among these parameters and we have found a positive correlation between the 222Rn concentration and the relative humidity. Both correlated variables show a seasonal periodicity. The joint analysis of laboratory data and 4 years (2015– 2018) of the meteorological variables outside the laboratory shows the correlation between the 222Rn concentration and the outside temperature. The collected information stresses the relevance of designing good Rn-mitigation strategies in current and future experiments at LSC; in particular, we have checked for two years (2017–2018) the good performance of the mitigation procedure of the ANAIS-112 experiment. Finally, we have monitored (2019–2021) for 2 years of live time, the radon-free air provided by the radon abatement system installed in the laboratory.This research was funded by MCIN/AEI/10.13039/501100011033 under Grant PID2019-104374GB-I00; by MINECO-FEDER under Grants FPA2017-83133-P, and FPA2014-55986-P; by MICINN-FEDER under Grants FPA2011-23749; by CONSOLIDER-Ingenio 2010 Programme under Grants MultiDark CSD2009-00064 and CPAN CSD2007-00042; by the University of Zaragoza under Grant UZ2017-CIE-09; by the Spanish Meteorological Agency (AEMET), the Gobierno de Aragón (Group in Nuclear and Astroparticle Physics, ARAID Foundation and I. Coarasa predoctoral grant), the European Social Fund and by the LSC consortium

Towards a synthetic tutor assistant: The EASEL project and its architecture

Robots are gradually but steadily being introduced in our daily lives. A paramount application is that of education, where robots can assume the role of a tutor, a peer or simply a tool to help learners in a specific knowledge domain. Such endeavor posits specific challenges: affective social behavior, proper modelling of the learner’s progress, discrimination of the learner’s utterances, expressions and mental states, which, in turn, require an integrated architecture combining perception, cognition and action. In this paper we present an attempt to improve the current state of robots in the educational domain by introducing the EASEL EU project. Specifically, we introduce the EASEL’s unified robot architecture, an innovative Synthetic Tutor Assistant (STA) whose goal is to interactively guide learners in a science-based learning paradigm, allowing us to achieve such rich multimodal interactions

Relapse of unusual localization of classic seminoma with post-chemotherapy transformation

Germ cell tumor is the most common cancer among males in the 20–39 year-old age range, representing 21% of invasive cancer diagnose. The vast majority of testicular tumors in this age range are germ cell tumors. There are two types of malignant tumors, the pure seminoma cell and non-seminomatous germinal cell tumors (NGCT). We present the case of a patient who underwent a testicular tumor surgery, classic seminoma stage I, receiving two cycles of adjuvant carboplatin chemotherapy. During the follow up, an elevation on the alpha-fetoprotein level was observed, thus the final diagnosis was adenopatic recurrence of the Yolk Sac tumor.-----------------------------------------------------------------Cite this article as: Urena MD, Legeren M, Galvez F, Villaescusa A, Aparicio J, Jurado JM, Blancas I, Sanchez MJ, Romera AL, Martinez AP, Quiñonez E, Dulcey I, Puche JL. Relapse of unusual localization of classic seminoma with post-chemotherapy transformation. Int J Cancer Ther Oncol 2014; 2(1):02016.DOI: http://dx.doi.org/10.14319/ijcto.0201.

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2

We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo hACE2 decoys to neutralize SARS-CoV-2. The best decoy, CTC-445.2, binds with low nanomolar affinity and high specificity to the RBD of the spike protein. Cryo-EM shows that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, shows ~10-fold improvement in binding. CTC-445.2d potently neutralizes SARS-CoV-2 infection of cells in vitro and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge

Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin

The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes of life-threatening necrosis, typically triggered by S. aureus infection. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of linear ubiquitin in dermal fibroblasts, but tumor necrosis factor receptor-mediated nuclear factor kappa B signaling remains intact. Blood leukocyte subsets are unaffected. The OTULIN-dependent accumulation of caveolin-1 in dermal fibroblasts, but not leukocytes, facilitates the cytotoxic damage inflicted by the staphylococcal virulence factor alpha-toxin. Naturally elicited antibodies against alpha-toxin contribute to incomplete clinical penetrance. Human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to alpha-toxin in nonleukocytic cells.Peer reviewe

Inter-Rater Variability in the Evaluation of Lung Ultrasound in Videos Acquired from COVID-19 Patients

12 páginas, 7 figuras, 1 tablaLung ultrasound (LUS) allows for the detection of a series of manifestations of COVID-19, such as B-lines and consolidations. The objective of this work was to study the inter-rater reliability (IRR) when detecting signs associated with COVID-19 in the LUS, as well as the performance of the test in a longitudinal or transverse orientation. Thirty-three physicians with advanced experience in LUS independently evaluated ultrasound videos previously acquired using the ULTRACOV system on 20 patients with confirmed COVID-19. For each patient, 24 videos of 3 s were acquired (using 12 positions with the probe in longitudinal and transverse orientations). The physicians had no information about the patients or other previous evaluations. The score assigned to each acquisition followed the convention applied in previous studies. A substantial IRR was found in the cases of normal LUS (κ = 0.74), with only a fair IRR for the presence of individual B-lines (κ = 0.36) and for confluent B-lines occupying 50% (κ = 0.50). No statistically significant differences between the longitudinal and transverse scans were found. The IRR for LUS of COVID-19 patients may benefit from more standardized clinical protocols.This research was partially funded by CDTI (Spanish acronym: Centre for Industrial Tech- nological Development), funding number COI-20201153. Partially supported by the Google Cloud Research Credits program with the funding number GCP19980904, by the project RTI2018-099118- A-I00 founded by MCIU/AEI/FEDER UE and by the European Commission–NextGenerationEU, through CSIC’s Global Health Platform (PTI Salud Global)