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Partial mitochondrial involvement in the antiproliferative and immunostimulatory effects of PT-112
Get PDFPT-112 is a novel small molecule exhibiting promising clinical activity in patients with solid tumors. PT-112 kills malignant cells by inhibiting ribosome biogenesis while promoting the emission of immunostimulatory signals. Accordingly, PT-112 is an authentic immunogenic cell death (ICD) inducer and synergizes with immune checkpoint inhibitors in preclinical models of mammary and colorectal carcinoma. Moreover, PT-112 monotherapy has led to durable clinical responses, some of which persisting after treatment discontinuation. Mitochondrial outer membrane permeabilization (MOMP) regulates the cytotoxicity and immunogenicity of various anticancer agents. Here, we harnessed mouse mammary carcinoma TS/A cells to test whether genetic alterations affecting MOMP influence PT-112 activity. As previously demonstrated, PT-112 elicited robust antiproliferative and cytotoxic effects against TS/A cells, which were preceded by the ICD-associated exposure of calreticulin (CALR) on the cell surface, and accompanied by the release of HMGB1 in the culture supernatant. TS/A cells responding to PT-112 also exhibited eIF2α phosphorylation and cytosolic mtDNA accumulation, secreted type I IFN, and exposed MHC Class I molecules as well as the co-inhibitory ligand PD-L1 on their surface. Acute cytotoxicity and HMGB1 release caused by PT-112 in TS/A cells were influenced by MOMP competence. Conversely, PT-112 retained antiproliferative effects and its capacity to drive type I IFN secretion as well as CALR, MHC Class I and PD-L1 exposure on the cell surface irrespective of MOMP defects. These data indicate a partial involvement of MOMP in the mechanisms of action of PT-112, suggesting that PT-112 is active across various tumor types, including malignancies with MOMP defects
Perceptions and Experiences of a Multimodal Rehabilitation Program for People With Post‐Acute COVID‐19: A Qualitative Study
Get PDFIntroduction. Home‑based rehabilitation has emerged as a practical solution for post‑acute phase COVID‑19 recovery, but patient perspectives on the different modalities remain underexplored.ObjectiveTo explore participants' perceptions and experiences after a 12‑week multimodal rehabilitation program delivered via asynchronous telerehabilitation versus a booklet after discharge and to identify the preferred format.MethodsQualitative descriptive study with two face‑to‐face focus groups of post‐discharge COVID‐19 patients (n = 12; age range 41–75 years; 50% female; with fatigue > 4 on the Fatigue Severity Scale) that included participants from each intervention arm of a randomised pilot study. Semi‑structured interviews to determine patients' perceptions and experiences were recorded, transcribed verbatim and coded independently by two researchers using inductive thematic analysis.ResultsThree overarching themes emerged from the analysis: (1) Facilitators for engagement and adherence: Innovative digital tools and personalised guidance foster active participation by providing flexible access and systematic progress monitoring; (2) Barriers to sustained participation: Technological issues, physical limitations and fluctuating motivation serve as critical impediments, underscoring the potential benefits of hybrid intervention models; and (3) Therapeutic alliance as support: A robust, individualised therapeutic relationship enhances patient confidence and self‐management, ultimately contributing to sustained empowerment and recovery.ConclusionsA multimodal home‐based rehabilitation program with monitoring and personalisation by the physiotherapist is rated positively by post‐acute COVID‐19 patients, with asynchronous telerehabilitation emerging as the preferred method. Future research should investigate long‑term adherence, clinical efficacy and scalability.Clinical Trial RegistrationClinialtrials.gov #NCT04794036.Patient or Public ContributionPost‐acute COVID‐19 patients contributed to the study by actively participating in its development, specifically through describing their experiences as part of a multimodal rehabilitation program. There was no additional participation or contribution from the public to the research
Controls on carbonate deposition and microbialite formation in distal alluvial systems (Campanian, Montalbán subbasin, NE Spain)
Get PDFThe middle-upper Campanian Allueva Formation was deposited in the compressional intramountain Montalbán subbasin (central Iberian Ranges, NE Spain). This i.e. formation consists of alluvial terrigenous deposits, with local dominance of carbonates and microbialites, which are the main focus of this study. Three sfacies associations are differentiated: i) bioclastic facies association including limestone levels with accumulation of gastropods and charophytes, along with polygenetic carbonate breccias; ii) microbialite facies association dominated by irregular limestone beds rich in oncoids; iii) terrigenous facies association including metric levels of reddish-brown mudstone with intercalations of sandstones and conglomerates. These facies deposited in a low water level and short residence lacustrine-palustrine environments, in the distal areas of an alluvial system. Isotopic data (δ13C and δ18O) fall in the range of freshwater carbonates and support this interpretation. The most common microbialites are oncoids, which have been classified into six types based on their morphology, size, and lamination. Cyclic patterns in the lamination of oncoids have been related to changing wet and dry conditions. Our results suggest that the alluvial setting was mainly fed by meteoric waters, with a sub-humid climate gradually transitioning to more arid conditions
Identification of the methionine transporter MetQ in Streptococcus suis and its contribution to virulence and biofilm formation
Get PDFStreptococcus suis is a Gram-positive bacterium responsible for various infections in both pigs and humans. This study investigates the role of methionine acquisition in the growth and virulence of S. suis. The putative methionine transport system is organised as an operon comprising the metQ gene and genes encoding a transposase and an ATPase, forming a typical tripartite ABC transporter. This operon is conserved across multiple streptococcal species, including both animal and human pathogens. We examined whether MetQ functions as a methionine-binding protein and its role in bacterial infection. Using Western blotting and flow cytometry with a specific antiserum, we demonstrated that MetQ is produced in vitro by the S. suis reference strain P1/7 under methionine-limited conditions and is located on the bacterial cell surface. Growth assays in chemically defined media revealed that a metQ deletion mutant (P1/7∆metQ) exhibited impaired growth under methionine-restricted conditions but grew normally in a nutrient-rich medium, suggesting that MetQ primarily transports methionine. Isothermal Titration Calorimetry demonstrated that MetQ binds L-methionine with a dissociation constant (KD) of 7.1 µM. In a murine infection model, the metQ mutant showed reduced dissemination to internal organs compared to the wild type. Furthermore, the mutant showed decreased intracellular survival in murine macrophages and increased sensitivity to oxidative stress, while exhibited enhanced biofilm formation compared to the wild type. Our findings indicate that MetQ is essential for methionine uptake under methionine-restricted conditions, which is critical for bacterial nutrition, immune evasion, and pathogenicity during infection
Molecular identification of Coranus spp. in a pregnant patient: A case of misidentified Chagas disease vector in Spain
Get PDFChagas disease is a significant public health concern in the Americas, transmitted primarily by vectors of the Triatominae subfamily. While Europe, particularly Spain, is free from endemic vectors, the potential for misidentification of non-hematophagous insects as Chagas vectors exists, leading to unnecessary alarm. We present the case of a 31-year-old pregnant Venezuelan woman residing in Spain, who sought medical attention after being bitten by an arthropod she identified as Triatoma infestans. The patient's awareness of Chagas disease in her country of origin heightened her concern about vertical transmission of Trypanosoma cruzi to her fetus. However, serological testing for T. cruzi antibodies was negative. The insect was initially misidentified as T. infestans but was later confirmed through molecular analysis to be Coranus spp., a non-hematophagous reduviid predator. The 18S rRNA gene sequence revealed a 99.37 % similarity to Coranus spp., ruling out any vectorial capacity for Chagas disease. This case underscores the importance of accurate arthropod identification, especially in non-endemic regions, to prevent misdiagnosis and unnecessary treatment. From a public health perspective, the introduction of a Chagas disease vector into Spain would represent a serious threat, necessitating prompt identification and containment measures. Our findings highlight the challenges posed by invasive species and the need for vigilance in regions where Chagas disease is not endemic. Proper identification of suspected vectors is crucial to ensure appropriate clinical and public health responses, preventing unwarranted anxiety and ensuring accurate disease surveillance
Influence of intermediate abutment height and timing of placement on marginal bone loss in single implant-supported crowns: a 12-month follow-up randomized clinical trial
Get PDFObjectives: To determine the most effective combination of abutment height and timing of placement in reducing marginal bone loss (MBL). Materials and methods: 54 patients received at least one single screw-retained crown on an implant replacing a posterior tooth (60 implants). Implants were divided into six groups based on intermediate abutment height (1.5 mm, 2 mm, 3 mm) and timing of placement (immediate: surgery 1; delayed: surgery 2): Group A3I (height 3, surgery 1), Group A2I (height 2, surgery 1), Group A15I (height 1.5, surgery 1), Group A3D (height 3, surgery 2), Group A2D (height 2, surgery 2), Group A15D (height 1.5, surgery 2). Mesial and distal linear radiographic measurements were taken at five follow-up points: implant surgery, crown placement (T1), and 3 (T2), 6 (T3), and 12 months after loading (T4). Partial and total MBL were compared between groups. Results: After 12 months, the lowest MBL was found in groups A3I (0.13 ± 0.11 mm) and A2I (0.24 ± 0.11 mm), with no statistical difference between them. Groups A15I (0.70 ± 0.12 mm), A3D (0.66 ± 0.11 mm), A2D (0.62 ± 0.12 mm), and A15D (0.78 ± 0.11 mm) showed significantly higher MBL than groups 1 and 2, with no statistical difference among them. Conclusions: Immediate abutments of 2–3 mm resulted in lower MBL compared to 1.5 mm immediate abutments or any delayed abutments
El Libro del conoscimiento de todos los reinos, 25 años después (1999-2024)
Get PDFThe article reviews the main contributions on the The Book of Knowledge of All Kingdoms from 1999, when it was reissued simultaneously in two editions, to the present day, with special attention to the Canary Islands and Le Canarien. In contrast to 19th-century criticism, the current bibliography is less concerned with the authenticity of the narration and the identity of the author, although erroneous information is sometimes repeated. Today, critics are more interested in the conception of space, the relationship with other travel books and the perception of the Orient. Finally, the work focuses on the illustrated book Le frère mendiant, which includes extracts from The Book of Knowledge and drawings by Pablo Picasso.
En el artículo se revisan las principales aportaciones sobre el Libro del conoscimiento de todos los reinos desde 1999, fecha en la que se reeditó simultáneamente en dos ediciones, hasta la actualidad, con especial atención a lo referido a las islas Canarias y a Le Canarien. Frente a la crítica del siglo xix, la bibliografía más reciente se preocupa menos de la autenticidad de lo narrado y de la identidad del autor, aunque siguen repitiéndose a veces datos erróneos. Hoy interesa más la concepción del espacio, la relación con otros libros de viajes y la percepción de Oriente. Por último, el trabajo se centra en el libro ilustrado Le frère mendiant, que incluye extractos del Libro del conoscimiento junto a dibujos de Pablo Picasso
Core–shell powder strategy for additive manufacturing of ceramics: application to direct powder bed selective laser processing of silicon carbide
Get PDFThe production of innovative ceramic powders through surface functionalization of grains, featuring a core–shell structure, accelerates mass diffusion and enhances sintering behavior. This approach significantly impacts the additive manufacturing field. In this study, a commercial SiC preceramic compound from the polycarbosilane family, specifically poly(silaethylene), was grafted onto the surface of Silicon Carbide (SiC) particles, forming a conformal molecular layer. Powder Bed Selective Laser Processing, also known as Selective Laser Sintering/Melting, was employed to fabricate 3D SiC and surface-modified SiC parts, enabling a comparative analysis of the efficiency and impact of surface modification in the manufacturing process. The surface functionalization increases densification by at least 5% without affecting the final phases of the manufactured parts. Additionally, Spark Plasma Sintering (SPS) was employe as a post-treatment to further densify the samples, increasing their final density and eliminating residual silicon and carbon, which are produced due to the undesired decomposition of SiC during the manufacturing process
Aspectos nutricionales de los pacientes con parálisis cerebral: un estudio observacional y multicéntrico en España
No full textIntroducción: La parálisis cerebral (PC) abarca un grupo de trastornos motores que pueden resultar en dificultades para tragar, afectando la ingesta de alimentos y contribuyendo a un deterioro del estado nutricional. El objetivo del estudio fue describir las características clínicas y nutricionales de los niños españoles con PC.
Métodos: Estudio observacional multicéntrico realizado en niños de 4 a 14 años diagnosticados de PC. Se recopilaron datos sociodemográficos y clínicos, así como medidas antropométricas, modalidad escolar, nutrición recibida en la escuela, apoyo nutricional y comorbilidades gastrointestinales de todos los pacientes.
Resultados: Se incluyó un total de 112 pacientes con una edad media de 9,2 años. Un 70,5% presentaba un grado IV-V en el Sistema de Clasificación de la Función Motora Gruesa (GMFCS). En comparación con aquellos con GMFCS I-II-III, los niños con grados IV-V del GMFCS mostraron una puntuación z media significativamente menor en peso, talla, relación peso/talla, índice de masa corporal y circunferencia del brazo, y un área del brazo significativamente menor. Una proporción mayor de pacientes con GMFCS IV-V asistió a escuelas de educación especial en comparación con pacientes con GMFCS I-II-III (68,4% vs. 12,1%, p < 0,0001). Una mayor proporción de niños con GMFCS IV-V presentó disfagia (62,0% vs. 15,2%, p < 0,0001), estreñimiento (51,9% vs. 27,3%, p = 0,0218) y reflujo gastroesofágico (31,6% vs. 3,0%, p = 0,0005) en comparación con niños con GMFCS I-II-III.
Conclusiones: Nuestro estudio muestra que los niños españoles con PC, especialmente aquellos con mayor deterioro motor grave, están en riesgo de desnutrición, presentan comorbilidades gastrointestinales y requieren apoyo nutricional
Clima motivacional entre jugadores y familias en categorías de fútbol base
Get PDFEn la actualidad, la psicología deportiva ha cobrado una importancia destacada al reconocer cómo las variables psicológicas y el entorno social y familiar influyen en la motivación, el rendimiento y la continuidad en la práctica deportiva del niño. La presente investigación se centra en la comparación de la evolución de los climas motivacionales entre jugadores y familias en etapas formativas en diversas categorías de fútbol base, abarcando desde benjamín (sub-8) hasta cadete (sub-16), ambas inclusive. La muestra está conformada por 1692 jugadores y familias (Benjamín = 299, Alevín = 496, Infantil = 454 y Cadete = 443), repartidos en las máximas categorías de 7 clubes de fútbol base de la ciudad de Zaragoza (España), utilizando un cuestionario ad-hoc compuesto por las dimensiones tarea y ego de la Escala de Metas de Logro para Deportes Juveniles y su adaptación para las familias de los jugadores. Los resultados revelaron que los jugadores presentan una orientación hacia un clima de tarea en las categorías inferiores (4.69±.38), mientras que las familias mantienen una orientación al ego desde las primeras categorías, incrementándose en las etapas superiores (4.34±.61). La principal conclusión de esta investigación fue que las diferencias en la percepción del clima motivacional entre jugadores y familias subrayan la necesidad de implementar programas educativos en los clubes de base orientados, principalmente, a las familia