Pseudomonas aeruginosa bloodstream infections in children and adolescents: risk factors associated with carbapenem resistance and mortality.

BACKGROUND: Pseudomonas aeruginosa bloodstream infections (PA-BSIs) are a serious disease and a therapeutic challenge due to increasing resistance to carbapenems. Our objectives were to describe the prevalence and risk factors associated with carbapenem resistance (CR) and mortality in children with PA-BSI. METHODS: A retrospective, multi-centre study was carried out, including patients aged <20 years with PA-BSI in four tertiary hospitals in Madrid (Spain) during 2010-2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multi-variable logistic regression model. RESULTS: In total, 151 patients with PA-BSI were included, with a median age of 29 months (interquartile range: 3.5-87.1). Forty-five (29.8%) cases were CR, 9.9% multi-drug resistant and 6.6% extensively drug resistant. The prevalence of CR remained stable throughout the study period, with 26.7% (12/45) of CR mediated by VIM-type carbapenemase. Patients with BSIs produced by CR-PA were more likely to receive inappropriate empiric treatment (53.3% vs 5.7%, P<0.001) and to have been previously colonized by CR-PA (8.9% vs 0%, P=0.002) than BSIs caused by carbapenem-susceptible P. aeruginosa. CR was associated with carbapenem treatment in the previous month (adjusted odds ratio (aOR) 11.15) and solid organ transplantation (aOR 7.64). The 30-day mortality was 23.2%, which was associated with mechanical ventilation (aOR 4.24), sepsis (aOR 5.72), inappropriate empiric antibiotic therapy (aOR 5.86), and source control as a protective factor (aOR 0.16). CONCLUSION: This study shows a concerning prevalence of CR in children with PA-BSIs, leading to high mortality. Inappropriate empiric treatment and sepsis were associated with mortality. The high prevalence of CR with an increased risk of inappropriate empiric treatment should be closely monitored.

Effect of Radiant Exposure on the Physical and Mechanical Properties of 10 Flowable and High-viscosity Bulk-fill Resin Composites.

OBJECTIVES: To evaluate the effect of the different radiant exposures from a multipeak light curing unit on the physical and mechanical properties of flowable and high-viscosity bulk-fill resin-based composites (RBC). METHODS: Five flowable bulk-fill RBCs (Tetric N-Flow Bulk-fill, Ivoclar Vivadent; Filtek Bulk Fill Flow, 3M Oral Care; Opus Bulk Fill Flow APS, FGM; Admira Fusion x-base, Voco and; and SDR Plus Bulk Fill Flowable, Dentsply Sirona) and five high-viscosity bulk-fill RBCs (Tetric N-Ceram Bulk-fill, Ivoclar Vivadent; Filtek One Bulk Fill, 3M Oral Care; Opus Bulk Fill APS, FGM; Admira Fusion x-tra, Voco; and SonicFill 2, Kerr) were photo-cured using a VALO Cordless light (Ultradent) for 10, 20, and 40 seconds at an irradiance of 1200, 800, or 400 mW/cm2, resulting in the delivery of 4, 8, 12, 16, 24, 32, or 48 J/cm2. Post-gel shrinkage (Shr) was calculated using strain-gauge test. The degree of conversion (DC, %) was calculated using FTIR. Knoop hardness (KH, N/mm2) and elastic modulus (E, MPa) were measured at the top and bottom surfaces. Logarithmic regressions between the radiant exposures and mechanical properties were calculated. Radiodensity was calculated using digital radiographs. Data of Shr and radiodensity were analyzed using two-way analysis of variance (ANOVA), and the DC, KH, and E data were analyzed with two-way ANOVA using split-plot repeated measurement tests followed by the Tukey test (a = 0.05). RESULTS: Delivering higher radiant exposures produced higher Shr values (p<0.001) and higher DC values (R2=0.808-0.922; R2=0.648-0.914, p<0.001), KH (R2=0.707-0.952; R2=0.738-0.919; p<0.001), and E (R2=0.501-0.925; R2=0.823-0.919; p<0.001) values for the flowable and high-viscosity RBCs respectively. Lower KH, E and Shr were observed for the flowable bulk-fill RBCs. All bulk-fill RBCs had a radiopacity level greater than the 4-mm thick aluminum step wedge. The radiant exposure did not affect the radiopacity. CONCLUSION: The Shr, DC, KH, and E values were highly correlated to the radiant exposure delivered to the RBCs. The combination of the higher irradiance for longer exposure time that resulted in radiant exposure between 24 J/cm2 to 48 J/cm2 produced better results than delivering 400 mW/cm2 for 40 s (16 J/cm2), and 800 mW/cm2 for 20 seconds (16 J/cm2) or 1200 mW/cm2 for 10 seconds (12 J/cm2). All the bulk-fill RBCs were sufficiently radiopaque compared to 4 mm of aluminum.

Estudio demográfico de las personas con nuevo diagnóstico de infección por VIH en el área sanitaria de un hospital de tercer nivel / Demographic study of persons living with HIV (PLWH) newly diagnosed in the healthcare area of a tertiary-level hospital

Introducción La lucha contra la infección por VIH sigue siendo un objetivo primordial del Sistema Nacional de Salud español. Los servicios de urgencias son un punto crítico a la hora disminuir las oportunidades de diagnóstico perdidas, donde se estima que se producen una de cada 3 oportunidades perdidas. El objetivo es examinar la distribución geográfica de los nuevos diagnósticos de VIH en el área de un hospital del centro de Madrid. Métodos Estudio descriptivo, observacional y retrospectivo que evalúa la distribución geográfica de los nuevos diagnósticos de VIH en el área asistencial de un hospital universitario de tercer nivel en la Comunidad de Madrid. Resultados Se analizaron 387 personas con un nuevo diagnóstico de infección por VIH entre los años 2018-2020, siendo en su mayoría personas jóvenes con una media de edad de 36±9 años. El 86% fueron hombres gais, bisexuales y otros hombres que tiene sexo con hombres y el 48,6% población inmigrante. El 15,3% se presentó con CD4+<200céls/mm3 y el 9,5% con una enfermedad definitoria de sida. El 32,7% y el 5,1% tenían un ARN-VIH-1>100.000 copias/mL y >500.000 copias/mL respectivamente, presentando, hasta un 13,7% de los sujetos mutaciones de resistencia al diagnóstico. En la distribución geográfica por las Áreas de Salud, el 51,4% de las personas procedían de 4 centros de salud y en 9 centros de salud se incluían más del 70% de los nuevos diagnosticados. Conclusión Conocer mejor la distribución geográfica de los nuevos diagnósticos de VIH por Áreas Sanitarias nos permite identificar las zonas de mayor riesgo de transmisión, para así poder dirigir y efectuar medidas de prevención, diagnóstico y tratamiento precoz (AU)

Introduction Countering HIV infection remains a primary objective of the Spanish National Health System. Emergency services play a crucial role in reducing missed diagnostic opportunities, with estimates suggesting that one in 3 such opportunities occur here. The aim of the study is to examine the geographical dispersion of newly diagnosed HIV cases, within a downtown Madrid hospital. Methods This is an observational, descriptive, retrospective study evaluating the geographical distribution of new HIV diagnoses in the care area of a tertiary University Hospital in the Community of Madrid. Results Three hundred and eighty-seven individuals with a new diagnosis of HIV infection between 2018 and 2020 were analysed, the majority being young people with an average age of 36±9 years. 86% were gay, bisexual and other men who have sex with men and 48.6% were immigrants. 15.3% presented with CD4+<200cells/mm3 and 9.5% with an AIDS-defining illness. 32.7% and 5.1% had an RNA-HIV-1>100,000copies/mL and >500,000copies/mL, respectively, with up to 13.7% of subjects presenting resistance mutations at diagnosis. Geographically, 51.4% of individuals came from 4 Health Centres and more than 70% of the new diagnoses were included in nine Health Centres. Conclusion Better understanding the geographical distribution of new HIV diagnoses by health areas allows us to identify areas of higher transmission risk, thereby directing and implementing prevention, early diagnosis, and treatment measures (AU)

Low rCBV values in glioblastoma tumor progression under chemoradiotherapy.

PURPOSE: After standard treatment for glioblastoma, perfusion MRI remains challenging for differentiating tumor progression from post-treatment changes. Our objectives were (1) to correlate rCBV values at diagnosis and at first tumor progression and (2) to analyze the relationship of rCBV values at tumor recurrence with enhancing volume, localization of tumor progression, and time elapsed since the end of radiotherapy in tumor recurrence. METHODS: Inclusion criteria were (1) age > 18 years, (2) histologically confirmed glioblastoma treated with STUPP regimen, and (3) tumor progression according to RANO criteria > 12 weeks after radiotherapy. Co-registration of segmented enhancing tumor VOIs with dynamic susceptibility contrast perfusion MRI was performed using Olea Sphere software. For tumor recurrence, we correlated rCBV values with enhancing tumor volume, with recurrence localization, and with time elapsed from the end of radiotherapy to progression. Analyses were performed with SPSS software. RESULTS: Sixty-four patients with glioblastoma were included in the study. Changes in rCBV values between diagnosis and first tumor progression were significant (p < 0.001), with a mean and median decreases of 32% and 46%, respectively. Mean rCBV values were also different (p < 0.01) when tumors progressed distally (radiation field rCBV values of 1.679 versus 3.409 distally). However, changes and, therefore, low rCBV values after radiotherapy in tumor recurrence were independent of time. CONCLUSION: Chemoradiation alters tumor perfusion and rCBV values may be decreased in the setting of tumor progression. Changes in rCBV values with respect to diagnosis, with low rCBV in tumor progression, are independent of time but related to the site of recurrence.

[Demographic study of persons living with HIV (PLWH) newly diagnosed in the healthcare area of a tertiary-level hospital]. / Estudio demográfico de las personas con nuevo diagnóstico de infección por VIH en el área sanitaria de un hospital de tercer nivel.

INTRODUCTION: Countering HIV infection remains a primary objective of the Spanish National Health System. Emergency services play a crucial role in reducing missed diagnostic opportunities, with estimates suggesting that one in 3 such opportunities occur here. The aim of the study is to examine the geographical dispersion of newly diagnosed HIV cases, within a downtown Madrid hospital. METHODS: This is an observational, descriptive, retrospective study evaluating the geographical distribution of new HIV diagnoses in the care area of a tertiary University Hospital in the Community of Madrid. RESULTS: Three hundred and eighty-seven individuals with a new diagnosis of HIV infection between 2018 and 2020 were analysed, the majority being young people with an average age of 36±9 years. 86% were gay, bisexual and other men who have sex with men and 48.6% were immigrants. 15.3% presented with CD4+<200cells/mm3 and 9.5% with an AIDS-defining illness. 32.7% and 5.1% had an RNA-HIV-1>100,000copies/mL and >500,000copies/mL, respectively, with up to 13.7% of subjects presenting resistance mutations at diagnosis. Geographically, 51.4% of individuals came from 4 Health Centres and more than 70% of the new diagnoses were included in nine Health Centres. CONCLUSION: Better understanding the geographical distribution of new HIV diagnoses by health areas allows us to identify areas of higher transmission risk, thereby directing and implementing prevention, early diagnosis, and treatment measures.

Study of the influence of nanoscale porosity on the microbial electroactivity between expanded graphite electrodes and Geobacter sulfurreducens biofilms.

Expanded graphite (EG) electrodes gather several advantages for their utilization in microbial electrochemical technologies (MET). Unfortunately, the low microbial electroactivity makes them non-practical for implementing them as electrodes. The objective of this work is to explore the enhancement of microbial electroactivity of expanded graphite (commercial PV15) through the generation of nanopores by CO2 treatment. The changes in properties were thoroughly analysed by TG, XRD, Raman, XPS, gas adsorption, SEM and AFM, as well as microbial electroactivity in the presence of Geobacter sulfurreducens. Nanopores remarkably enhance the microbially derived electrical current (60-fold increase). Given the inaccessibility of micron-sized bacteria to these nanopores, it is suggested that the electric charge exchanged by electroactive microorganisms might be greatly affected by the capability of the electrode to compensate these charges through ion adsorption. The increased microbial current density produced on activated PV15 opens the possibility of using such materials as promising electrodes in MET.

Evaluación del impacto, los patrones de tratamiento y las percepciones de pacientes y clínicos de los síntomas vasomotores moderado-graves asociados a la menopausia en España / Analysis of the impact, patterns of care, and perspectives of patients and physicians about moderate-to-severe menopausal vasomotor symptoms in Spain

Introducción: La menopausia puede originar distintos síntomas, siendo los vasomotores especialmente prevalentes y molestos. Este trabajo pretende conocer su impacto y los patrones/percepciones sobre el tratamiento en España, para lo que se han analizado las opiniones de clínicos y pacientes con síntomas vasomotores moderado-graves (SVM-MG). Métodos: Estudio transversal descriptivo de la subpoblación española del Programa de Enfermedades Específicas de Adelphi-VMS™. Médicos de atención primaria y de Ginecología y Obstetricia seleccionaron las pacientes. Estas fueron invitadas a rellenar una encuesta y los cuestionarios MENQOL y WPAI:SHP. Los datos se han presentado como porcentaje o media±desviación estándar. Resultados: Un total de 32 médicos de Atención Primaria y Ginecología y Obstetricia completaron los formularios de registro para 241 mujeres, de las cuales 143 experimentaban SVM-MG. A pesar del impacto global reportado en el trabajo (24,84%±17,49 presentismo) y en la calidad de vida (3,37±1,52 MENQOL), solo el 53,85% de las mujeres eran tratadas. El tratamiento hormonal de la menopausia era el más prescrito (77,92%), seguido de los inhibidores de la recaptación de serotonina (32,47%). El 59% de los clínicos estaba muy o completamente satisfecho con el tratamiento hormonal de la menopausia, mientras que solo el 19% lo estaba con los inhibidores de la recaptación de serotonina. Pacientes y especialistas indicaron un nivel de satisfacción inferior al 38% en el control de los SVM. Conclusiones: Los SVM-MG asociados a la menopausia tienen un importante impacto sobre la calidad de vida. Una mayor sensibilización en su manejo y mejores opciones terapéuticas contribuirían significativamente a mejorar la salud y bienestar de la mujer durante el climaterio.(AU)

Introduction: Menopause generates different symptoms, among which vasomotor symptoms are especially prevalent and bothersome. The aim of this work was to determine their impact and the treatment patterns and perceptions in Spain by analyzing the opinions of physicians and patients with moderate-to-severe vasomotor symptoms (MS-VMS). Methods: Descriptive cross-sectional study of the Spanish subpopulation from the Adelphi-VMS™ Disease-Specific Program. Primary Care and Gynecology and Obstetrics physicians selected the patients. These patients were invited to complete a survey and the MENQOL and WPAI:SHP questionnaires. Data are presented as percentage or mean±standard deviation. Results: Overall 32 Primary Care and Gynecology and Obstetrics physicians participated in the study, enrolling 241 women, of whom 143 experienced MS-VMS. Despite the reported impact on global work (24.84%±17.49 presentism) and quality of life (3.37±1.52 MENQOL score), only 53.85% of women with MS-VMS were treated. Menopausal hormone treatment was the most prescribed (77.92%), followed by serotonin reuptake inhibitors (32.47%). Fifty-nine percent of clinicians were very or completely satisfied with hormone treatment, whereas only 19% had this level of satisfaction with selective serotonin reuptake inhibitors. Less than 38% of patients and physicians were satisfied with the control of VMS. Conclusions: Menopause-associated MS-VMS have an important impact on quality of life. Increased awareness about their management and better therapeutic options would significantly contribute to improving women's health and well-being during their climacteric period.(AU)

Acute and subchronic effects of ibuprofen on the ten spotted live-bearer fish Cnesterodon decemmaculatus (Jenyns, 1842).

Ibuprofen (IBP) is an anti-inflammatory drug found in aquatic environments, potentially toxic for the biota. We exposed the test fish C. decemmaculatus to two environmentally relevant concentrations (50 and 100 µg IBP/L) for 4 and 12 d and evaluated the effect on some biomarkers. Micronucleus test, nuclear abnormality test and comet assay indicated cyto-genotoxicity at both concentrations and exposure periods. Oxidative stress and biochemical biomarkers were not affected, excepting muscle AChE activity for 4 d. Muscle metabolic biomarkers showed significant decrease in ETS, lipid and protein content, while carbohydrate content was not affected. The CEA index increased at the lower IBP concentration for 4 and 12 d, possibly due to changes in body energy reserves. A full-factorial GLM performed to assess the effects of IBP and exposure times showed that the metabolic and genotoxicity biomarkers were the most sensitive to IBP toxicity, mainly at 50 µg IBP/L for 4 d.

Effect of the Absence of HEMA on the Bonding Properties of Universal Adhesive Systems Containing 10-MDP: An In Vitro Study.

OBJECTIVES: To evaluate the absence of 2-hydroxyethyl methacrylate (HEMA) on the adhesive properties with enamel and dentin of universal adhesive systems containing 10-methacryloyloxydecyl dihydrogen phosphate (MDP). METHODS AND MATERIALS: One hundred and twelve caries-free third molars were used to test adhesion to dentin (n=64) and enamel (n=48). For each substrate, teeth were divided into eight experimental groups: four different adhesives each using two adhesive strategies. The adhesives used were: (1) Scotchbond Universal (SBU, 3M Oral Care, St Paul, MN, USA) as a HEMA-containing universal adhesive; (2) Gluma Bond Universal (GBU, Kulzer, Hanau, Germany); (3) Solare Universal Bond (SUB, GC, Tokyo, Japan); and (4) Zipbond Universal (ZIP, SDI, Victoria, Australia) as HEMA-free universal adhesives. The adhesive strategies used were etch-and-rinse (ER) and self-etch (SE). For dentin tests, the occlusal third of the crown of all teeth was removed and an adhesive protocol was applied. After completing the restoration, specimens were sectioned into bonded sticks (0.8 mm 2) and tested for microtensile bond strength (µTBS), in situ degree of conversion (DC), and nanoleakage (NL) by scanning electron microscopy. For enamel tests, teeth were sectioned into four parts (buccal, lingual, and proximal), and an adhesive protocol was applied. After completing the restoration, the specimens were tested for their microshear bond strength (µSBS). For in situ degree of conversion (DC) and nanoleakage (NL) evaluation of enamel, the specimens were sectioned in slices to be evaluated. The data for each substrate were subjected to two-way ANOVA and Tukey's test (α=0.05) for each property evaluated. RESULTS: The SBU and ZIP adhesives showed the highest µSBS, and DC (dentin and enamel) and lower NL (dentin) values compared to GBU and SUB (p=0.001). However, SBU showed better results in terms of µTBS and µSBS (SE strategy), and DC (dentin and enamel) than ZIP. Strategy ER presented higher values of µTBS and µSBS when compared to strategy SE (p=0.001), except for SBU. CONCLUSION: The effect of the absence of HEMA in commercial universal adhesive systems on enamel and dentin adhesive properties appears to be material-dependent.

The neurobiology of insulin-like growth factor I: From neuroprotection to modulation of brain states.

After decades of research in the neurobiology of IGF-I, its role as a prototypical neurotrophic factor is undisputed. However, many of its actions in the adult brain indicate that this growth factor is not only involved in brain development or in the response to injury. Following a three-layer assessment of its role in the central nervous system, we consider that at the cellular level, IGF-I is indeed a bona fide neurotrophic factor, modulating along ontogeny the generation and function of all the major types of brain cells, contributing to sculpt brain architecture and adaptive responses to damage. At the circuit level, IGF-I modulates neuronal excitability and synaptic plasticity at multiple sites, whereas at the system level, IGF-I intervenes in energy allocation, proteostasis, circadian cycles, mood, and cognition. Local and peripheral sources of brain IGF-I input contribute to a spatially restricted, compartmentalized, and timed modulation of brain activity. To better define these variety of actions, we consider IGF-I a modulator of brain states. This definition aims to reconcile all aspects of IGF-I neurobiology, and may provide a new conceptual framework in the design of future research on the actions of this multitasking neuromodulator in the brain.

Beyond hyperglycemia: glycaemic variability as a prognostic factor after acute ischemic stroke.

INTRODUCTION: Glycaemic variability (GV) refers to variations in blood glucose levels, and may affect stroke outcomes. This study aims to assess the effect of GV on acute ischaemic stroke progression. METHODS: We performed an exploratory analysis of the multicentre, prospective, observational GLIAS-II study. Capillary glucose levels were measured every 4 hours during the first 48 hours after stroke, and GV was defined as the standard deviation of the mean glucose values. The primary outcomes were mortality and death or dependency at 3 months. Secondary outcomes were in-hospital complications, stroke recurrence, and the impact of the route of insulin administration on GV. RESULTS: A total of 213 patients were included. Higher GV values were observed in patients who died (n = 16; 7.8%; 30.9 mg/dL vs 23.3 mg/dL; p = 0.05). In a logistic regression analysis adjusted for age and comorbidity, both GV (OR = 1.03; 95% CI, 1.003-1.06; p = 0.03) and stroke severity (OR = 1.12; 95% CI, 1.04-1.2; p = 0.004) were independently associated with mortality at 3 months. No association was found between GV and the other outcomes. Patients receiving subcutaneous insulin showed higher GV than those treated with intravenous insulin (38.95 mg/dL vs 21.34 mg/dL; p < 0.001). CONCLUSIONS: High GV values during the first 48 hours after ischaemic stroke were independently associated with mortality. Subcutaneous insulin may be associated with higher VG levels than intravenous administration.

Más allá de la hiperglucemia: la variabilidad glucémica como factor pronóstico en el infarto cerebral agudo / Beyond hyperglycemia: glycaemic variability as a prognostic factor after acute ischemic stroke

Introducción: La variabilidad glucémica (VG) hace referencia a las oscilaciones en los niveles de glucosa en sangre y podría influir en el pronóstico del ictus. Objetivo: Analizar el efecto de la VG en la evolución del infarto cerebral agudo (IC).MétodosAnálisis exploratorio del estudio GLIAS-II (multicéntrico, prospectivo y observacional). Se midieron los niveles de glucemia capilar cada cuatro horas durante las primeras 48 horas y la VG se definió como la desviación estándar de los valores medios. Variables principales: mortalidad y muerte o dependencia a los tres meses. Variables secundarias: porcentaje de complicaciones intrahospitalarias y de recurrencia de ictus, e influencia de la vía de administración de insulina sobre la VG.ResultadosSe incluyeron 213 pacientes. Los pacientes que fallecieron (N = 16;7,8%) presentaron mayores valores de VG (30,9 mg/dL vs. 23,3 mg/dL; p = 0,05). En el análisis de regresión logística ajustado por edad y comorbilidad, tanto la VG (OR = 1,03; IC del 95%: 1,003-1,06: p = 0,03) como la gravedad del IC (OR = 1,12; IC del 95%: 1,04-1,2; p = 0,004) se asociaron de forma independiente con la mortalidad a los tres meses. No se encontró asociación entre la VG y las demás variables de estudio. Los pacientes que recibieron tratamiento con insulina subcutánea mostraron una mayor VG que los tratados con insulina intravenosa (38,9 mg/dL vs. 21,3 mg/dL; p < 0,001).ConclusionesValores elevados de VG durante las primeras 48 horas tras el IC se asociaron de forma independiente con la mortalidad. La administración subcutánea de insulina podría condicionar una mayor VG que la vía intravenosa. (AU)

Introduction: Glycaemic variability (GV) refers to variations in blood glucose levels, and may affect stroke outcomes. This study aims to assess the effect of GV on acute ischaemic stroke progression.MethodsWe performed an exploratory analysis of the multicentre, prospective, observational GLIAS-II study. Capillary glucose levels were measured every 4 hours during the first 48 hours after stroke, and GV was defined as the standard deviation of the mean glucose values. The primary outcomes were mortality and death or dependency at 3 months. Secondary outcomes were in-hospital complications, stroke recurrence, and the impact of the route of insulin administration on GV.ResultsA total of 213 patients were included. Higher GV values were observed in patients who died (n = 16; 7.8%; 30.9 mg/dL vs 23.3 mg/dL; p = 0.05). In a logistic regression analysis adjusted for age and comorbidity, both GV (OR = 1.03; 95% CI, 1.003-1.06; p = 0.03) and stroke severity (OR = 1.12; 95% CI, 1.04-1.2; p = 0.004) were independently associated with mortality at 3 months. No association was found between GV and the other outcomes. Patients receiving subcutaneous insulin showed higher GV than those treated with intravenous insulin (38.95 mg/dL vs 21.34 mg/dL; p < 0.001).ConclusionsHigh GV values during the first 48 hours after ischaemic stroke were independently associated with mortality. Subcutaneous insulin may be associated with higher VG levels than intravenous administration. (AU)

Hypoxia and Wnt signaling inversely regulate expression of chondroprotective molecule ANP32A in articular cartilage.

OBJECTIVES: ANP32A is a key protector of cartilage health, via preventing oxidative stress and Wnt hyper-activation. We aimed to unravel how ANP32A is regulated in cartilage. METHODS: A bioinformatics pipeline was applied to identify regulators of ANP32A. Pathways of interest were targeted to study their impact on ANP32A in in vitro cultures of the human chondrocyte C28/I2 cell-line and primary human articular chondrocytes (hACs) from up to five different donors, using Wnt-activator CHIR99021, hypoxia-mimetic IOX2 and a hypoxia chamber. ANP32A was evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. In vivo, the effect of hypoxia was examined by immunohistochemistry in mice injected intra-articularly with IOX2 after destabilization of the medial meniscus. Effects of Wnt hyper-activation were investigated using Frzb-knockout mice and wild-type mice treated intra-articularly with CHIR99021. Wnt inhibition effects were assessed upon intra-articular injection of XAV939. RESULTS: The hypoxia and Wnt signaling pathways were identified as networks controlling ANP32A expression. In vitro and in vivo experiments demonstrated increases in ANP32A upon hypoxic conditions (1.3-fold in hypoxia in C28/I2 cells with 95% confidence interval (CI) [1.11-1.54] and 1.90-fold in hACs [95% CI: 1.56-2] and 1.67-fold in ANP32A protein levels after DMM surgery with IOX2 injections [95% CI: 1.33-2.08]). Wnt hyper-activation decreased ANP32A in chondrocytes in vitro (1.23-fold decrease [95% CI: 1.02-1.49]) and in mice (1.45-fold decrease after CHIR99021 injection [95% CI: 1.22-1.72] and 1.41-fold decrease in Frzb-knockout mice [95% CI: 1.00-1.96]). Hypoxia and Wnt modulated ataxia-telangiectasia mutated serine/threonine kinase (ATM), an ANP32A target gene, in hACs (1.89-fold increase [95% CI: 1.38-2.60] and 1.41-fold decrease [95% CI: 1.02-1.96]). CONCLUSIONS: Maintaining hypoxia and limiting Wnt activation sustain ANP32A and protect against osteoarthritis.

Hemorragia intracerebral fatal asociada al síndrome de trombosis con trombocitopenia tras la vacuna ChAdOx1-S / Fatal intracerebral haemorrhage associated with thrombosis with thrombocytopenia syndrome after ChAdOx1-S vaccine

Introducción: La pandemia por COVID-19 ha tenido un impacto devastador en la salud, la sociedad y la economía en el mundo. Por ello, las vacunas contra el coronavirus del síndrome respiratorio agudo grave 2 (SARS-CoV-2) han surgido como medida importante para combatir la pandemia. ChAdOx1-S (Oxford-AstraZeneca) es una vacuna vectorizada por adenovirus que expresa la proteína de espiga del SARS-CoV-2. Se han notificado varios casos de trombosis y trombocitopenia inusuales tras la ChAdOx1-S que imitan la trombocitopenia autoinmune inducida por heparina. Esta situación se denomina síndrome de trombosis con trombocitopenia (STT), y se han descrito casos de hemorragia intracerebral secundaria. Caso clínico: Presentamos un caso de hemorragia intracerebral tras la vacunación con ChAdOx1-S. Una paciente de mediana edad sin antecedentes médicos de interés fue atendida en urgencias 16 días después de la primera dosis de ChAdOx1-S con una hemiplejía izquierda de inicio repentino y una cefalea opresiva holocraneal grave. No recibió heparina los 100 días anteriores. El análisis de sangre mostró trombocitopenia moderada y en la tomografía computarizada se observó una hemorragia lobar frontal derecha sin trombosis en la venografía por tomografía computarizada. Se confirmó la presencia de anticuerpos contra el factor 4 de las plaquetas en la sangre. La paciente presentó un síndrome de hipertensión intracraneal resistente al tratamiento y falleció tres semanas después. Conclusiones: El STT es un efecto adverso infrecuente de la vacuna ChAdOx1-S que se define por la presencia de trombosis en localizaciones infrecuentes. En nuestro caso, describimos una hemorragia intracerebral espontánea secundaria a la trombocitopenia desencadenada por el STT. Representa una presentación clínica poco frecuente del STT.(AU)

INTRODUCTION: The COVID-19 pandemic has had a devastating impact on health, society and economics worldwide. Therefore, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have recently emerged as an important measure to fight the pandemic. ChAdOx1-S (Oxford-AstraZeneca) is an adenovirus-vectored vaccine that expresses the SARS-CoV-2 spike protein. It shows an acceptable safety profile. Nevertheless, several cases of unusual thrombosis and thrombocytopenia have been reported after initial vaccination with ChAdOx1-S mimicking autoimmune heparin-induced thrombocytopenia. This condition has been called thrombosis with thrombocytopenia syndrome (TTS) and complications such as intracerebral haemorrhage have been described. CASE REPORT: We present a case of intracerebral haemorrhage after ChAdOx1-S vaccination. Middle-aged patient with no prior medical history was seen in the emergency room 16 days after the first dose of ChAdOx1-S vaccine with sudden onset left hemiplegia and severe holocranial oppressive headache. She did not receive heparin treatment in the previous 100 days. Blood test showed moderate thrombocytopenia and a right frontal lobar haemorrhage was seen on computed tomography scan, computed tomography venography was negative for thrombosis. The presence of antibodies against platelet factor 4 was confirmed. The patient’s neurological condition progressively worsened. She developed a treatment resistant intracranial hypertension syndrome and she died three weeks later. CONCLUSIONS: TTS is a rare adverse effect of ChAdOx1-S vaccine, defined by the presence of thrombosis in uncommon locations. In our case we report an spontaneous intracerebral haemorrhage probable due to the thrombocytopenia related to probable TTS. It represents a rare clinical presentation of TTS.(AU)

Fatal intracerebral haemorrhage associated with thrombosis with thrombocytopenia syndrome after ChAdOx1-S vaccine. / Hemorragia intracerebral fatal asociada al síndrome de trombosis con trombocitopenia tras la vacuna ChAdOx1-S.

INTRODUCTION: The COVID-19 pandemic has had a devastating impact on health, society and economics worldwide. Therefore, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have recently emerged as an important measure to fight the pandemic. ChAdOx1-S (Oxford-AstraZeneca) is an adenovirus-vectored vaccine that expresses the SARS-CoV-2 spike protein. It shows an acceptable safety profile. Nevertheless, several cases of unusual thrombosis and thrombocytopenia have been reported after initial vaccination with ChAdOx1-S mimicking autoimmune heparin-induced thrombocytopenia. This condition has been called thrombosis with thrombocytopenia syndrome (TTS) and complications such as intracerebral haemorrhage have been described. CASE REPORT: We present a case of intracerebral haemorrhage after ChAdOx1-S vaccination. Middle-aged patient with no prior medical history was seen in the emergency room 16 days after the first dose of ChAdOx1-S vaccine with sudden onset left hemiplegia and severe holocranial oppressive headache. She did not receive heparin treatment in the previous 100 days. Blood test showed moderate thrombocytopenia and a right frontal lobar haemorrhage was seen on computed tomography scan, computed tomography venography was negative for thrombosis. The presence of antibodies against platelet factor 4 was confirmed. The patient's neurological condition progressively worsened. She developed a treatment resistant intracranial hypertension syndrome and she died three weeks later. CONCLUSIONS: TTS is a rare adverse effect of ChAdOx1-S vaccine, defined by the presence of thrombosis in uncommon locations. In our case we report an spontaneous intracerebral haemorrhage probable due to the thrombocytopenia related to probable TTS. It represents a rare clinical presentation of TTS.

TITLE: Hemorragia intracerebral fatal asociada al síndrome de trombosis con trombocitopenia tras la vacuna ChAdOx1-S.Introducción. La pandemia por COVID-19 ha tenido un impacto devastador en la salud, la sociedad y la economía en el mundo. Por ello, las vacunas contra el coronavirus del síndrome respiratorio agudo grave 2 (SARS-CoV-2) han surgido como medida importante para combatir la pandemia. ChAdOx1-S (Oxford-AstraZeneca) es una vacuna vectorizada por adenovirus que expresa la proteína de espiga del SARS-CoV-2. Se han notificado varios casos de trombosis y trombocitopenia inusuales tras la ChAdOx1-S que imitan la trombocitopenia autoinmune inducida por heparina. Esta situación se denomina síndrome de trombosis con trombocitopenia (STT), y se han descrito casos de hemorragia intracerebral secundaria. Caso clínico. Presentamos un caso de hemorragia intracerebral tras la vacunación con ChAdOx1-S. Una paciente de mediana edad sin antecedentes médicos de interés fue atendida en urgencias 16 días después de la primera dosis de ChAdOx1-S con una hemiplejía izquierda de inicio repentino y una cefalea opresiva holocraneal grave. No recibió heparina los 100 días anteriores. El análisis de sangre mostró trombocitopenia moderada y en la tomografía computarizada se observó una hemorragia lobar frontal derecha sin trombosis en la venografía por tomografía computarizada. Se confirmó la presencia de anticuerpos contra el factor 4 de las plaquetas en la sangre. La paciente presentó un síndrome de hipertensión intracraneal resistente al tratamiento y falleció tres semanas después. Conclusiones. El STT es un efecto adverso infrecuente de la vacuna ChAdOx1-S que se define por la presencia de trombosis en localizaciones infrecuentes. En nuestro caso, describimos una hemorragia intracerebral espontánea secundaria a la trombocitopenia desencadenada por el STT. Representa una presentación clínica poco frecuente del STT.

Endarterectomy, Stenting, or Medical Treatment for Symptomatic Carotid Near-Occlusion: Results from CAOS, a Multicenter Registry Study.

BACKGROUND AND PURPOSE: The treatment of symptomatic carotid near-occlusion is controversial. Our aim was to analyze the results of carotid endarterectomy and carotid artery stent placement in patients with symptomatic carotid near-occlusion and to identify factors related to technical failure, periprocedural complications, and restenosis. MATERIALS AND METHODS: We conducted a multicenter, prospective nonrandomized study. Patients with angiography-confirmed carotid near-occlusion were included. We assessed the revascularization rate and periprocedural stroke or death. Twenty-four-month clinical and carotid imaging follow-up was performed, and rates of carotid restenosis or occlusion, ipsilateral stroke, and mortality were analyzed. Carotid artery stent placement, carotid endarterectomy, and medical treatment were compared. RESULTS: One hundred forty-one patients were included. Forty-four carotid artery stent placement and 23 carotid endarterectomy procedures were performed within 6 months after the event. Complete revascularization was achieved in 83.6%, 81.8% in the carotid artery stent placement group and 87% with carotid endarterectomy (P = .360). Periprocedural stroke or death occurred in 6% (carotid artery stent placement = 2.3%; carotid endarterectomy = 13%; P = .077) and was not related to revascularization failure. The carotid restenosis or occlusion rate was 8.3% (5% restenosis, 3.3% occlusion); with carotid artery stent placement it was 10.5%; and with carotid endarterectomy it was 4.5% (P = .419). The 24-month cumulative rate of ipsilateral stroke was 4.8% in the carotid artery stent placement group, 17.4% for carotid endarterectomy, and 13.1% for medical treatment (P = .223). Mortality was 12%, 4.5%, and 5.6%, respectively (P = .422). Revascularization failure and restenosis occurred more frequently in patients with full collapse compared with patients without full collapse (33.3% versus 5.6%, P = .009; 21.4% versus 2.9%, P = .032, respectively). CONCLUSIONS: Carotid artery stent placement and carotid endarterectomy are associated with high rates of failure and periprocedural stroke. Carotid near-occlusion with full collapse appears to be associated with an increased risk of technical failure and restenosis. Carotid near-occlusion revascularization does not seem to reduce the risk of stroke at follow-up compared with medical treatment.

Influence of Irradiance and Exposure Times on the Mechanical and Adhesive Properties of Universal Adhesives with Dentin.

OBJECTIVES: This study evaluated the influence of irradiance/exposure time on the Knoop hardness (KHN) and polymer cross-linking density (PCLD), as well as microtensile bond strength (µTBS), nanoleakage (NL), and in situ degree of conversion (DC) of universal adhesives. METHODS AND MATERIALS: Two universal adhesive systems, Clearfil Universal Bond Quick (CUQ) and Scotchbond Universal Adhesive (SBU), were light-cured using various irradiance/exposure times: 1400 mW/cm2 for 5 s (1400*5); 1400 mW/cm2 for 10 s (1400*10); 3200 mW/cm2 for 5 s (3200*5); and 3200 mW/cm2 for 10 s (3200*10). Adhesive disks from each group were used to measure PCLD by KHN. One hundred and twenty-eight human molars were randomly assigned to 16 groups according to the following variables: adhesive system vs adhesive strategies vs radiance/exposure times. After restoration, specimens were sectioned into resin-dentin sticks and tested for µTBS, NL, and DC. The data from PCLD (%), KHN, µTBS (MPa), NL (%), and DC (%) data were subjected to ANOVA and Tukey's test (α=0.05). RESULTS: Significant reductions in KHN, µTBS, and DC (p=0.00001) values and an increase in NL and PCLD (p=0.00001) values were observed for 3200*10 when compared with other groups. Higher KHN, µTBS, and DC (p=0.000001) values were observed for 3200*5 in comparison with the other groups. The 1400*5 (7 J/cm2) and 1400*10 (14 J/cm2) groups showed intermediate values (p=0.000001). CONCLUSION: Although similar results in terms of hardness, polymer cross-linking density and nanoleakage were observed when 5 seconds at 3200 mW/cm2 and 10 seconds at 1400 mW/cm2 groups were compared, the use of higher irradiance (3200 mW/cm2) for only 5 seconds showed better results in terms of bond strength and degree of conversion for both universal adhesives to dentin. The prolonged exposure time (10 seconds) at the higher irradiance (3200 mW/cm2) showed the worst results.