Prediction of vascular events in subjects with subclinical atherosclerosis and the metabolic syndrome: the role of markers of inflammation.

AIM: The presence of the metabolic syndrome (MS) increases cardiovascular morbidity and mortality and we aimed to assess the outcome in subjects with the MS and subclinical atherosclerosis. METHODS: We followed-up for five years 339 Mediterranean subjects with asymptomatic carotid intima-media thickness >0.9 mm (men: 60%; age: 66±5 years), of whom 130 had the MS (men: 59%; age: 66±5 years), evaluating at baseline traditional cardiovascular risk factors (including male gender, older age, obesity, hypertension, diabetes, smoking, family history of cardiovascular diseases, dyslipidemia) and plasma levels of C-reactive protein and fibrinogen. RESULTS: Cardio- and cerebrovascular events were registered in the 29% of subjects with the MS and in the 20% of those without it and the presence of more criteria for the diagnosis of the MS was significantly associated with vascular morbidity and mortality. By multivariate analysis, including all baseline variables, independent predictive roles for the events were found for elevated markers of inflammation (OR 3.8), elevated fasting glucose (OR 2.1) and elevated triglycerides (OR 1.4). CONCLUSION: These findings confirm a worst vascular outcome in subjects with more criteria for the diagnosis of the MS and further suggest the need of future research to understand the combined role of inflammation and the MS in the progression from subclinical to clinical atherosclerosis

Preliminary Assessment of Two Simultaneous and Proportional Myocontrol Methods for 3-DoFs Prostheses Using Incremental Learning

Despite progressive developments over the last decades, current upper limb prostheses still lack a suitable control able to fully restore the functionalities of the lost arm. Traditional control approaches for prostheses fail when simultaneously actuating multiple Degrees of Freedom (DoFs), thus limiting their usability in daily-life scenarios. Machine learning, on the one hand, offers a solution to this issue through a promising approach for decoding user intentions but fails when input signals change. Incremental learning, on the other hand, reduces sources of error by quickly updating the model on new data rather than training the control model from scratch. In this study, we present an initial evaluation of a position and a velocity control strategy for simultaneous and proportional control over 3-DoFs based on incremental learning. The proposed controls are tested using a virtual Hannes prosthesis on two healthy participants. The performances are evaluated over eight sessions by performing the Target Achievement Control test and administering SUS and NASA-TLX questionnaires. Overall, this preliminary study demonstrates that both control strategies are promising approaches for prosthetic control, offering the potential to improve the usability of prostheses for individuals with limb loss. Further research extended to a wider population of both healthy subjects and amputees will be essential to thoroughly assess these control paradigms

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell

Pensar la infancia I

La Maestría en Infancia de la Universidad Tecnológica de Pereira-Colombia, se complace en entregar al público interesado el primer volumen de su serie “Pensar la infancia”. El cual reúne los aportes de profesores nacionales e internacionales y egresados de las dos primeras promociones del programa. La figura del “calidoscopio” nos sirve para exponer la variedad de “temas, imágenes y representaciones” de la infancia que caracteriza a esta publicación. Solo hasta hace poco tiempo (década del ochenta del siglo pasado), la infancia mereció la atención de la sociología, desde entonces, y de manera paulatina, ella se convierte en un objeto de investigación independiente. Este desplazamiento se interesa por un objeto y sujeto social, cuya imagen es a la vez objeto de fascinación y de controversias: la infancia. Imagen que oscila entre numerosas contradicciones, particularmente visibles en los títulos de gran cantidad de publicaciones: niño rey, niño víctima, y con frecuencia, niño problema, entre otros.PRESENTACIÓN ....................................................................................... 13 PARTE I INFANCIAS ...................................................................................... 21 1. Paulo Freire: Otras infancias para la infancia Walter Omar Kohan..................................................................................................23 2. Pensamiento pedagógico en Agustín Nieto Caballero: la infancia moderna y la irrupción de la Escuela Activa en Colombia Absalón Jiménez Becerra ....................................................................................... 69 3. Literatura e infancia: las niñas y los niños como actores sociales Diana Alexandra Jiménez Perea y Natalia Ximena Castrillón García ............ 109 4. Philippe Ariès: nacimiento, posteridad y vigencia de un modelo de interpretación de la infancia. Una revisión de la literatura historiográfica francófona Miguel Ángel Gómez Mendoza ........................................................................... 127 5. Concepciones de infancia en la posmodernidad Sandra Liliana Osorio Rodríguez ........................................................................ 143 6. Sociología de la infancia: surgimiento de un campo de estudio, evolución y perspectivas María Victoria Alzate Piedrahíta ......................................................................... 167 7. El carácter material de la infancia perspectivas teóricas para el estudio del consumo infantil Diana Marcela Aristizábal García......................................................................... 181 PARTE II EXPERIENCIAS DE INFANCIA Y EDUCACIÓN ........................ 217 8. Desarrollo del pensamiento filosófico en el marco de un proyecto bilingüe en la Primera Infancia Paola Andrea Hincapié Rincón y Diana Carolina Durango Isaza ................... 221 9. Pensar las infancias desde el Bicentenario Slendi Paola Valbuena Velandia............................................................................ 289 10. Infancia en el Bicentenario: una reflexión desde la práctica docente Misael Andrés Moreno Buitrago .......................................................................... 317 11. Pedagogía hospitalaria, infancia y educación Yenny Alejandra Ramírez García y Maritza Arango Puerta............................. 343 12. Representaciones sociales de la infancia desde la perspectiva de los niños y las niñas Leonardo Fabio Gómez Ramírez y Leydi Marcela Rivera Noreña................... 381 13. La participación de la infancia: un camino al reconocimiento de la ciudadanía Elizabeth Martínez ............................................................................................... 415 14. El coraje de ser auténticos. Análisis de la categoría familia en tres relatos de vida de jóvenes con experiencia de vida en calle en su infancia Humberto Gómez Duque y Benicio Enrique Montes Posada.......................... 431 15. Cultura infantil Embera Chamí Daniela Benavides Rosero y Milton Andrés Valencia Forero........................... 469 CONTENIDO PARTE III TRADUCCIONES: INFANCIA, HISTORIA Y SOCIOLOGÍA ... 505 16. La infancia como forma estructural Jans Qvortrup ........................................................................................................ 507 17. Agencia Allison James ......................................................................................................... 535 18. La infancia: una mirada desde las ciencias sociales Régine Sirota ......................................................................................................... 559 19. ¿Historia de la infancia, historia sin palabras? Egle Becchi y Dominique Julia ............................................................................ 597 20. Tomando en serio un rito de la infancia: el aniversario Régine Sirota .......................................................................................................... 641 PARTE IV RESEÑAS ....................................................................................... 653 21. Historia de la infancia: a propósito de la obra de Egle Becchi y Dominique Julia Miguel Ángel Gómez Mendoza............................................................................ 65

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

A prenylated dsRNA sensor protects against severe COVID-19

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response