p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes

It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes

A transcriptional complex of NGATHA and bHLH transcription factors directs stigma development in Arabidopsis

[EN] The stigma is an angiosperm-specific tissue that is essential for pollination. In the last two decades, several transcription factors with key roles in stigma development in Arabidopsis thaliana have been identified. However, genetic analyses have thus far been unable to unravel the precise regulatory interactions among these transcription factors or the molecular basis for their selective roles in different spatial and temporal domains. Here, we show that the NGATHA (NGA) and HECATE (HEC) transcription factors, which are involved in different developmental processes but are both essential for stigma development, require each other to perform this function. This relationship is likely mediated by their physical interaction in the apical gynoecium. NGA/HEC transcription factors subsequently upregulate INDEHISCENT (IND) and SPATULA and are indispensable for the binding of IND to some of its targets to allow stigma differentiation. Our findings support a nonhierarchical regulatory scenario in which the combinatorial action of different transcription factors provides exquisite temporal and spatial specificity of their developmental outputs.This work was supported by the Spanish Ministerio de Economia y Competitividad (grant BIO2015-64531-R to C.F.) and the Spanish Ministerio de Ciencia, Innovacion y Universidades (grant RTI2018-099239-B-I00 to C.F.).Ballester Fuentes, P.; Martinez-Godoy, MA.; Ezquerro, M.; Navarrete-Gomez, M.; Trigueros González, M.; Rodriguez Concepcion, M.; Ferrandiz Maestre, C. (2021). A transcriptional complex of NGATHA and bHLH transcription factors directs stigma development in Arabidopsis. The Plant Cell. 33(12):3645-3657. https://doi.org/10.1093/plcell/koab236S36453657331

A Preliminary Randomized Clinical Trial on the Effect of Cervicothoracic Manipulation Plus Supervised Exercises vs a Home Exercise Program for the Treatment of Shoulder Impingement

Objective: The purpose of this study was to investigate changes in pain, disability, and range of movement after cervicothoracic manipulation plus exercise therapy in individuals with unilateral shoulder impingement syndrome.Methods: Forty-one patients (30 men, 11 women; aged 47 +/- 9) diagnosed with unilateral shoulder impingement syndrome attended 10 sessions for 5 weeks (2 sessions/wk). Eligible patients were randomly allocated to 2 study groups: cervicothoracic manipulation plus exercise therapy (n = 21) or home exercise program (n = 20). The outcomes measures included the visual analog scale (VAS); the Disabilities of the Arm, Shoulder, and Hand score; Shoulder Disability Questionnaire; subacromial impingement syndrome (Hawkins-Kennedy Test and Neer Test); and shoulder active range of motion (movements of flexion, extension, rotation, adduction, and abduction). Assessments were applied at baseline and 24 hours after completing 5 weeks of related interventions.Results: After 5 weeks of treatment significant between-group differences were observed in the Disabilities of the Arm, Shoulder, and Hand score (P = .012); however, no statistically significant differences were achieved for Shoulder Disability Questionnaire (P = .061) and pain intensity (P = .859). Both groups improved with regard to disability and clinical tests for detecting subacromial impingement syndrome.Conclusions: This clinical trial suggests that cervicothoracic manipulative treatment with mobilization plus exercise therapy may improve intensity of pain and range of motion compared with the home exercise group alone; the home exercise group had significant changes for flexion, extension, adduction, and abduction, but not for external and internal rotation movement in patients with shoulder impingement

Durabilidad de la respuesta inmune antihepatitis B en trabajadores de la salud peruanos con 6 años de vacunados

Partiendo de la importancia que la Organización Mundial de la Salud y el Centro para el Control de las Enfermedades le atribuyen a la protección de los trabajadores de la salud contra la hepattis viral tipo B (VHB), en 1993 el Instituto Peruano del Seguro Social (hoy ESSALUD), orientó la vacunación del personal de riesgo en los 4 hospitales nacionales, mediante la vacuna cubana Heberbiovac HB (20 mg, esquema 0-1-2 meses). El propósito fue evaluar la persistencia de los anticuerpos en los vacunados después de 6 años de la inmunización y la posible existencia de marcadores de infección por el virus B. Se estudiaron los sueros de 144 trabajadores de la salud, para una cobertura de 70,24 % en relación con los seroprotegidos en el estudio inicial. Para la detección de los marcadores en el suero se emplearon métodos inmunoenzimáticos comerciales. El AgsHB y el anti-AgcHB fueron negativos en todas las muestras serológicas, por lo que se afirmó que en ninguno de los vacunados hubo evidencias de infección por este virus. El anti-AgsHB fue positivo, todos presentaban seroconversión, con seroprotección e hiperrespuesta de 91,6 y 43,7 %, respectivamente. El tiempo de vida media del anti-AgsHB (t ½) es de 3 años, se pronosticó que los niveles de anticuerpos serían superiores a 10 UI/L hasta después de 15 años de finalizado el esquema. Los menores de 40 años tuvieron niveles de seroprotección e hiperrespuesta significativamente mayores; las mujeres se mantuvieron en categorías de respuesta superiores. Se recomendó evaluar la memoria pos-refuerzo en los casos de seroconversión, no seroprotegidos, y extender el trabajo con ESSALUD a otros hospitales del paísOn the basis of the importance given by the Health World Organization and the Disease Control Center to the protection of health workers against viral hepatitis B(HBV), the Peruvian Institute of Social Security(presently ESSALUD) instructed in 1993 the vaccination of health personnel at risk in 4 national hospitals by using the Cuban vaccine called Herberbiovac HB(20 mg, 0,1,and 2 month schedule). The purpose was to evaluate the persistence of antibodies in the immunized workers six years after the immunization program and the possible presence of HB virus infection markers. Sera from 144 health workers were studied covering 70.24% of seroprotected subjects in comparison with seroprotected subjects in the initial study. Conventional immunoenzymatic methods were used to detect markers in the serum, HbsAg and antibodies to HbcAg were negative in all the serological samples, an outcome that showed that any of the vaccinated persons had traces of HB virus infection. The anti-HbsAg was positive, seroconversion was 100% whereas seroprotection and hyperesponse amounted to 91.6 and 43.7% respectively. The mean lifetime of anti-HbsAg is 3 years but it was predicted that the levels of antibodies would reach over 10 UI/L after 15 years of the vaccination schedule completion. Subjects aged under 40 years had significantly higher levels of seroprotection and hyperesponse, being females those in the higher response categories. The evaluation of the post-vaccination reinforcement immunological response in seroconverted non-seroprotected cases and the extension of the work with ESSALUD to other hospitals in the country were recommende

Atenciones debidas a patología reumatológica en el Servicio de Emergencias del Instituto Nacional de Salud del Niño (Lima, Perú) durante el periodo Enero 2012-Junio 2014

Objetivos: Evaluar las causas más frecuentes de atenciones por patología reumatológica en el servicio de emergencias de un hospital pediátrico peruano de tercer nivel.Pacientes y Métodos: Se llevó a cabo un estudio descriptivo, observacional y retrospectivo mediante la revisión de la base de datos y registros del servicio de emergencias del hospital, correspondientes al periodo comprendido entre enero 2012 y junio 2014, seleccionándose las atenciones debidas a patología reumatológica. Los datos fueron procesados mediante el programa estadístico SPSS 16.0.Resultados: Durante el periodo evaluado el número total de atenciones en el servicio de emergencias fue de 133484, correspondiendo 835 casos (0,63%) a diagnósticos reumatológicos segúnla Clasificación Internacionalde Enfermedades 10° (CIE-10). La mayoría de los pacientes fueron hombres (450, 53,08%) y la distribución por grupos etáreos fue: 1-4 años 327 (39,16%), 5-9 años 251 (30,02%), 10-14 años 158 (18,98%), mayores de 15 años 68 (8,11%) y menores de un año 32 (3,77%). Las 5 primeras causas de atenciones reumatológicas, de acuerdo al CIE-10, durante este período fueron: artritis reactiva 173 casos (20,72%), dolor en articulación 168 (20,12%), púrpura de Schönlein-Henoch (púrpura alérgica) 107 (12,81%), artritis séptica (artritis piógena) 89 (10,67%) y mialgias 77 (9,22%). El número de atenciones por problemas reumatológicos se mantuvo estable a través del tiempo, siendo de325 a345 casos por año.Conclusiones: Las atenciones debidas a patología reumatológica en el servicio de emergencias de un hospital pediátrico terciario como el nuestro son frecuentes y estables durante el transcurso del tiempo. Una adecuada evaluación inicial y un apropiado periodo de seguimiento aseguran un correcto diagnóstico y un tratamiento eficaz. Los pediatras que trabajan en el área de emergencias deberían estar capacitados en reumatología pediátrica

Infections in Moderate to Severe Psoriasis Patients Treated with Biological Drugs Compared to Classic Systemic Drugs: Findings from the BIOBADADERM Registry.

Information regarding the safety of biological drugs prescribed to psoriasis patients on daily and long-term bases is insufficient. We used data from the BIOBADADERM registry (Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases) to generate crude rates of infection during therapy with systemic drugs, including biological drugs (infliximab, etanercept, adalimumab, and ustekinumab) and nonbiological drugs (acitretin, cyclosporine, and methotrexate). We also calculated unadjusted and adjusted risk ratios (RRs) (with propensity score adjustment) of infection, serious infections, and recurrent infections of systemic therapies compared with methotrexate, using Poisson regression. Our study included records of 2,153 patients (7,867.5 person-years). The adjusted RR of overall infection was significantly increased in the groups treated with adalimumab with methotrexate (adjusted RR = 2.13, 95% confidence interval [CI] = 1.2-3.7), infliximab (adjusted RR = 1.71, 95% CI = 1.1-2.65), cyclosporine (adjusted RR = 1.58, 95% CI = 1.17-2.15), ustekinumab with methotrexate (adjusted RR = 1.56, 95% CI = 1.08-2.25), and etanercept (adjusted RR = 1.34, 95% CI: 1.02-1.76) compared with methotrexate alone. Cyclosporine had a significant risk of serious infection (adjusted RR = 3.12, 95% CI = 1.1-8.8), followed by adalimumab combined with methotrexate (adjusted RR = 3.28, 95% CI = 0.8-13.5). Adalimumab in combination with methotrexate had the highest risk of infection recurrence (adjusted RR = 4.33, 95% CI = 2.27-8.24)

Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis

Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti-interleukin-1β monoclonal antibody, in two trials.status: publishe