An Unusual U2AF2 Inhibits Splicing and Attenuates the Virulence of the Human Protozoan Parasite Entamoeba histolytica.

E. histolytica is the etiological agent of intestinal amebiasis and liver abscesses, which still poses public health threat globally. Metronidazole is the drug of choice against amebiasis. However, metronidazole-resistant amoebic clinical isolates and strains have been reported recently, challenging the efforts for amebiasis eradication. In search of alternative treatments, E. histolytica transcriptomes have shown the association of genes involved in RNA metabolism with the virulence of the parasite. Among the upregulated genes in amoebic liver abscesses are the splicing factors EhU2AF2 and a paralog of EhSF3B1. For this reason and because EhU2AF2 contains unusual KH-QUA2 (84KQ) motifs in its lengthened C-terminus domain, here we investigated how the role of EhU2AF2 in pre-mRNA processing impacts the virulence of the parasite. We found that 84KQ is involved in splicing inhibition/intron retention of several virulence and non-virulence-related genes. The 84KQ domain interacts with the same domain of the constitutive splicing factor SF1 (SF1KQ), both in solution and when SF1KQ is bound to branchpoint signal RNA probes. The 84KQ-SF1KQ interaction prevents splicing complex E to A transition, thus inhibiting splicing. Surprisingly, the deletion of the 84KQ domain in EhU2AF2 amoeba transformants increased splicing and enhanced the in vitro and in vivo virulence phenotypes. We conclude that the interaction of the 84KQ and SF1KQ domains, probably involving additional factors, tunes down Entamoeba virulence by favoring intron retention.

Dermatosis ampollosa hemorrágica por administración de heparinas de bajo peso molecular / Bullous hemorrhagic dermatosis induced by low molecular weight heparins

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Clinical course and risk factors for mortality from COVID-19 in patients with haematological malignancies.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) in haematological patients (HP) has not been comprehensively reported. METHODS: We analysed 39 patients with SARS-CoV-2 infection and haematological malignancies. Clinical characteristics and outcomes were compared to a matched control group of 53 non-cancer patients with COVID-19. Univariate and multivariate analyses were carried out to assess the risk factors associated with poor outcome. RESULTS: The most frequent haematological diseases were lymphoma (30%) and multiple myeloma (30%). Eighty-seven % HP developed moderate or severe disease. Patients with haematological malignancies had a significantly higher mortality rate compared to non-cancer patients (35.9% vs 13.2%; P = .003 (odds ratio 6.652). The worst outcome was observed in chronic lymphocytic leukaemia patients. Only age >70 years and C reactive protein >10 mg/dl at admission were associated with higher risk of death (odds ratio 34.86, P = .003 and 13.56,P = .03). Persistent viral sheddind was detected in 5 HP. Active chemotherapy, viral load at diagnosis and COVID-19 therapy were not predictors of outcome. CONCLUSION: Mortality of COVID-19 is significantly higher in patients with haematological malignancies compared to non-cancer patients. The impact of persistent viral shedding must be considered in order to re-start therapies and maintain infectious control measures.

Diagnostic performance of contrast-enhanced dual-energy spectral mammography (CESM): a retrospective study involving 644 breast lesions.

OBJECTIVE: To evaluate the diagnostic performance of contrast-enhanced dual-energy spectral mammography (CESM) in comparison with that of full-field digital mammography (FFDM), either alone or accompanied with breast ultrasound (BUS) in a large series of patients/breast lesions (n = 644). PATIENTS AND METHODS: In this retrospective study, five radiologists evaluated the lesions by three imaging modalities: FFDM, FFDM + BUS, and CESM and compared the imaging to the gold standard (histopathology or clinical follow-up). Diagnostic performance parameters and receiver operating characteristic (ROC) curves of CESM were calculated and compared to those of FFDM or FFDM + BUS (McNemar's test). Additionally, the reliability of tumor size measurement by CESM was compared with the histopathological measurement. RESULTS: The study included 218 benign and 426 malignant lesions. 85% of benign and 93% of malignant lesions were adequately identified using CESM. With respect to FFDM and FFDM + BUS, CESM significantly increased sensitivity to 93.2% (+ 10.7% and + 3.4%, respectively); specificity to 84.4% (+ 15.8% and + 1.7%, respectively); PPV to 92.3% (+ 26.8% and + 3.6%, respectively); NPV to 86.0% (+ 1.6% and + 1.8%, respectively); and accuracy to 90.2% (+ 15.8% and + 3.2%, respectively). In the ROC curves analyses, the comparison among the three AUC values was also statistically significant (p < 0.001). Good agreement between tumor diameters measured using CESM and histopathology was observed (Spearman's rank correlation, r = 0.891, p < 0.0001), although this technique tended to produce an overestimation of the size (+ 7 mm). CONCLUSIONS: CESM has high diagnostic accuracy and can be considered as a useful technique for the assessment of breast lesions.

A Case of a Concurrent and Co-Located Invasive Carcinoma and a Fibroadenoma to Illustrate the Potential of Dual-Energy, Contrast-Enhanced Digital Mammography on the Diagnosis of Complex Breast Lesions.

Up to 19% of breast malignancies may be missed by conventional imaging techniques, especially when they are concurrent or co-located with other benign lesions. However, more sensitive techniques, such as magnetic resonance imaging (MRI), are often too expensive for routine use in developing countries. Contrast-enhanced, dual-energy digital mammography (CESM) is a recently introduced imaging modality whose performance has been reported to be similar to that of MRI. Being much cheaper, CESM may constitute a good alternative for improving diagnostic sensitivity in these countries. In this paper, we present a challenging case of the concurrent and co-located presentation of a fibroadenoma and a triple negative invasive carcinoma of no special type (TNBC-NST). The malignancy was indistinguishable from the fibroadenoma by mammography. By ultrasound, a suspicious area was observed and biopsied, but the histopathology did not confirm a cancer diagnosis. As the suspicion was not confirmed, a second stage of the imaging diagnosis using CESM was recommended. This technique allowed clear visualization of the malignancy, which was finally excised by breast-conserving surgery. This case reveals the potential of CESM as an easy, rapid and inexpensive new technique for the diagnosis of malignancies that might easily remain occult to mammography plus breast ultrasound (BUS).

Is contrast-enhanced spectral mammography (CESM) helpful in differentiating diabetic mastopathy from breast carcinoma?

Diabetic mastopathy (DM) is a rare benign inflammatory disease of the breast, which nevertheless gives suspicious image of malignancy by breast ultrasound and mammography. MRI studies of this disease have indicated both nonspecific enhancement and non-enhancement of the lesion, depending on its degree of lymphocytic infiltration. This is the first case report discussing the appearances of DM on CESM, a novel mammographic technique.

Valoración fisiológica de un programa de actividad física en adultos / Physiological assessment of a exercise program in adults

El objetivo del presente trabajo fue evaluar el estado fisiológico antes y después de un programa de actividad física de 12 semanas de duración, de dos sesiones semanales de 45 a 60 minutos, consistente en realizar actividades y juegos de resistencia aeróbica, fuerza, estiramiento y relajación.Para la valoración fisiológica se utilizó el test de Andar 2 kilómetros (test UKK), con el que se obtuvo un índice de fitness y el consumo máximo de oxígeno, que reflejan el nivel de resistencia aeróbica, utilizando las siguientes variables: índice de masa corporal, edad, frecuencia cardiaca media y tiempo en realizar la prueba.Este estudio se realizó sobre una población de 39 personas, compuesta por 36 mujeres y 3 hombres, por lo que todos los resultados estadísticos se realizaron sobre este sexo.Los resultados muestran que el índice de UKK (de 70'26 +/- 18'77 a 80'28 +/- 13'32) Y el consumo máximo de oxígeno (de 19'47 +/- 7'62 a 22'98 +/- 5'81 mL/Kg/min) habían aumentado significativamente debido a que habían disminuido el tiempo de ejecución de la prueba, la frecuencia cardiaca promediada y el índice de masa corporal, y éste por disminución del peso corporal.La principal conclusión fue que tras el programa de actividad realizado se produjo un incremento de la resistencia aeróbica, que por definición, se produce cuando se realiza un mismo trabajo (2 kilómetros) a una mayor intensidad de esfuerzo o con una menor frecuencia cardiaca. Ambos situaciones se observan en los resultados recogidos al final del programa

The aim of this study was to assess aerobic capacity before and after a physical activity program twelve week lasting, twice weekly, 45 to 60 minutes per session, consisting in performing activities and games of aerobic resistance, force, stretching and relaxation.The 2-km Walking Test was used for physiological assessment and a fitness index and VO, max was obtained based on the following variables: body mass index, age, heart rate and time on the 2-km end. These parameters indicate the aerobic resistance level.This study was developed with 39 persons, 36 women and 3 men, so these stadistic results were carried out with only women.Results show that both, UKK index (from 70'26 +/- 18'77 to 80'28 +/- 13'32) and vo, max (from 19'47 +/- 7'62 to 22'98 +/- 5'81 mL/Kg/min), had increased significantly. The reason is that time at the end test, heart rate average and the body mass index had decreased, the last one due to diminishing weight.The main conclusion is that after the carried out activity program an increment of the aerobic resistance took place, this means that the same work is carried out (2 kilometers) to a higher intensity of effort or with a lower heart rateo The results show both situation