Impacto en la salud mental de los profesionales sanitarios que prestan asistencia a pacientes durante el brote del Covid-19 / Impact on the mental wellbeing of health professionals who provide care to patients during the Covid-19 outbreak

Las principales repercusiones de pandemias anteriores en el personal sanitario son los problemas de salud mental. Sin embargo, existe poca evidencia disponible relacionada a cómo el COVID-19 está afectando la salud mental en el personal sanitario. El objetivo de esta revisión de literatura fue analizar el impacto que ha tenido la pandemia en la salud mental de los profesionales de salud. Se realizó una revisión de literatura narrativa utilizando las bases de datos de Proquest y PubMed, 11 artículos fueron seleccionados de acuerdo al cumplimiento de los criterios definidos. Los trastornos mentales más frecuentes en el personal sanitario que trabaja directamente en la atención de pacientes Covid-19 son: el estrés, depresión, ansiedad y la angustia, insomnio, hiperactividad y baja calidad de vida, afectan también al personal sanitario. Estos trastornos mentales son provocados por diversos factores como el exceso de carga laboral, miedo a infectarse e infectar a sus familias, falta de medios de protección personal y temor de ser discriminados entre otros. La pandemia del COVID-19 afecta negativamente la salud mental de los profesionales de salud que trabajan directamente en la atención de pacientes, así también como la calidad de vida, por lo que es fundamental tomar acciones para proteger a los funcionarios de salud.

The main repercussions of previous pandemics on health workers are mental health problems. However, there is little evidence available related to how COVID-19 is affecting mental wellbeing in healthcare personnel. This literature review's objective was to analyze the impact that the pandemic has had on the mental wellbeing of health professionals. A narrative literature review was carried out using the Proquest and PubMed databases; 11 articles were selected according to the defined criteria' fulfillment. The most frequent mental disorders in health personnel who work directly in the care of Covid-19 patients are: stress, depression, anxiety and anguish, insomnia, hyperactivity, and low quality of life, which also affect health personnel. These mental disorders are caused by various factors such as excessive workload, fear of becoming infected and infecting their families, lack of means of personal protection, and fear of being discriminated against, among others. The COVID-19 pandemic negatively affects the mental wellbeing of health professionals who work directly in patient care and the quality of life, so it is essential to take action to protect health workers.

HDLive ultrasound images of ovarian dermoid cysts: diagnostic accuracy.

OBJECTIVE: To demonstrate that the use of 3D/4D HDLive increases the image quality in the diagnosis of benign cystic ovarian teratomas. MATERIALS AND METHODS: 3D/HDLive ultrasound (US) was used in 31 cases of suspected ovarian cystic teratoma using vaginal 2D US. The following pathognomonic images of mature cystic teratomas were considered for diagnosis: 1) a cystic, unilocular lesion with a densely echogenic tubercle (Rokitansky nodule); 2) a diffuse or partially echogenic mass usually demonstrating sound attenuation; 3) fluid-fluid/fat-fluid levels; 4) dermoid mesh with hyperechogenic calcifications indicating the presence of bone, teeth, or other ectodermally-derived structure; 5) multiple mobile spherical structures (fat globules). RESULTS: Dermoids present a wide spectrum of images depending on the predominant tissue type. In the vast majority of cases there are dense echogenic structures that correspond to complex masses of fatty tissue, sebum, hair, epithelial remnants, along with cartilage or bone. If we catalogue all the images together, the pathognomonic of dermoid are: 1) cystic or solid cystic lesions with a Rokitansky nodule, with bone, teeth or cartilage (six cases, 22.2%); 2) a solid mass with or without attenuation that corresponds with pure sebum (five cases, 18.5%); 3) a diffuse mass with fine bands that correspond with hair inside sebum (four cases, 12.9%) and that may form meshes or plugs corresponding with a mixture of fat, sebum, and hair (three cases, 11.5%). CONCLUSIONS: HDLive U.S. provides some images of exceptional quality that enhance the definition of the structures of these tumors (fat, hair, cartilage, bone, etc.) compared to 2D/3D/4D.

Snail1 controls TGF-ß responsiveness and differentiation of mesenchymal stem cells.

The Snail1 transcriptional repressor plays a key role in triggering epithelial-to-mesenchymal transition. Although Snail1 is widely expressed in early development, in adult animals it is limited to a subset of mesenchymal cells where it has a largely unknown function. Using a mouse model with inducible depletion of Snail1, here we demonstrate that Snail1 is required to maintain mesenchymal stem cells (MSCs). This effect is associated to the responsiveness to transforming growth factor (TGF)-ß1 that shows a strong Snail1 dependence. Snail1 depletion in conditional knockout adult animals causes a significant decrease in the number of bone marrow-derived MSCs. In culture, Snail1-deficient MSCs prematurely differentiate to osteoblasts or adipocytes and, in contrast to controls, are resistant to the TGF-ß1-induced differentiation block. These results demonstrate a new role for Snail1 in TGF-ß response and MSC maintenance.

Involvement of G protein and purines in Rhinella arenarum oocyte maturation.

We investigated the participation of G(αi) protein and of intracellular cAMP levels on spontaneous and progesterone-mediated maturation in Rhinella arenarum fully grown follicles and denuded oocytes. Although progesterone is the established maturation inducer in amphibians, Rhinella arenarum oocytes obtained during the reproductive period (competent oocytes) resume meiosis with no need for an exogenous hormonal stimulus if deprived of their enveloping follicular cells, a phenomenon called spontaneous maturation. In amphibian oocytes, numerous signalling mechanisms have been involved in the rapid, non-genomic, membrane effects of progesterone, but most of these are not fully understood. The data presented here demonstrate that activation of the G(αi) protein by Mas-7 induced maturation in non-competent oocytes and also an increase in GVBD (germinal vesicle breakdown) in competent oocytes. Similar results were obtained with intact follicles independent of the season. The activation of adenylyl cyclase (AC) by forskolin seems to inhibit both spontaneous and progesterone-induced GVBD. In addition, the high intracellular levels of cAMP caused by activation of AC by forskolin treatment or addition of db-cAMP inhibited maturation that had been induced by Mas-7 and in a dose-dependent manner. Treatment with H-89, a protein kinase A (PKA) inhibitor, was able to trigger GVBD in a dose-dependent manner in non-competent oocytes and increased the percentages of GVBD in oocytes competent to mature spontaneously. The results obtained with whole follicles and denuded oocytes were similar, which suggested that effects on AC and PKA were not mediated by follicle cells. The fact that Mas-7 was able to induce maturation in non-competent oocytes in a similar manner to progesterone and to increase spontaneous maturation suggests that G(αi) activation could be an important step in meiosis resumption. Thus, the decrease in cAMP as a result of the regulation of the G proteins on AC and the inactivation of PKA by H-89 could contribute to the activation of MPF (maturation promoting factor) and induce maturation of the oocytes of Rhinella arenarum.

Predicting ovarian reserve and reproductive outcome using antimüllerian hormone (AMH) and antral follicle count (AFC) in patients with previous assisted reproduction technique (ART) failure.

PURPOSE OF INVESTIGATION: The main objective of our prospective, observational, analytical research work was to determine whether Anti-Müllerian hormone (AMH) and antral follicle count (AFC) could be effectively used as predictors of ovarian reserve and, possibly, of reproductive outcome with ART. METHODS: We studied 143 IVF/ET cycles in patients with a previous history of ART failure, all of them supposed to be of poor prognosis, who had agreed to another ART attempt after knowing their AMH, AFC, and base hormone (FSH, LH, 17 beta-estradiol) levels. RESULTS: AMH and AFC showed a positive correlation with the number of oocytes retrieved (p = 0.0016) and (p < 0.0001), respectively and with percentage of MII oocytes, (p = 0.00756) and (p < 0.001). The combined use of these markers showed an area under the curve of 82.2% for oocytes retrieved. Our results shows a very high cancelation (22% of started cycles) and very low pregnancy rates (6.7% and 9.8%) in low and normoresponders, respectively. CONCLUSIONS: AMH levels and AFC are reliable indicators of ovarian reserve. Patients with ovarian reserve levels that predict a very low probability of success should be informed that the poor prognosis associated with these values may not justify the expense of IVF/ET.

Analysis of exosome release and its prognostic value in human colorectal cancer.

A significant proportion of extracellular nucleic acids in plasma circulate highly protected in tumor-specific exosomes, but it is unclear how the release of exosomes is modulated in carcinogenesis. We quantified by cytometry exosomes in plasma of 91 colorectal cancer patients to evaluate their potential as a tumor indicator and their repercussions on diagnosis and prognosis. We examined the involvement of TSAP6, a TP53-regulated gene involved in the regulation of vesicular secretion, in levels of circulating exosomes in plasma of colorectal patients and in HCT116 TP53-(wild-type and null) human colorectal cancer cell lines. The fraction of exosomes in cancer patients was statistically higher than in healthy controls (mean rank » 53.93 vs. 24.35). High levels of exosomes in plasma of patients correlated with high levels of carcino-embryonic antigen (P » 0.029) and with poorly differentiated tumors (P » 0.039) and tended to have shorter overall survival than patients with low levels (P » 0.056). Release of exosomes did not correlate with TSAP6 expression; and regulation of TSAP6 by TP53 was not shown either in tumor samples or in HCT116 cell lines. Although it was not suggested that the TP53/TSAP6 pathway regulates the release of exosomes into the plasma of colorectal cancer patients, the level of circulating exosomes may be used as a tumor indicator, because it correlates with poor prognosis parameters and shorter survival.

Aberrant epigenetic regulation of bromodomain BRD4 in human colon cancer.

The bromodomain protein BRD4 is involved in cell proliferation and cell cycle progression, primarily through its role in acetylated chromatin-dependent regulation of transcription at targeted loci. Here, we show that BRD4 is frequently downregulated by aberrant promoter hypermethylation in human colon cancer cell lines and primary tumors. Ectopic re-expression of BRD4 in these colon cancer cell lines markedly reduced in vivo tumor growth, suggesting a role of BRD4 in human colon cancer.

Participation of MAPK, PKA and PP2A in the regulation of MPF activity in Bufo arenarum oocytes.

The objectives of the present paper were to study the involvement and possible interactions of both cAMP-PKA and protein phosphatases in Bufo arenarum oocyte maturation and to determine if these pathways are independent or not of the MAP kinase (MAPK) cascade. Our results indicated that the inhibition of PKA by treatment with H-89, an inhibitor of the catalytic subunit of PKA, was capable of inducing GVBD in a dose-dependent manner by a pathway in which Cdc25 phosphatase but not the MAPK cascade is involved. The injection of 50 nl of H-89 10 µM produced GVBD percentages similar to those obtained with treatment with progesterone. In addition, the assays with okadaic acid (OA), a PP2A inhibitor, significantly enhanced the percentage of oocytes that resumed meiosis by a signal transducing pathway in which the activation of the MEK-MAPK pathway is necessary, but in which Cdc25 phosphatase was not involved. Treatment with H-89, was able to overcome the inhibitory effect of PKA on GVBD; however, the inhibition of Cdc25 activity with NaVO3 was able to overcome the induction of GVBD by H-89. Although the connections between PKA and other signalling molecules that regulate oocytes maturation are still unclear, our results suggest that phosphatase Cdc25 may be the direct substrate of PKA. In Xenopus oocytes it was proposed that PP2A, a major Ser/Thr phosphatase present, is a negative regulator of Cdc2 activation. However, in Bufo arenarum oocytes, inhibition of Cdc25 with NaVO3 did not inhibit OA-induced maturation, suggesting that the target of PP2A was not the Cdc25 phosphatase. MAPK activation has been reported to be essential in Xenopus oocytes GVBD. In B. arenarum oocytes we demonstrated that the inhibition of MAPK by PD 98059 prevented the activation of MPF induced by OA, suggesting that the activation of the MAPK cascade produced an inhibition of Myt1 and, in consequence, the activation of MPF without participation of the Cdc25 phosphatase. Our results suggest that in incompetent oocytes of B. arenarum two signal transduction pathways may be involved in the control of MPF activation: (1) the inhibition of phosphatase 2A that through the MEK-MAPK pathway regulates the activity of the Myt1; and (2) the inhibition of AMPc-PKA, which affects the activity of the Cdc25 phosphatase.

Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival.

The identification of tumour biomarkers that detect the presence of disease using noninvasive diagnostic procedures is a key part of cancer research. We determined in plasma the vesicle-related microRNA (miRNA) expression profile of nonsmall cell lung cancer (NSCLC) and evaluate whether plasma miRNAs can be both discriminating (between patients and healthy controls) and prognostic markers. 365 human miRNAs were analysed by Taqman® low-density arrays (Applied Biosystems, Foster City, CA, USA) in the plasma from 28 NSCLC patients and 20 controls. Five selected miRNAs (let-7f, miR-20b, miR-30e-3p, miR-223 and miR-301) were validated independently by real-time PCR in plasma from 78 NSCLC and 48 controls and correlated with pathologic parameters and survival. Levels of let-7f, miR-20b and miR-30e-3p were decreased in plasma vesicles of NSCLC patients. Moreover, levels of let-7f and miR-30e-3p distinguished between two groups of patients for stage of disease and therefore possibility of surgery. Plasma levels of miR-30e-3p and let-7f were associated with short disease-free survival and overall survival, respectively. NSCLC patients and healthy controls differ in vesicle-related miRNAs in plasma. Levels of let-7f and miR-30e-3p in NSCLC patients are associated with poor outcome. Thus, plasma vesicle-related miRNAs obtained by noninvasive methods could serve as circulating tumour biomarkers of discriminating and prognostic value.

EPAS1 mRNA in plasma from colorectal cancer patients is associated with poor outcome in advanced stages.

The presence of free nucleic acids in plasma has been detected in cancer patients and is associated with poor prognosis. In the present study, the mRNA levels of three genes (EPAS1, KIAA0101 and UBE2D3) in plasma from colorectal cancer patients were analyzed. These genes were selected from a previous study of genomic profiles, discriminating between healthy controls and colorectal cancer patients. mRNA levels were analyzed by real-time PCR in the plasma of 154 patients with colorectal cancer. The association of plasma mRNA levels with clinicopathological parameters and patient survival were analyzed. High levels of EPAS1 in the plasma were associated with patients aged over 50 years, relapse of disease and patient mortality. When patients were divided into two groups, early (I and II) and advanced (III and IV) stages, an association was observed between high levels of EPAS1 mRNA and worse disease-free and overall survival in advanced stages. The expression of KIAA0101 and UBE2D3 was not associated with poor prognosis. Thus, our results suggest that EPAS1 mRNA levels may be an indicator of poor prognosis in colorectal cancer patients at advanced stages, obtained by a non-invasive method.

SPROUTY-2 and E-cadherin regulate reciprocally and dictate colon cancer cell tumourigenicity.

SPROUTY-2 (SPRY2) regulates receptor tyrosine kinase signalling and therefore cell growth and differentiation. In this study, we show that SPRY2 expression in colon cancer cells is inhibited by the active vitamin D metabolite 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) through E-cadherin-dependent and -independent mechanisms. In turn, SPRY2 represses both basal and 1,25(OH)(2)D(3)-induced E-cadherin expression. In line with this, SPRY2 induces ZEB1 RNA and protein, but not that of other epithelial-to-mesenchymal transition inducers that repress the CDH1/E-cadherin promoter. Consistently, SPRY2 and E-cadherin protein levels inversely correlate in colon cancer cell lines and xenografted tumours. Moreover, SPRY2 knockdown by small hairpin RNA increases CDH1/E-cadherin expression and, reciprocally, CDH1/E-cadherin knockdown increases that of SPRY2. In colon cancer patients, SPRY2 is upregulated in undifferentiated high-grade tumours and at the invasive front of low-grade carcinomas. Quantification of protein expression in 34 tumours confirmed an inverse correlation between SPRY2 and E-cadherin. Our data demonstrate a tumourigenic action of SPRY2 that is based on the repression of E-cadherin, probably by the induction of ZEB1, and a reciprocal regulation of SPRY2 and E-cadherin that dictates cell phenotype. We propose SPRY2 as a candidate novel marker for high-grade tumours and a target of therapeutic intervention in colon cancer.

Substrate vibrations in the scorpion Centruroides margaritatus (Scorpiones: Buthidae) during courtship / Vibraciones del sustrato en el escorpión Centruroides margaritatus (Scorpiones: Buthidae) durante el cortejo

Mating behavior in Centruroides margaritatus, as in other scorpion species, includes a series of rapid rocking or shaking movements of the male ("juddering"). It has been suggested that substrate vibrations are generated by juddering and that females respond to them by approaching the male, but its functional significance remains little studied. For the first time, substrate vibrations produced by males during courtship in Centruroides margaritatus are documented. The male started juddering after his first physical contact with the female and only one type of male vibratory signal was registered. The signal is produced during a series of rapid shaking of the male’s body from front to rear and consists of multiple short pulses. Each pulse is called a judder and several judders "a series". The average duration of each judder was 0.018±0.009s (n=50) with an interval of 0.028±0.013s (n=50); the average duration of each series of judders was 4.2±3.5s with an interval between series of 3.5±6.3s and a rate of 0.21±0.17 series per second. The females responded in 72% of the time to the males juddering. Rev. Biol. Trop. 57 (Suppl. 1): 267-274. Epub 2009 November 30.

El comportamiento de apareamiento en Centruroides margaritatus como en otras especies del escorpiones, incluye una serie de oscilaciones rápidas hacia adelante y hacia atrás del cuerpo del macho (juddering). Se ha especulado que tales oscilaciones generan vibraciones en el substrato y las hembras pueden responder a ellas aproximándose al macho, pero su significado funcional sigue siendo poco estudiado. Por primera vez, las vibraciones del substrato producidas por los machos durante el comportamiento de cortejo de Centruroides margaritatus son documentadas. El macho comenzó las vibraciones después de su primer contacto físico con la hembra y sólo se registró un tipo de señal vibratoria. La señal se produce durante una serie de rápidas sacudidas del cuerpo del macho de adelante hacia atrás y se compone de múltiples pulsos cortos. La duración media de cada pulso fue 0.018±0.009s (n = 50) con un intervalo de 0.028±0.013s (n=50); la duración media de cada serie de pulsos fue de 4.2±3.5s, con un intervalo entre las series de 3.5±6.3s y una tasa de 0.21±0.17 serie por segundo. Las hembras respondieron en un 72% del tiempo a las sacudidas de los machos. Se discute acerca de su posible función como señal.

SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue.

SNAI1, ZEB1, E-cadherin (CDH1), and vitamin D receptor (VDR) genes regulate the epithelial-mesenchymal transition (EMT) that initiates the invasion process of many tumor cells. We hypothesized that this process could also affect the behavior of normal cells adjacent to the tumor. To verify this hypothesis, the expression level of these genes was determined by quantitative RT-PCR in tumor, normal adjacent, and normal distant tissues from 32 colorectal cancer (CC) patients. In addition, we extended the study to human HaCaT normal keratinocytes and SW480-ADH colon cancer cells co-cultured with SW480-ADH cells overexpressing the mouse Snai1 gene. Of 18 CC cases with SNAI1 expression in tumor tissue, five also had SNAI1 in normal adjacent tissue (NAT). Expression of SNAI1 in tumor tissue correlated with downregulation of CDH1 and VDR genes in both tumor (P=0.047 and P=0.014, respectively) and NAT lacking SNAI1 expression (P=0.054 and P=0.003). ZEB1 expression was directly related to VDR expression in tumor tissue (r=0.39; P=0.027) and inversely to CDH1 in NAT (r=-0.46; P=0.010). CDH1 and VDR were also downregulated in SW480-ADH and MaCaT cells, respectively, when they were co-cultured with Snai1-expressing cells. Furthermore, cytokine analysis showed differences in the conditioned media obtained from the two cell types. These results indicate that histologically normal tissue adjacent to tumor tissue expressing the EMT-inducing gene SNAI1 shows alterations in the expression of epithelial differentiation genes such as CDH1 and VDR.

Primary immunodeficiency diseases: a practical guide for clinicians.

Primary immunodeficiency diseases (PIDs) are genetically determined disorders of the immune system resulting in greatly enhanced susceptibility to infectious disease, autoimmunity and malignancy. While individual PIDs are rare, as a group, it is estimated that between 1:2000 and 1:10 000 live births are affected by a PID. Moreover, PIDs can present at any age from birth to adulthood, posing a considerable challenge for the practising physician to know when and how to work-up a patient for a possible immune defect. In this review, we outline the basic organisation of the human immune system and the types of infections that occur when elements of the immune system are dysfunctional. Importantly, we provide practical guidelines for identifying patients who should be referred for assessment of possible immunodeficiency and an overview of screening investigations and effective therapeutic options available for these patients.

Involvement of GABAA receptor in Bufo arenarum oocyte maturation.

Amphibian oocytes meiotic arrest is released under the stimulus of progesterone; this hormone interacts with the oocyte surface and starts a cascade of events leading to the activation of a cytoplasmic maturation promoting factor (MPF) that induces germinal vesicle breakdown (GVBD), chromosome condensation and extrusion of the first polar body. The aim of this work was to determine whether the activation of a GABAA receptor is able to induce GVBD in fully grown denuded oocytes of Bufo arenarum and to analyse its possible participation in progesterone-induced maturation. We also evaluated the role of purines and phospholipids in the maturation process induced by a GABAA receptor agonist such as muscimol. Our results indicated that the activation of the GABAA receptor by muscimol induces maturation in a dose- and time-dependent manner and that this activation is a genuine maturation that enables oocytes to form pronuclei. Assays with a receptor antagonist, picrotoxine, showed that the maturation induced by muscimol was inhibited. Treatment with picrotoxine, however, shows that the participation of GABAA receptor in progesterone-induced maturation is not significant. In addition, our results indicate that high intracellular levels of purines obtained by the use of db-AMPc and theophylline or the inhibition of the phosphatidylinositol 4,5-bisphosphate (PIP2 hydrolysis by neomycin and PIP2 turn over by LiCl, respectively, inhibited the maturation induced by muscimol. Treatment with H-7 indicated, however, that PKC activation is not necessary for GVBD induced by the GABAA receptor agonist. Results suggest that the transduction pathway used by the GABAA receptor to induce maturation is different from those used by progesterone.

DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D3.

Aberrant activation of the Wnt/beta-catenin signaling pathway is a hallmark of colon cancer. We show that the Wnt antagonist DICKKOPF-4 (DKK-4) gene is repressed by 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) in human colon cancer cells. This effect correlated with the inhibition of the DKK-4 promoter. Chromatin immunoprecipitation assays revealed that 1,25(OH)2D3 induces early and transient binding of the vitamin D receptor (VDR) and the SMRT corepressor to the region adjacent to the transcription start site of DKK-4. Additionally, we demonstrate that the DKK-4 gene is a new downstream target of TCF/beta-catenin. Remarkably, expression of DKK-4 messenger RNA (mRNA) was not detected in a series of 29 human normal (N) colon biopsies but expression was upregulated in all the matched tumour (T) tissues. An inverse correlation existed between the expression of DKK-4 and VDR RNA in the Ts. Ectopic DKK-4 expression increased the migration and invasion properties of colon cancer cells and conditioned media (CM) from DKK-4-expressing cells enhanced the capacity to migrate and form capillary-like tubules of human primary microvascular endothelial cells. In conclusion, DKK-4 is upregulated in colon cancer and is associated with the acquisition of malignant properties by neoplastic cells. DKK-4 downregulation is a novel effect of 1,25(OH)2D3 that may contribute to its anticancer action.

The presence of an intronic deletion in p73 and high levels of ZEB1 alter the TAp73/DeltaTAp73 ratio in colorectal carcinomas.

TAp73 variants largely mimic p53 suppressor activities, while DeltaTAp73 forms act as oncogenes through the inactivation of p53 and TAp73. The present study analysed how TAp73 and DeltaTAp73 levels might be affected by the presence of a 73 bp deletion in a regulatory region of p73. The clinical relevance of this deletion was also examined. ZEB1 can bind to the region repressing p73 transcription in vitro. The relationship between ZEB1 and p73 variant expression levels was studied in the context of this deletion and the levels of the ZEB1 cofactors p300 and CtBP. Tumour and normal tissue from 81 colorectal cancer patients was analysed to evaluate firstly the levels of TAp73, DeltaTAp73 (DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73), ZEB1, p300, and CtBP by quantitative real-time RT-PCR, and secondly the presence of the 73 bp deletion. Tumour characteristics were examined in each patient. Suppressor and oncogenic isoforms of p73 were co-up-regulated in tumour tissues. Overexpression of p73 variants was associated with adverse tumour features. The 73 bp deletion was present in 40% of the patients and was associated with adverse pathological parameters of the tumours and also with TAp73 down-regulation. In those cases harbouring the deletion, the levels of ZEB1 and those of DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73 correlated directly. Variations in the concentration of p300 affected the observed correlations between ZEB1 and the different p73 variants. In conclusion, in colorectal cancer, the 73 bp deletion in the first intron of the p73 gene and different expression levels of ZEB1 and p300 may act in concert to affect the ratio of TAp73/DeltaTAp73 forms, favouring p73 oncogenic variants. In addition, up-regulation of p73 oncogenic isoforms predicts a poor prognosis based on its relationship with advanced tumour stage.