Reliability, usability, and efficiency of video versus print instructions to teach parents a procedural task: A cross-sectional study.

OBJECTIVE: To compare the reliability, usability, and efficiency of video versus print instructions to teach parents a procedural measurement task. We hypothesized that videos would outperform print in all outcomes. STUDY DESIGN: This cross-sectional study included parents/caregivers of children aged 0-18 years with deep vein thrombosis attending the Thrombosis Clinic at The Hospital for Sick Children for post-thrombotic syndrome (PTS) assessment. Participants were randomly assigned to three instruction types: (i) video, which followed the technique used by clinicians; (ii) long pamphlet, which also followed the clinicians' technique; and (iii) short pamphlet, which explained a simplified technique. After measuring their children's arms or legs using the randomly assigned material, participants completed a usability questionnaire. The reliability of the instructions was estimated by comparing parents/caregivers versus clinicians' measurements using the intraclass correlation coefficient (ICC). Reliability, usability, and efficiency (time to task completion) were compared among the three instruction types. RESULTS: In total, 92 participants were randomized to video (n = 31), long pamphlet (n = 31), and short pamphlet (n = 30). While the video had the highest usability, the short pamphlet was the most reliable and efficient. ICCs were .17 (95% confidence interval [CI]: .00-.39) for the video, .53 (95% CI: .30-.72) for the long pamphlet, and .70 (95% CI: .50-.81) for the short pamphlet. CONCLUSION: Although the video had higher usability, the short/simplified print instruction was more reliable and efficient. However, the reliability of the short pamphlet was only moderate/good, suggesting that whenever possible, measurements should still be obtained by trained clinicians.

The Mexican consensus on fecal incontinence.

Fecal incontinence is the involuntary passage or the incapacity to control the release of fecal matter through the anus. It is a condition that significantly impairs quality of life in those that suffer from it, given that it affects body image, self-esteem, and interferes with everyday activities, in turn, favoring social isolation. There are no guidelines or consensus in Mexico on the topic, and so the Asociación Mexicana de Gastroenterología brought together a multidisciplinary group (gastroenterologists, neurogastroenterologists, and surgeons) to carry out the «Mexican consensus on fecal incontinence¼ and establish useful recommendations for the medical community. The present document presents the formulated recommendations in 35 statements. Fecal incontinence is known to be a frequent entity whose incidence increases as individuals age, but one that is under-recognized. The pathophysiology of incontinence is complex and multifactorial, and in most cases, there is more than one associated risk factor. Even though there is no diagnostic gold standard, the combination of tests that evaluate structure (endoanal ultrasound) and function (anorectal manometry) should be recommended in all cases. Treatment should also be multidisciplinary and general measures and drugs (lidamidine, loperamide) are recommended, as well as non-pharmacologic interventions, such as biofeedback therapy, in selected cases. Likewise, surgical treatment should be offered to selected patients and performed by experts.

Active immunization with a structurally aggregated PD-L1 antigen breaks T and B immune tolerance in non-human primates and exhibits in vivo anti-tumoral effects in immunocompetent mouse tumor models.

Despite the clinical success of the programmed death ligand 1 (PD-L1) blocking therapy in cancer treatment, only a subset of patients exhibits durable responses, therefore further exploration of other immunotherapeutic alternatives are needed. This paper reported the development of the PKPD-L1Vac vaccine, a new protein vaccine candidate that uses aluminum phosphate as an adjuvant and as an antigen the extracellular domain of human PD-L1 fused to a 47 amino-terminal portion of the LpdA protein from N. meningitides (PKPD-L1). The PKPD-L1 antigen has different physical and biological characteristics than those found in the natural molecule and in others PD-L1 vaccine candidates. The quimeric protein has a reduced binding capacity to the PD-1 and CD80 receptors to decrease their pro-tumoral activity. Besides, the distinctive feature of the PKPD-L1 polypeptide to be structurally aggregated could be desirable for its immunogenic properties. PKPD-L1Vac elicited anti-PD-L1-specific IgG antibodies and T lymphocyte-mediated immunity in mice and non-human primates. The vaccine administration demonstrated antitumor activity on CT-26 and B16-F10 primary tumor models in mice. Moreover, the immunization with PKPD-L1Vac increased the tumor-infiltrating lymphocytes and decreased the proportion of CD3+CD8+PD1+high anergic T cells in CT-26 tumor tissues, suggesting that the vaccine may remodel the tumor microenvironment. In summary, the PKPD-L1Vac vaccine exhibits very promising preclinical results and deserves to move forward to a phase I clinical trial.

Natural isoquinoline alkaloids: Pharmacological features and multi-target potential for complex diseases.

Complex diseases such as neurodegenerative disorders and cancer constitute a growing public health problem due to the rising incidence and lack in effective therapies. Since pharmacotherapy based on a single target has been insufficient for drug development in complex diseases, the emerging multi-target approach is a promising strategy for the search of new drug candidates. Plant-derived isoquinoline alkaloids comprise a vast source of multimodal agents with unique structural diversity, and variated range of pharmacological activities. This review offers an exhaustive compilation of the pharmacological relevance and multi-target potential of natural isoquinolines, emphasizing their features and promising activity in complex diseases such as Alzheimer, Parkinson, and Cancer. Selected examples were discussed in depth to illustrate the most relevant structural motifs and their possible relationship with the multimodal activity offering a comprehensive baseline in the search and optimization of isoquinoline scaffolds with polypharmacological potential for complex diseases.

Molecular analysis in cytological samples obtained by endobronchial or oesophageal ultrasound guided needle aspiration in non-small cell lung cancer.

INTRODUCTION: Cytological samples obtained by endobronchial ultrasound (EBUS) are capital for diagnosis, staging and molecular profile in non-small cell lung carcinoma (NSCLC). OBJECTIVE: To assess the success rate of complete, partial and individual of molecular analysis in samples obtained by EBUS-guided transbronchial needle aspiration (TBNA) and/or by oesophageal ultrasound-guided fine needle aspiration with an echobronchoscope (EUS-B-FNA) in patients with NSCLC. METHODS: Prospective study including 90 patients with non-squamous NSCLC, or non-smoking squamous. Cytological samples were classified into two groups. Group 1: PEN membrane slide and/or cell blocks for the determination of mutations of EGFR, KRAS, ERBB2 and BRAF. Group 2: silane coated slides or cell blocks for rearrangements of ALK, ROS1 and MET amplification. RESULTS: The success rate was 78.6% for 4 molecular alterations (EGFR, KRAS, ALK and ROS1), and 44% for 7 determinations. The individual success rate for EGFR was 97%, KRAS 96.3%, ALK 85%, ROS1 82.3%, ERBB2 71.4%, BRAF 67.7% and MET 81.1%. There were no significant differences (p=0.489) in the number of molecular analyses (1-3 vs. 4) in group 1, depending on the types of samples (cell block vs. PEN membrane slide vs. cell block and PEN membrane slide). CONCLUSIONS: In patients with NSCLC, the cytological material obtained by ultrasound-guided needle aspiration is sufficient for individual and partial molecular analysis in the vast majority of cases. Membrane slides such as cell blocks are valid samples for molecular analysis.

Cardiovascular and Respiratory Interactions in Idiopathic Pulmonary Fibrosis by Extended Partial Directed Coherence: Short-term Effects of Supplemental Oxygen.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that can lead to chronic arterial hypoxemia, hypercapnia, and dyspnea. To improve clinical symptoms in IPF patients, supplemental oxygen (SupplO2) has been prescribed with the aim to maintain SpO2 level, and consequently to relieve dyspnea, increase physical activity and improve quality of life. In this study, we investigated the effect of disease and short-term SupplO2 on cardiovascular and respiratory autonomic regulation. Linear and nonlinear indices were extracted from the beat-to-beat variability of heart rate (HR), systolic (SYS) blood pressure and respiration (RESP) in IPF patients and healthy subjects spontaneously breathing ambient air (AA) and during SupplO2 at 3 L/min. It was found that the effects on autonomic nervous systems (ANS) regulation were better demonstrated by the Granger causality (GC) method. GC was significantly higher (p<0.01) in patients compared to controls for the interactions RESP→SYS and BBI→SYS.Clinical Relevance-Short-term SupplO2 in IPF could adversely affect systolic blood pressure variability in particular. This study may help in the management of SupplO2 administration.

The LPA3 Receptor: Regulation and Activation of Signaling Pathways.

The lysophosphatidic acid 3 receptor (LPA3) participates in different physiological actions and in the pathogenesis of many diseases through the activation of different signal pathways. Knowledge of the regulation of the function of the LPA3 receptor is a crucial element for defining its roles in health and disease. This review describes what is known about the signaling pathways activated in terms of its various actions. Next, we review knowledge on the structure of the LPA3 receptor, the domains found, and the roles that the latter might play in ligand recognition, signaling, and cellular localization. Currently, there is some information on the action of LPA3 in different cells and whole organisms, but very little is known about the regulation of its function. Areas in which there is a gap in our knowledge are indicated in order to further stimulate experimental work on this receptor and on other members of the LPA receptor family. We are convinced that knowledge on how this receptor is activated, the signaling pathways employed and how the receptor internalization and desensitization are controlled will help design new therapeutic interventions for treating diseases in which the LPA3 receptor is implicated.

Outcomes of radiofrequency ablation for anal high-grade squamous intraepithelial lesions.

BACKGROUND: Radiofrequency ablation (RFA) of high-grade squamous intraepithelial lesions (HSIL) is a promising minimally invasive technique but its oncologic and functional outcomes are not well studied. The primary outcome was the efficacy of RFA, and the secondary outcomes were the functional and anatomical anal changes related to RFA. METHODS: This was a retrospective analysis of our prospectively collected database of patients who had RFA for HSIL at our institution, between August 2018 and March 2020. To be eligible for RFA, all patients had impairment of their immune function. Targeted ablation was applied in all cases, with 5 overlapping pulsations at the targeted HSILs (delivering 12 J/cm2 per application) followed by circumferential, 2-pulsation (12 J/cm2) overlapping anal ablation, to cover the entire anal transition zone. Patients were assessed for recurrence or metachronous disease at 3-month intervals by means of high-resolution anoscopy (HRA) and targeted biopsies. Anorectal manometry, endoanal ultrasound, the 36-Item Short Form and Massachusetts General Hospital-Sexual Functioning Questionnaire (MGH-SFQ) were assessed at baseline and 12 months after intervention. RESULTS: We included a total of 12 patients with anal HSILs. The mean age was 38.6 (± 7.68) years, and 7 (58.3%) were males. Six were HIV positive, 2 had a primary immunodeficiency disease, and 4 were receiving immunosuppressive therapy. A mean of 2.1 anal HSILs per patient were treated. At 12 months, high-resolution anoscopy showed that 7/12 (58.3%) patients had normal high-resolution anoscopy, 3/12 patients had recurrent HSILs, and 2/12 had a persistent lesion. Those lesions were treated with electrocautery, and reached complete response in the following the 6 months (total of 18 months). In particular, there were no metachronous lesions detected. Patients reported moderate to severe pain during the first 24 h after RFA, but only mild discomfort was present at 30 days. Patients were asymptomatic at their 6- and 12-month visits. RFA was not associated with changes in anorectal manometry or ultrasound examination. The 36-SF survey reported improvement in the general health domain (p = 0.038), while the MGH-SFQ showed improvements in sexual function. CONCLUSIONS: In this study, targeted plus circumferential RFA had a 58.3% efficacy rate for the treatment of anal HSIL in immunocompromised patients, achieving 100% eradication after adding electrocautery ablation. No metachronous lesions were detected. Patients presented relatively mild symptoms after the procedure, no changes in anorectal anatomy or function, and some improvements in their sexual function. These results seem promising in light of the high recurrence reported after HSIL treatment. Larger studies are needed to validate our results.

[Axillary web syndrome following breast cancer surgery. Rare variant with subcutaneous nodules]. / Síndrome axillary web tras cirugía de cáncer de mama. Variante rara con nódulos subcutáneos.

We describe the case of a 49-year-old woman who, after surgical treatment of breast cancer, developed axillary web syndrome (AWS) followed, 3 weeks later, by the appearance of soft and painless subcutaneous nodules along the cords and close to the flexure of the elbow. After tests (soft tissue and Doppler ultrasound), a dermal/subcutaneous or neoplastic cause was ruled out, although a cephalic and ulnar venous thrombosis was revealed. Anticoagulant medication was prescribed, with disappearance of the nodules 3-4 weeks later and improvement of AWS. The symptoms, clinical course, diagnostic tests, as well as the published evidence, helped to establish a diagnosis of AWS with subcutaneous nodules. AWS is an early complication after axillary surgery, which is well known among breast cancer professionals and whose diagnosis is based on clinical presentation. Its association with subcutaneous nodules is one of its rare variants and requires compulsory complementary studies to exclude other causes. Like AWS, nodules are believed to be due to lymphatic vessel thrombosis.

S-adenosyl-L-methionine (SAMe) halts the autoimmune response in patients with primary biliary cholangitis (PBC) via antioxidant and S-glutathionylation processes in cholangiocytes.

S-adenosyl-L-methionine is an endogenous molecule with hepato-protective properties linked to redox regulation and methylation. Here, the potential therapeutic value of SAMe was tested in 17 patients with PBC, a cholestatic disease with autoimmune phenomena targeting small bile ducts. Nine patients responded to SAMe (SAMe responders) with increased serum protein S-glutathionylation. That posttranslational protein modification was associated with reduction of serum anti-mitochondrial autoantibodies (AMA-M2) titers and improvement of liver biochemistry. Clinically, SAMe responders were younger at diagnosis, had longer duration of the disease and lower level of serum S-glutathionylated proteins at entry. SAMe treatment was associated with negative correlation between protein S-glutathionylation and TNFα. Furthermore, AMA-M2 titers correlated positively with INFγ and FGF-19 while negatively with TGFß. Additionally, cirrhotic PBC livers showed reduced levels of glutathionylated proteins, glutaredoxine-1 (Grx-1) and GSH synthase (GS). The effect of SAMe was also analyzed in vitro. In human cholangiocytes overexpressing miR-506, which induces PBC-like features, SAMe increased total protein S-glutathionylation and the level of γ-glutamylcysteine ligase (GCLC), whereas reduced Grx-1 level. Moreover, SAMe protected primary human cholangiocytes against mitochondrial oxidative stress induced by tBHQ (tert-Butylhydroquinone) via raising the level of Nrf2 and HO-1. Finally, SAMe reduced apoptosis (cleaved-caspase3) and PDC-E2 (antigen responsible of the AMA-M2) induced experimentally by glycochenodeoxycholic acid (GCDC). These data suggest that SAMe may inhibit autoimmune events in patients with PBC via its antioxidant and S-glutathionylation properties. These findings provide new insights into the molecular events promoting progression of PBC and suggest potential therapeutic application of SAMe in PBC.

Canonical and non-canonical Wnt signaling are simultaneously activated by Wnts in colon cancer cells.

The Wnt signaling pathway is a crucial regulator of the intestinal epithelium homeostasis and is altered in most colon cancers. While the role of aberrant canonical, ß-catenin-dependent Wnt signaling has been well established in colon cancer promotion, much less is known about the role played by noncanonical, ß-catenin-independent Wnt signaling in this type of cancer. This work aimed to characterize the noncanonical signal transduction pathway in colon cancer cells. To this end, we used the prototype noncanonical ligand, Wnt5a, in comparison with Wnt3a, the prototype of a canonical ß-catenin activating ligand. The analysis of the expression profile of Wnt receptors in colon cancer cell lines showed a clear increase in both level expression and variety of Frizzled receptor types expressed in colon cancer cells compared with non-malignant cells. We found that Wnt5a activates a typical Wnt/Ca++ - noncanonical signaling pathway in colon malignant cells, inducing the hyperphosphorylation of Dvl1, Dvl2 and Dvl3, promoting Ca++ mobilization as a result of phospholipase C (PLC) activation via pertussis toxin-sensitive G-protein, and inducing PLC-dependent cell migration. We also found that while the co-receptor Ror2 tyrosine kinase activity is not required for Ca++ mobilization-induced by Wnt5a, it is required for the inhibitory effects of Wnt5a on the ß-catenin-dependent transcriptional activity. Unexpectedly, we found that although the prototype canonical Wnt3a ligand was unique in stimulating the ß-catenin-dependent transcriptional activity, it also simultaneously activated PLC, promoted Ca++ mobilization, and induced Rho kinase and PLC-dependent cell migration. Our data indicate, therefore, that a Wnt ligand can activate at the same time the so-called Wnt canonical and noncanonical pathways inducing the formation of complex signaling networks to integrate both pathways in colon cancer cells.

Diabetes is associated with a higher risk of mortality among women in a middle-income country: Results form the Mexican Teacher's cohort study.

AIMS: In Mexico City, the mortality rate among patients with diabetes appears to be four times that of people without diabetes. Our study aimed to refine analyses of the impact of diabetes on mortality in a large cohort of women from different areas in Mexico with healthcare insurance. METHODS: Our study followed 111,299 women with comprehensive healthcare coverage from the Mexican Teachers' Cohort. After a median follow-up of 7.8years, 5514 (5%) prevalent self-reported diabetes cases and 4023 incident cases were identified, while deaths were identified through employers' databases and next-of-kin reports, with dates and causes of death for 1121 women obtained from mortality databases. Hazard ratios (HRs) for total and cause-specific mortality were estimated by Cox regression models, using follow-up time as the time scale and allowing for time-variable diabetes status after adjusting for age, socioeconomic status, use of health services, and anthropometric and lifestyle variables. RESULTS: In multivariable-adjusted models, the HR for all-cause mortality was 3.28 (95% CI: 2.86-3.75) in women with vs. without diabetes. The impact of diabetes on mortality was higher in rural vs. urban areas (HR: 4.72 vs. 2.98, respectively). HRs were 1.57 and 23.44 for cancer and renal disease mortality, respectively. CONCLUSION: In women with healthcare coverage in Mexico, the magnitude of the association between diabetes and all-cause mortality was higher than that observed in high-income countries, but less than what has previously been reported for Mexico. Such elevated mortality suggests a lack of adequate access to quality diabetes care in the population despite comprehensive healthcare coverage.

Measurement of percentage dose at the surface for a 6 MV photon beam.

AIM: To evaluate if a radiochromic film (RF) Gafchromic EBT3 is suitable for surface dose measurements of radiotherapy treatments performed with a 6 MV linear accelerator. Two aspects of RF were analyzed, beam energy dependence and surface dose determination. BACKGROUND: The measurements done at the surface or near the radiation source are done without charged electronic equilibrium and also have contribution of electron contamination. The detectors used for these measurements should not alter the dose to the target. To counteract these dosimetric problems it is proposed to do the measurements with radiochromic films which are thin detectors and have tissue equivalent properties. MATERIALS AND METHODS: The measurements were done using a Novalis linear accelerator (LINAC) with nominal energy of 6 MV. To determine the surface dose, the total scatter factors (TSF) of three different field sizes were measured in a water phantom at 5 cm depth. Energy dependence of EBT3 was studied at three different depths, using a solid water phantom. The surface measurements were done with the RF for the same field sizes of the TSF measurements. The value of the percentage depth dose was calculated normalizing the doses measured in the RF with the LINAC output, at 5 cm depth, and the TSF. RESULTS: The radiochromic films showed almost energy independence, the differences between the curves are 1.7% and 1.8% for the 1.5 cm and 10 cm depth, respectively. The percentage depth doses values at the surface measured for the 10 cm × 10 cm, 5 cm × 5 cm and 1 cm × 1 cm were 26.1 ± 1.3%, 21.3 ± 2.4% and 20.2 ± 2.6%, respectively. CONCLUSIONS: The RF-EBT3 seems to be a detector suitable for measurements of the dose at the surface. This suggests that RF-EBT3 films might be good candidates as detectors for in vivo dosimetry.

Pancreatic Cancer Incidence, Mortality, and Survival in Puerto Rico, 2001-2015.

OBJECTIVE: To perform an epidemiologic profile of pancreatic cancer (PC) in Puerto Rico (PR) with data gathered from 2001 to 2015. METHODS: Using data from the PR Central Cancer Registry we estimated incidence and mortality rates and trends of PC in PR, and performed survival analyses. We also compared the age-standardized incidence and mortality rates of PC in people in PR with those of Hispanics, non-Hispanic whites, and non Hispanic blacks in the United States (US). RESULTS: From 2011 to 2015, 7.8 per 100,000 persons were diagnosed with PC in PR; higher rates were observed in men than in women (9.2 vs. 6.7 per 100,000, respectively) and in persons 65 years old and older (42.7 per 100,000 persons). For the same period, 6.7 per 100,000 persons died from PC; men and persons 65 years and older had higher mortality rates. Incidence and mortality trends of PC in PR increased from 2001-2015 (annual percent change [APC] = 3.8% and 1.9%, respectively (p<0.05). Lower risk of being diagnosed with and dying from PC was seen in PR than in members of several racial/ethnic groups in the US. The median survival time for PC cases diagnosed in PR during the period of 2008 to 2012 was 5.3 months. CONCLUSION: We observed increasing mortality rates and low survival in PC patients in PR. Research on access and response to treatment is needed to elucidate the reasons for the observed results and have a positive impact on PC burden and survival.

Identification of oestrogen, progesterone receptor and human epidermal growth factor receptor 2 expression in mediastinal metastases of breast cancer obtained by endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: In breast cancer patients, the expression statuses of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are crucial in the choice of treatment. Receptor expression in metastatic lesions can differ from the primary tumour. The aim of our study was to analyse the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to obtain samples allowing the identification of ER, PR and HER2 expression in patients with mediastinal metastases of breast cancer. PATIENTS AND METHODS: The clinical files of all patients with a final diagnosis of breast cancer mediastinal metastases diagnosed by EBUS-TBNA in our institution were retrospectively analysed. The ability of EBUS-TBNA to obtain samples that allowed hormone receptor and HER2 expression analysis was calculated. RESULTS: Twenty-four patients were included. ER, PR and HER2 assessments could be performed in 22, 20 and 22 patients, respectively. In 20 of the 24 patients it was possible to investigate all three types of receptor expression. In the remaining four cases, where ER, PR or HER2 expression tests could not be performed, it was due to a lack of tissue. In cases with adequate results for EBUS-TBNA and the primary tumour agreement was greater for ER (16/19) and HER2 (12/14) than PR (8/17). Based on receptor status, there was a change in the choice of treatment for five patients. CONCLUSION: In patients with breast cancer mediastinal metastases, ER, PR and HER2 expression can be assessed in samples obtained by EBUS-TBNA whenever a sufficient tissue sample is collected.

Identificación de estructuras de infección de Phytophthora palmivora en hojas de clones de palma de aceite Elaeis guinennsis Jacq / Identification of infection structures of Phytophthora palmivora in leaves of oil palm clones Elaeis guineensis Jacq

Este trabajo investigó el modelo de interacción planta-patógeno mediante discos de hojas de clones de palma de aceite inoculados en condiciones ex situ con un aislamiento de Phytophthora palmivora. Las inoculaciones se realizaron en condiciones controladas en cámara de crecimiento. En total, seis diferentes ortets fueron evaluados en seis tiempos de infección (2, 4, 6, 12, 24 y 48 horas postinfección, o hpi). Se determinó la presencia de estructuras de patogenicidad de P. palmivora como quiste, apresorio y tubos germinativos. Los quistes fueron identificados principalmente a las 2, 4 y 6 hpi. A partir de las 48 hpi no hubo presencia de zoosporas enquistadas para ningún ortet evaluado. En cuanto a los apresorios, estos se empezaron a desarrollar a las 4 horas de realizada la inoculación (siendo las 12 y 24 hpi los tiempos de mayor registro de estas estructuras). 121 Identificación de estructuras de infección de Phytophthora palmivora en hojas de clones de palma de aceite (Elaeis guineensis Jacq.) Méndez, K. et al. Introducción La Pudrición del cogollo (pc) es una de las principales enfermedades que afecta al cultivo de palma de aceite, destruyendo plantaciones desde 1964. En Colombia la enfermedad se presenta en las cuatro zonas palmeras y ha alcanzado proporciones epidémicas (Sarria et al., 2013a, 2016). A finales de 2004 en la Zona Suroccidental se registró un incremento en el número de casos, con un crecimiento exponencial de esta enfermedad, y a partir de 2007 se vieron afectadas más de 30.000 ha de cultivos de palma de aceite. En la Zona Central un comportamiento similar de la enfermedad fue registrado para la región de Puerto Wilches (Norte de Santander) entre 2009 y 2013, periodo en el cual se perdieron más de 40.000 ha como consecuencia de una epidemia de pc (Sanz, 2016). Por su parte, los productores de la Zona Norte actualmente hacen frente a la amenaza de una expansión epidémica de la pc con síntoma de hoja clorótica, la cual da cuenta de un estado avanzado de la enfermedad. Una amplia revisión del impacto de esta enfermedad desde sus inicios se encuentra en Benítez & García (2015), Sundram & Intan-Nur (2017) y Torres et al. (2016). La enfermedad de la Pudrición del cogollo es causada por el oomiceto hemibiótrofo P. palmivora (Sarria et al., 2008, 2013). Desde su identificación como agente causal de la pc en 2008, el Centro de Investigación en Palma de Aceite (Cenipalma) ha liderado diferentes investigaciones que han dado como resultado el desarrollo de estrategias de manejo integrado del cultivo de palma, así como la descripción del patógeno por medio de inoculación en condiciones in vitro en foliolos inmaduros de palma (Martínez et al., 2013, 2014a), entre otras. En cuanto a la presencia de esta enfermedad en otros cultivos, Mohamed-Azni et al. (2017) emplearon la técnica de foliolo inmaduro, logrando infectar foliolos de palma de aceite con P. palmivora aislada proveniente de cultivos de cacao y durián. Teniendo en cuenta que actualmente no se conocen fuentes probadas de resistencia de cultivares de Elaeis guineensis a la pc, y que un ciclo de mejoramiento genético de palma puede durar más de 25 años Por su parte, los tubos germinativos se encontraron a partir de las 48 hpi únicamente. Finalmente, se pudo establecer que el patógeno logra colonizar tejidos de foliolo no lignificados de clones de palma. Además, se encontró una relación entre el número de estructuras del patógeno con el comportamiento del cultivar de la palma donor (ramet)

Plant-pathogen model interaction was studied using leaf disks of oil palm clones inoculated ex situ with a Phytophthora palmivora isolate. The inoculation process was performed under growth chamber conditions. Six ortets were evaluated at six post-inoculation times (2, 4, 6, 12, 24 y 48 hours post infection, or hpi). Pathogen's infection structures as cyst, apressorium and germinative tubes were found. Cysts were identified mainly at 2, 4 and 6 hpi. After 48 hpi there were not any cysts for the evaluated ortets. The apresoria started to develop at 4 hpi, with the highest presence of these structures at 12 and 24 hpi. Germinative tubes were found only after 48 hpi. Therefore, it was established that the pathogen can colonize no-lignified tissue of oil palm clones. Finally, we found a relation between the pathogen's structures number and the response of the ortet related to its susceptibility and resistance response. Thus, it was found that the susceptible cultivar showed the highest number of germinative tubes

A549 cells as a model to study endogenous LPA1 receptor signaling and regulation.

Lysophosphatidic acid (LPA) modulates the function of many organs, including the lung. A549 is a lung carcinoma-derived cell line, frequently used as a model for type II pneumocytes. Here we show that these cells expressed messenger RNA coding for LPA1-3 receptors with the following order of abundance: LPA1 > LPA2 > LPA3 and that LPA was able to increase intracellular calcium, extracellular signal-regulated kinases 1/2 phosphorylation, and cell contraction. These effects were blocked by Ki16425, an antagonist selective for LPA1 and LPA3 receptors, and by the LPA1-selective antagonist, AM095. Activation of protein kinase C inhibited LPA-induced intracellular calcium increase. This action was blocked by protein kinase C inhibitors and enzyme down-regulation. Phorbol myristate acetate and AM095, but not Ki16425, decreased the baseline intracellular calcium concentration. Ki16425 blocked the effect of AM095 but not that of phorbol myristate acetate. The data indicate that LPA1 receptors exhibit constitutive activity and that AM095 behaves as an inverse agonist, whereas Ki16425 appears to be a classic antagonist. Furthermore, the LPA agonist, 1-oleoyl-2-O-methyl-rac-glycerophosphothionate, OMPT, induced a weak increase in intracellular calcium, but was able to induce full ERK 1/2 phosphorylation and cell contraction. These effects were blocked by AM095. These data suggest that OMPT is a biased LPA1 agonist. A549 cells express functional LPA1 receptors and seem to be a suitable model to study their signaling and regulation.

Noradrenaline, oxymetazoline and phorbol myristate acetate induce distinct functional actions and phosphorylation patterns of α1A-adrenergic receptors.

In LNCaP cells that stably express α1A-adrenergic receptors, oxymetazoline increased intracellular calcium and receptor phosphorylation, however, this agonist was a weak partial agonist, as compared to noradrenaline, for calcium signaling. Interestingly, oxymetazoline-induced receptor internalization and desensitization displayed greater effects than those induced by noradrenaline. Phorbol myristate acetate induced modest receptor internalization and minimal desensitization. α1A-Adrenergic receptor interaction with ß-arrestins (colocalization/coimmunoprecipitation) was induced by noradrenaline and oxymetazoline and, to a lesser extent, by phorbol myristate acetate. Oxymetazoline was more potent and effective than noradrenaline in inducing ERK 1/2 phosphorylation. Mass spectrometric analysis of immunopurified α1A-adrenergic receptors from cells treated with adrenergic agonists and the phorbol ester clearly showed that phosphorylated residues were present both at the third intracellular loop and at the carboxyl tail. Distinct phosphorylation patterns were observed under the different conditions. The phosphorylated residues were: a) Baseline and all treatments: T233; b) noradrenaline: S220, S227, S229, S246, S250, S389; c) oxymetazoline: S227, S246, S381, T384, S389; and d) phorbol myristate acetate: S246, S250, S258, S351, S352, S401, S402, S407, T411, S413, T451. Our novel data, describing the α1A-AR phosphorylation sites, suggest that the observed different phosphorylation patterns may participate in defining adrenoceptor localization and action, under the different conditions examined.

Antimutagenic and antioxidant activity of the essential oils of Citrus sinensis and Citrus latifolia.

The essential oils of Citrus sinensis and Citrus latifolia showed antimycotic activity against Candida spp. isolated from the oral cavity; they are neither mutagenic on the Ames test nor cytotoxic. Their main components are R-(+)-limonene, ß-thujene, α-myrcene and γ-terpinene. The aim of this work was to evaluate their antimutagenic and antioxidant capacities. Antimutagenic properties were evaluated against MNNG and ENNG on S. typhimurium TA100; against 2AA on strain TA98 and in front of 4NQO and NOR on strain TA102. Both were antimutagenic against MNNG (p < 0.001) but only C. latifolia was antimutagenic against ENNG (p < 0.001). Both presented antimutagenic activity against 2AA (p < 0.001). They were antioxidant against the ROS-generating compound 4NQO (p < 0.001) and the antibiotic NOR (p < 0.001). In the antioxidant evaluation, the activity in DPPH assay was in a range of 6-23% for C. sinensis and of 22-71% for C. latifolia. Both were antioxidant compared with BHT in ß-carotene bleaching assay and were able to decreased apoptosis in HaCat cells stimulated with H2O2. The levels of intracellular superoxide ion were lower in the presence of both oils. In conclusion, the essential oils of C. sinensis and C. latifolia are antimutagenic against at least three types of mutagens and have antioxidants properties.

Sistema de Apoyo para la Cuantificación Semiautomática de Fibrosis Pulmonar en Imágenes de TAC / Support System for Semiautomatic Quantification of Pulmonary Fibrosis in CT Images

Resumen: En este trabajo se presenta un método para calcular los niveles de fibrosis pulmonar en imágenes de tomografía axial computarizada. Se utilizó un algoritmo de segmentación semiautomática basado en el método de Chan-Vese. El método mostró similitudes de forma cualitativa en la región de la fibrosis con respecto al experto clínico. Sin embargo es necesario validar los resultados con una base de datos mayor. El método propuesto aproxima un porcentaje de fibrosis de forma fácil para apoyar su implementación en la práctica clínica minimizando la subjetividad del experto médico y generando una estimación cuantitativa de la región de fibrosis.

Abstract: A method to estimate the pulmonary fibrosis in computed tomography (CT) imaging is presented. A semi-automatic segmentation algorithm based on the Chan-Vese method was used. The proposed method shows a similar fibrosis región with respect to clinical expert. However, the results need to be validated in a bigger data base. The proposed method approximates a fibrosis percentage that allows to achieve this procedure easily in order to support its implementation in the clinical practice minimizing the clinical expert subjectivity and generating a quantitative estimation of fibrosis region.