Vitamin D receptor (VDR) expression in different molecular subtypes of canine mammary carcinoma.

BACKGROUND: The molecular-based classification of canine mammary carcinomas (CMCs) has been the focus of much current research. Both in canines and humans, the triple-negative (TN) molecular subtype of mammary cancer is defined by a lack of expression of progesterone receptor (PR), oestrogen receptor (ER) and HER2. It has a poor prognosis; no effective targeted therapy is available. Vitamin D displays anticarcinogenic properties, and the expression of its receptor (VDR) has been found in different molecular subtypes, being about 30-40 % of TN breast cancer (TNBC) positive to it. We assessed the VDR expression in the different molecular subtypes of 58 CMCs from 45 female dogs using an immunohistochemical panel for the molecular classification of included: PR, ER, HER2, cytokeratin (CK) 5, CK14, and Ki67. In addition, we studied the relationship among the molecular subtypes of CMCs and clinicopathologic parameters. RESULTS: Investigation showed VDR positivity in 45.0 % of the triple-negative CMCs (TNCMCs), 27.3 % of luminal B and 19.0 % of luminal A. Luminal A was the most molecular subtype represented of the total tumours (36.2 %), followed of TNCMCs (34.5 %), luminal B (20.7 %) and HER2-overexpression (10.3 %). Both HER2-overexpression and TNCMC subtypes were positively related to lymphatic invasion (P = 0.028), simple histologic subtype (P = 0.007), a higher histological grade (P = 0.045) and a trend to higher proliferation index (P = 0.09). CONCLUSIONS: The highest VDR expression was observed in TNCMC, being almost half of them (45 %) positive to this receptor. VDR expression was absent in HER2-overexpression tumours and low in luminal A and B molecular subtypes.

Multifractal structure of the monthly rainfall regime in Catalonia (NE Spain): Evaluation of the non-linear structural complexity.

The complex non-linear regime of the monthly rainfall in Catalonia (NE Spain) is analyzed by means of the reconstruction fractal theorem and the multifractal detrended fluctuation analysis algorithm. Areas with a notable degree of complex physical mechanisms are detected by using the concepts of persistence (Hurst exponent), complexity (embedding dimension), predictive uncertainty (Lyapunov exponents), loss of memory of the mechanism (Kolmogorov exponent), and the set of multifractal parameters (Hölder exponents, spectral asymmetry, spectral width, and complexity index). Besides these analyses permitting a detailed description of monthly rainfall pattern characteristics, the obtained results should also be relevant for new research studies concerning monthly amounts forecasting at a monthly scale. On one hand, the number of necessary monthly data for autoregressive processes could change with the complexity of the multifractal structure of the monthly rainfall regime. On the other hand, the discrepancies between real monthly amounts and those generated by some autoregressive algorithms could be related to some parameters of the reconstruction fractal theorem, such as the Lyapunov and Kolmogorov exponents.

Influence of exposure to tobacco cigarette smoke on the eosinophil count in the nasal mucosa of young patients with perennial allergic rhinitis.

BACKGROUND: To assess the influence of exposure to tobacco cigarette smoke on the eosinophil count and the frequency of apoptosis of eosinophils in the nasal mucosa of teenagers with perennial allergic rhinitis. METHODS: Fifty patients were evaluated (aged 10 to 19 years old): 25 patients with and 25 patients with no recent exposure to tobacco cigarette smoke, by means of The Global Youth Tobacco Survey and cotinine/creatinine ratio. After a clinical evaluation, all the patients replied to a validated questionnaire of the severity of nasal symptoms; then, a nasal sample was processed to identify the eosinophil count and the frequency of apoptosis of eosinophils. RESULTS: Patients with active exposure to tobacco cigarette smoke had higher eosinophil counts than patients with no exposure to the smoke. In the two groups, apoptosis of eosinophils in the nasal mucosa was scarce and no significant correlation was observed between the frequency/severity of the nasal symptoms and the eosinophil count. CONCLUSION: Teenagers with perennial allergic rhinitis and active exposure to tobacco cigarette smoke may show increased eosinophil counts in the nasal mucosa, which might not be related to apoptosis of eosinophils or to the frequency/severity of nasal symptoms.

Rhinomanometry in young patients with perennial allergic rhinitis with/without recent exposure to tobacco smoke.

OBJECTIVE: To assess the influence of environmental exposure to tobacco smoke on the nasal symptoms and nasal resistance of young patients with perennial allergic rhinitis. DESIGN: Cross-sectional study. SETTING: Tertiary referral centre. PARTICIPANTS: Fifty patients were evaluated (aged 10-19 years old): 25 patients with and 25 patients without recent exposure to tobacco smoke (confirmed by cotinine/creatinine ratio). MAIN OUTCOMES MEASURES: After a clinical evaluation, all the patients replied to a validated questionnaire of the severity of the nasal symptoms. Then total nasal airway resistance was recorded by active anterior rhinomanometry. RESULTS: Patients with exposure to tobacco smoke had a larger total resistance than patients without exposure (t-test, P < 0.01). No significant correlation was observed between the total score of the questionnaire of nasal symptoms and the nasal resistance. CONCLUSIONS: In young patients with perennial allergic rhinitis, exposure to tobacco smoke can be related to increased nasal resistance, which may not be recognised by the report of nasal symptoms.

[Predictive models of gestational diabetes, a new prediction mode]. / Modelos predictivos de diabetes gestacional, un nuevo modelo de predicción.

OBJECTIVES: Recognized the value of gestational diabetes (GD) as a health problem, our aim in this work has been to analyze the diagnostic performance of the different today's existing criteria (GEDE, O'Sullivan and Carpenter) after the overload of 100 g of glucose and revise how to increase its efficiency. MATERIALS AND METHODS: We carried out a description of all the variables. In the analytical phase of the work, we used Pearson's Chi square to see if there were differences in the percentage of cases collected in each health center and the proportions contrast test to study the differences between the experimental prevalence. We completed binary logistic regression models using as result variable having or not having gestational diabetes (yes/no) and as predictors the four measurements of the curve with 100 g of glucose overload. To decide which model was better, the stepwise backward-forward analysis and the surface of the ROC curve generated by each of them were considered. RESULTS: We obtained a sample of 170 pregnant women from six different Primary Care Area of Seville health centers who had shown a positive O'Sullivan test with a median age of 35 years. There were significant differences in the prevalence proportions according to the criteria used: GEDE/O'Sullivan p < 0.001; GEDE/Carpenter p < 0.001. Logistic models with three and four predictor variables were equal in discriminatory diagnostic capacity when the GEDE criteria were used (area under the ROC curve = 0.96, 95% CI: 0.93-0.98). The back-forward stepwise analysis stayed with the three-variable model as the most parsimonious. The same did not occur when applying the other two criteria. CONCLUSIONS: Regarding an observational design, we state that there are significant differences in the prevalence proportions observed according to the criteria applied (p < 0.001) and we can also support that using the GEDE criteria, the taking of the third hour could be dispensed with, based on Bayesian criteria and the application of the ROC curve analysis.

[Giant colonic diverticulum. Report of a case and review of the literature]. / Divertículo colónico gigante. Informe de un caso y revisión de la bibliografía.

We report about a 67 year-old male patient with a giant colonic diverticulum and multiple comorbid conditions. The unusual clinical presentation and high surgical risk in this case required challenging therapeutic decisions that eventually lead to a left colon resection and complementary surgical procedures, despite the patient had been considered non-surgical candidate by two surgical teams before. A literature review from the last ten years was performed using Medline and Pubmed databases, looking for "giant colonic diverticulum". We found 43 case reports, one case series and one review article including 135 patients. Discussion is based on the information obtained from the literature review and the particular aspects of this interesting case.

Dyslipidaemia and other cardiovascular risk factors in relation to manifest cardiovascular disease in patients with chronic obstructive pulmonary disease in the Canary Islands. / Relación entre la dislipidemia y otros factores de riesgo cardiovasculares conocidos con la presencia de enfermedad cardiovascular en pacientes con enfermedad pulmonar obstructiva crónica de las Islas Canarias.

INTRODUCTION: Cardiovascular disease has a negative impact on the vital prognosis of patients with chronic obstructive pulmonary disease (COPD), where dyslipidaemia (DLP) and arterial hypertension (AHT) are considered the most prevalent risk factors. The objective of this study was 1) to assess the relationship between diagnosed DLP and cardiovascular disease in COPD patients and compare it with other known cardiovascular risk factors and 2) to determine the relationship between the different cardiovascular comorbidities and the severity groups according to the GOLD 2017 classification. METHODS: A cross-sectional, observational study was performed in 454 outpatients with COPD during their follow up. We calculated the prevalence of each of the cardiovascular comorbidities and the probability of each of the cardiovascular risk factors to occur jointly with a vascular disease (RRij). RESULTS: A total of 66.7% of the patients had DLP, whereby DLP was related to cerebrovascular accidents (CVA) (RRij 1.36, P=.0054), chronic kidney disease (CKD) (RRij 1.34, P=.00023), and peripheral arterial disease (PAD) (RRij 1.38, P=.00015). AHT was mostly related to CVA (RRij 1.41, P=.0014) and CKD (RRij 1.42, P<.0001). Type 2 diabetes mellitus (T2DM) correlated with PAD (RRij 1.90, P=.0001), heart failure (HF) (RRij 1,74, P=.0002), and CKD (RRij 1.76, P<.0001), and obesity was associated with HF (RRij 1.60, P=.0009) and CKD (RRij 1.54, P=.0001). CONCLUSION: DLP was related to CVA, CKD, and PAD. AHT and T2DM are the conditions that mostly relate to HF and CVA.

[Preoperative workup to assess indication for laparoscopic treatment in gastroesophageal reflux disease].

INTRODUCTION AND OBJECTIVES: antireflux surgery performed by an experienced surgeon is a maintenance option for patients with well-documented gastroesophageal reflux disease (GERD). Well-documented GERD is difficult to find, as GERD is a multifactorial disease in which the gastroesophageal junction, with its special anatomical and functional components, is important. In order to examine patient preoperative workups, and their indication for surgical treatment in GERD, we retrospectively studied patients who underwent a laparoscopic antireflux procedure. METHODS: preoperative workups in patients from our health care area who underwent a laparoscopic antireflux procedure from December 1997 to February 2007 were retrospectively analyzed. Data related to epidemiological findings, symptoms, morphologic and functional evaluation, medical therapy, and indication for surgical treatment were recorded and statistically analyzed by means of a bivariate test. Differences were significant when the p value was equal to or less than 0.05. RESULTS: 100 patients (50 % female, 51.31 +/- 13.53 years of age) underwent a laparoscopic antireflux surgery after 56.47 +/- 61.33 months with symptoms. Ninety-five percent of patients had an anatomical abnormality. The pH monitoring test diagnosed three quarters of cases. The most frequent indication for GERD treatment was persistent or recurrent esophagitis despite adequate medical treatment (52 cases). CONCLUSIONS: based on our preoperative workup, as described, 100 percent of subjects were well documented and diagnosed with GERD (both non-erosive reflux disease and erosive reflux disease), and their indication for laparoscopic treatment was retrospectively assessed in 94% of cases.

[Malignant fibrous histiocytoma of the spermatic cord. Presentation of one case and literature revision]. / Histiocitoma fibroso maligno de cordón espermático. Presentación de un caso y revisión de la literatura.

We present a case of malignant fibrous histiocytoma (MFH) of the spermatic cord. An 80-years-old man was admitted to the hospital with a left scrotal mass, related to a genital traumatism several months ago. Under the suspicion of a testicular tumor, left radical orchiectomy was performed. Histological examination of the tumoral mass revealed a malignant fibrous histiocytoma. The tumor was firmly adhered to the spermatic cord. MFH is an extremely rare, highly malignant connective tissue tumor, which may, occasionally, affect the male genital tract. There are no agreed treatment principles. The overall prognosis is poor.

Reference genes for RT-qPCR normalisation in different tissues, developmental stages and stress conditions of amaranth.

Studies of gene expression are very important for the identification of genes that participate in different biological processes. Currently, reverse transcription quantitative real-time PCR (RT-qPCR) is a high-throughput, sensitive and widely used method for gene expression analysis. Nevertheless, RT-qPCR requires precise normalisation of data to avoid the misinterpretation of experimental data. In this sense, the selection of reference genes is critical for gene expression analysis. At this time, several studies focus on the selection of reference genes in several species. However, the identification and validation of reference genes for the normalisation of RT-qPCR have not been described in amaranth. A set of seven housekeeping genes were analysed using RT-qPCR, to determine the most stable reference genes in amaranth for normalisation of gene expression analysis. Transcript stability and gene expression level of candidate reference genes were analysed in different tissues, at different developmental stages and under different types of stress. The data were compared using the geNorm, NormFinder and Bestkeeper statistical methods. The reference genes optimum for normalisation of data varied with respect to treatment. The results indicate that AhyMDH, AhyGAPDH, AhyEF-1α and AhyACT would be optimum for accurate normalisation of experimental data, when all treatment are analysed in the same experiment. This study presents the most stable reference genes for normalisation of gene expression analysis in amaranth, which will contribute significantly to future gene studies of this species.

Vitamin D receptor expression in canine mammary gland and relationship with clinicopathological parameters and progesterone/oestrogen receptors.

The vitamin D receptor (VDR) belongs to the nuclear class II receptor family. VDR is a ligand transcription factor and mediates the actions of calcitriol, the active product of vitamin D synthesis. Nowadays, it is known that the biological actions of calcitriol include the capacity to modulate cancer features, such as proliferation and differentiation, apoptosis, angiogenesis, invasion and metastasis. VDR expression has been demonstrated in human breast cancer and vitamin D has emerged as a promising targeted therapy. We analyse the VDR expression in normal and neoplastic canine mammary tissue samples and its relationship with clinicopathological parameters and progesterone/oestrogens receptors (PR/ER). Expression of VDR, Ki67 (to evaluate the proliferation index, PI), PR and ER was assessed in 50 mammary gland tissue samples from 41 female dogs by immunohistochemistry. VDR-positive staining was found in the nuclei of both myoepithelial and luminal epithelial cell layers. VDR expression was higher in normal mammary tissue (37/37 cases, 100%) then followed by benign tumours (6/15 cases, 40%) and malignant tumours (9/34 cases, 26.5%) (P = .001). Female dogs aged ≥10 years had lower VDR expression compared with dogs younger (P = .017). Relationship between VDR and breed, number of tumours, tumour size, histologic subtype, histologic grade of malignancy, PI and PR and ER expression was not observed. Studies with more samples are necessary to further evaluate the possible role of VDR in the biological behaviour of canine mammary tumours, and to corroborate the possibility to use the dog as model for human breast cancer.

[Resistance rates and phenotypic characterization of Streptococcus pyogenes in a paediatric population in Northern Spain (2005-2015)]. / Cambios evolutivos en las tasas y fenotipos de resistencia de Streptococcus pyogenes en una población pediátrica de Asturias, España (2005-2015).

OBJECTIVE: Streptococcus pyogenes is a significant cause of bacterial infections in children. The aim of the study is to analyse resistance rates and phenotypes of S. pyogenes isolates in a paediatric population in Northern Spain over the last 11 years. METHODS: Descriptive retrospective study of S. pyogenes isolates from paediatric patients between 2005 and 2015 in a region of Asturias (Spain). Resistance rates and changes in erythromycin resistance phenotypes in two time periods (2005-2009 and 2010-2015) were studied. RESULTS: A total of 1,794 S. pyogenes isolates were registered (70% from 2005 to 2009). 87.5% were obtained from pharyngeal swabs and 0.2% from blood cultures. Resistance rates to tetracycline (8.8% to 4.3%, p=0.02), erythromycin (22% to 9.3%, p<0.01) and clindamycin (6% to 1.7%, p<0.01) decreased between the two study periods. A reduction in erythromycin-resistant isolates with the MLSB phenotype was observed. CONCLUSIONS: A decrease in S. pyogenes resistance rates to erythromycin and clindamycin and a change in the erythromycin resistance phenotype were observed along the study period.

[Diagnosis and treatment of urological complications in kidney transplants]. / Diagnóstico y tratamiento de las complicaciones uroógicas del trasplante renal.

OBJECTIVE: To analyze the incidence of urological complications, like fistula and stenosis in our series of 282 renal transplants and their management. MATERIALS AND METHODS: Between December 1995 and October 2005, 282 adult recipients underwent renal transplant. The most common urological complication was urinary fistula. This complication was observed in 24 cases (8.5%), ureteral stenosis in 18 cases (6.4%) and both of them in 5 (1.7%). The items recorded on these patients included the time to diagnosis, the image technique, the type of ureteral stents and the clinical evolution. RESULTS: Endourologic treatment with percutaneos nefrostomy, double-J catheter and metalic endoprotesis was performed successfully in 76.4% of urinary fistula, in 66.7% of ureteral obstruction and in 60% of patients who developed both of them. CONCLUSION: Endourologic procedures have replaced open reconstructive surgery in most patients with ureteral obstruction or urinary fistula after renal transplant, because they may offer a definitive treatment with low morbidity.

Is time to search the Wells Score 4.0? / ¿Ha llegado el momento de buscar la escala de Wells 4.0?

BACKGROUND: Wells score for deep vein thrombosis presents problems for implementation in the hospital emergencies, mainly due to the complexity of its enforcement. OBJECTIVE: To assess whether the inclusion of D-dimer as a predictor might lead to a simplification of this clinical decision rule. PATIENTS AND METHODS: A database of deep vein thrombosis patients was studied by logistic regression model in which the 10 predictors in the Wells score and the dimer D were included. The diagnosis was made with compression ultrasonography with Doppler signal. D-dimer was determined by a quantitative method of latex, a technique immunofiltration or a turbidimetric technique. RESULTS: 577 patients (54.1% women) were studied, with a mean age of 66.7 (14.2) years. 25.1% were diagnosed with deep vein thrombosis. Only four variables were independent, building a weighted model with greater predictive ability (area under the curve) than the original model (0.844 vs. 0.751, p<0.001). Both models showed an acceptable safety, with a similar rate of failure (0.8% vs. 1%). The simplified model allowed to select a higher percentage of patients who could have benefited from the non performance of the imaging test (20.6% vs. 15.8%, p=0.039). CONCLUSIONS: The introduction of D-dimer in a regression model simplifies the Wells score and maintain the same efficacy and safety, which could improve its implementation in the hospital emergencies.

Activation of c-fos expression in hypothalamic nuclei by mu- and kappa-receptor agonists: correlation with catecholaminergic activity in the hypothalamic paraventricular nucleus.

Administration of the preferential mu-opioid receptor agonist, morphine, and selective K-opioid receptor agonists elicits activation of the hypothalamus-pituitary-adrenocortical axis, although the site or the molecular mechanisms for these effects have not been determined. The expression ofFos, the protein product of the c-fos protooncogene, has been widely used as an anatomical marker of monitoring neuronal activity. In the present study we evaluated 1) the effects of the mu-opioid receptor agonist, morphine, and those of the selective K-opioid receptor agonist, trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl-]benzeneacet amide methane sulfonate (U-50,488H), administration on the expression of Fos in hypothalamic nuclei; and 2) the possible modification of the activity of noradrenergic neurons known to send afferent projections to the paraventricular nucleus (PVN), the site of CRF neurons involved in initiating ACTH secretion. Using immunohistochemical staining of Fos, the present results indicate that acute treatment with either morphine or U-50,488H induces marked Fos immunoreactivity within the hypothalamus, including the medial parvicellular PVN and supraoptic and suprachiasmatic nuclei. Pretreatment with naloxone attenuated the effect of morphine, whereas nor-binaltorphimine, a selective kappa-opioid receptor antagonist, abolished the effect of U-50,488H on Fos induction. Correspondingly, morphine and U-50,488H injection increased the production of the cerebral noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol as well as noradrenaline turnover in the PVN. These effects were antagonized by naloxone and nor-bin-altorphimine, respectively. All of these findings are discussed in terms of specific events that couple opioid-induced activation of the hypothalamus-pituitary-adrenocortical axis and noradrenergic activity with changes in gene expression in selective hypothalamic nuclei.

Scorpion envenoming in two regions of Colombia: clinical, epidemiological and therapeutic aspects.

To determine clinical and epidemiological features of scorpion stings in two departments of Colombia, a descriptive study was performed in the hospitals of 10 towns from Antioquia (2 256 071 inhabitants) and five from Tolima (630 424 inhabitants). One hundred and twenty-nine cases were admitted during one year, 51 in Antioquia, 78 in Tolima and 41 were children less than 15 years old. Most stings (70.5%) occurred inside the house; 27.9% were on the hands and 26.4% on the feet. The scorpion species involved were Tityus pachyurus (51), Centruroides gracilis (31), T. fuehrmanni (29), T. asthenes (7) and Chactas spp. (1). In 10 cases the scorpion involved was not identified. Systemic envenoming signs (e.g. vomiting, tachypnea) were significantly more frequent in children than in adults (P < 0.05). Four children had hypertension, but none developed pulmonary oedema. One 3-year-old girl, stung by T. asthenes, had acute oedematous pancreatitis. Ninety-eight patients had mild envenoming. Moderate (27 patients) and severe (four patients) envenoming was significantly more frequent in children than in adults (P = 0.003; relative risk = 2.97). A pepsin-digested anti-Centruroides spp. antivenom was administered to 19 of 31 patients presenting systemic envenoming signs. No adverse reactions to antivenom were observed.