Análisis estadístico de los espectros de frecuencia de las regiones reguladoras del ENCODE / Statistical analysis of the Fourier Spectra of the ENCODE regulatory regions

RESUMEN En la actualidad, nuevas bases de datos genómicos (secuencias de ADN) son puestas al alcance del dominio público para su análisis. La bioinformática ha desarrollado algoritmos para extraer información y características de dichas secuencias. Sin embargo, estos algoritmos bioinformáticos tienen limitaciones. Una alternativa es utilizar herramientas propias del procesamiento digital de señales (DSP) adaptadas a secuencias genómicas (procesamiento de señales genómicas - GSP). El presente trabajo versa sobre el análisis de los cuatro primeros momentos centrales (media, desviación estándar, asimetría y curtosis) y dos momentos estadísticos (mediana y varianza) de los espectros frecuenciales de las 15 Regiones Reguladoras (RRs) de la base de datos ENCODE con el objetivo de estudiar diferencias estadísticas y frecuencias características. La base de datos seleccionada es "mapeada". Luego, la FFT es calculada a estas señales genómicas y finalmente los momentos estadísticos son implementados. Los resultados mues tran la existencia de 3 grupos de RRs utilizando la media, mediana y curtosis. La desviación estándar y la varianza, parecen no resaltar información importante. Finalmente, la asimetría revela un comportamiento homogéneo ante la presencia de valores atípicos en algunas RRs. Estas observaciones permiten inferir que la periodicidad dentro de la secuencia está relacionada o podría determinar la función biológica que desempeña la misma secuencia.

ABSTRACT Nowadays, new genomic databases (DNA sequences) are available to the whole scientist community for its analysis. The bioinformatics has developed algorithms to extract information and features of the sequences. However, the bioinformatics algorithms have restrictions. An alternative is the use of digital signal processing (DSP) tools adapted to genomic sequences (genomic signal processing - GSP). This work analyzes the first four statistics moments (mean, standard deviation, skewness and kurtosis) and other two moments (median and variance) of the frequency spectra of 15 regulatory regions (RRs) in ENCODE database with the main objective of studying the statistics di fferences and frequency features. The selected database is mapped. Then, the FFT is calculated to these genomic signals and finally the statistic moments implemented. The results show a three-group behavior in the RRs with the mean, median and kurtosis. The deviations standard and the variance do not show important behavior. Finally, the skewness shows a homogeneous behavior with the lack of atypical values in some RRs. These observations support the idea of the presence of periodicities in a sequence that may be related or may determine the biological function that a sequence may perform.

Difficulties in the management of retinal capillary haemangiomas associated with von Hippel Lindau disease. / Dificultades en el manejo de los hemangiomas capilares retinianos asociados a enfermedad de von Hippel-Lindau.

CLINICAL CASE: A 29-year-old female with bilateral retinal capillary haemangiomas (RCH). A genetic analysis was carried out due to the suspicion of von Hippel-Lindau (VHL) disease, with negative results on 2occasions. There was progression of the RCH in the left eye, leading to a macular epiretinal membrane. The patient was treated with laser, intravitreal ranibizumab, and vitrectomy. Finally, a third genetic test detected a de novo mutation in the VHL gene, and led to the genetic diagnosis. DISCUSSION: VHL syndrome causes a complex ocular disease with a difficult diagnosis that requires early treatment of the RCH in order to modify its visual prognosis.

Adaptive pharmacokinetic and pharmacodynamic modelling to predict propofol effect using BIS-guided anesthesia.

BACKGROUND AND OBJECTIVE: Propofol is widely used for hypnosis induction and maintenance of general anesthesia. Its effect can be assessed using the bispectral index (BIS). Many automatic infusion systems are based in pharmacokinetics (PK) and pharmacodynamics (PD) models to predict the response of the patient to the drug. However, all these models do not take into account intra and inter-patient variability. An adjusted intraoperative drug administration allows faster recovery and provides post-operative side-effect mitigation METHODS: BIS evolution and surgery-recorded propofol infusion data of a group of 60 adult patients (30 males/30 females) with ASA I/II physical status were used to test a real time PK/PD compartmental model. This new algorithm tunes three model parameters (ce50, γ and ke0), minimizing a performance function online. RESULTS: The error in the BIS signal predicted by the real time PK/PD model was smaller than the error measured with fixed parameter equations. This model shows that ce50, γ and ke0 change with time and patients, given a mean (95% confidence interval) of 3.89 (3.52-4.26)mg/l, 4.63 (4.13-5.13) and 0.36 (0.31-0.4)min(-1), respectively. CONCLUSIONS: The real time PK/PD model proposed provides a closer description of the patient real state at each sample time. This allows for greater control of the drug infusion, and thus the quantity of drug administered can be titrated to achieve the desired effect for the desired duration, and reduce unnecessary waste or post-operative effects.

Francisella sp., an emerging pathogen of tilapia, Oreochromis niloticus (L.), in Costa Rica.

Francisella sp. is an emergent bacterial pathogen that causes acute to chronic disease in warm and cold water cultured and wild fish species. During the past 3 years, the bacterium has been detected in tilapia, Oreochromis niloticus, cultured in Costa Rica. Infected fish presented non-specific clinical signs, such as erratic swimming, anorexia, anaemia, exophthalmia and high mortality. Upon macroscopic and microscopic examination, several internal organs (mainly spleen and kidney) were enlarged and contained white nodules. Histological examination revealed the presence of multifocal granulomatous lesions, with the presence of numerous small, pleomorphic, cocco-bacilli. The bacteria were isolated from infected tilapia on selective media and grown on several media with and without antibiotics. Specific PCR primers to the Francisella genus were used to confirm the preliminary diagnoses. In comparison with several bacterial 16S rRNA sequences, our isolate was found to share 99% identity with other Fransicella spp. isolated from fish, and more than 97% identity to the human pathogen Francisella tularensis. Koch's postulates were fulfilled after experimental intraperitoneal and gill exposure challenges.

Isolation of Toxoplasma gondii from the keel-billed toucan (Ramphastos sulfuratus) from Costa Rica.

Pectoral muscles from a captive keel-billed toucan (Ramphastos sulfuratus) from Costa Rica were fed to a Toxoplasma gondii-free cat, and the cat shed oocysts. Laboratory mice fed these oocysts developed antibodies to T. gondii in their sera and T. gondii tissue cysts in their brains. The DNA extracted from the brains of infected mice was characterized using 10 polymerase chain reaction-restricted fragment length polymorphic markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico). The isolate designated TgRsCrl was found to be non-clonal with Type I, II, and III alleles at different loci. This is the first isolation of T. gondii from this host.

Low frequency of human papillomavirus DNA in breast cancer tissue.

Human papillomavirus (HPV) is considered the aetiological agent for cervical cancer. Several reports have addressed a relationship with HPV and breast cancer, as different HPVs have been identified. The purpose of this study was to detect HPV DNA in 67 breast cancer patients and 40 non-malignant disease breast tissues by means of Polymerase Chain Reaction with consensus primers. The frequency of HPV in the cases group were 4.4% (3/67) and no positive samples among the reference group were identified. From the 3 positive samples, HPV types 16, 18 and 33 were identified by restriction patterns and direct sequencing. The high diversity among detection in the related studies shows that population genomic heterogeneity plays an important role in the disease. The low frequency detected in the present study suggests that HPV does not play an important role in breast cancer.

Mast cell tumour in a giant Galapagos tortoise (Geochelone nigra vicina).

A well-differentiated cutaneous mast cell tumour was diagnosed in a subadult female giant Galapagos tortoise. The tumour was a pedunculated, verrucose mass located near the base of the neck. The histological features, which were diagnostic for a mast cell tumour, included abundant intracytoplasmic granules that were stained metachromatically with Giemsa and toluidine blue stains. Mast cell tumours are rare in reptiles, and this is the first description of a mast cell tumour in a chelonian.

Spirorchiidiosis (Digenea: Spirorchiidae) and lesions associated with parasites in Caribbean green turtles (Chelonia mydas).

Forty-seven nesting green turtles (Chelonia mydas) were examined for parasitic pathogens. Four species of cardiovascular flukes (Digenea: Spirorchiidae), Learedius learedi, Hapalotrema postorchis, Monticellius indicum and Amphiorchis solus were collected from 39 of 40 of the turtles, and Neospirorchis species were identified in seven of the 47 by histological examination. The pathological changes associated with the spirorchiids and their eggs included aneurysms, arteritis of great vessels with dark nodular thickenings, endocarditis, haemorrhagic lesions, thrombi, vasculitis, and granulomatous reactions in all the turtles. Ozobranchus branchiatus (Hirudinea: Ozobranchidae) leeches were found on the skin of 27 of the 47 turtles and were associated with traumatic purulent and ulcerative dermatitis. Oesophagitis associated with Rameshwarotrema uterocrescens (Digenea: Pronocephalidae) was recorded in 11 of 43 of the turtles. Petechial haemorrhages and unspecific crater-like ulcerated lesions on the gastric mucosa associated with Charaxicephaloides species and Charaxicephalus robustus (Digenea: Pronocephalidae) were observed in four of 40 of the turtles. Cholycystitis and ectasia of mucosal glands associated with Rhytidodoides similis (Digenea: Rhytidodidae) were observed in one of the 47 turtles. Fibropapillomas were observed on the skin of one turtle and fibromas on the skin of two of them.

HLA class II genotypes in Mexican Mestizo patients with myasthenia gravis.

Myasthenia gravis is an autoimmune, heterogeneous disorder, characterized by the presence of antibodies against acetylcholine receptors at the neuromuscular junction. There is a strong evidence that an individual's genetic composition is an important predisposing factor for the development of the disease. To correlate HLA class II genotypes with thymic pathology in Mexican Mestizo patients who had been subjected to thymectomy. HLA class II genes were analyzed in 60 patients and in 99 healthy ethnically matched controls. Thymic hyperplasia, atrophy, thymoma, and normal histology were encountered in 56, 33, 8 and 2% of patients, respectively. HLA-DR11 was significantly increased in patients with thymoma compared with healthy controls (pC = 0.001, OR = 13.35, 95% CI 3.5-51.3), compared with the subgroup of hyperplasia patients (pC = 0.005, OR = 15.5, 95% CI 2.78-95.58) and with the atrophy subgroup (pC = 0.04, OR = 10.5, 95% CI 1.75-70.95). This study provides the evidence of an association between HLA class II alleles with clinical and genetic heterogeneity in myasthenia gravis, particularly in those with thymoma (HLA-DR11).

Severe community-acquired pneumonia and sepsis caused by Burkholderia pseudomallei associated with flooding in Puerto Rico

Burkholderia pseudomallei (melioidosis) is usually found in endemic areas of Southeast Asia and Northern Australia. However, a few cases of confirmed melioidosis indigenous to Puerto Rico and the Americas have been reported previously. We describe the occurrence of a B. pseudomallei infection in a female with insulin-dependent diabetes mellitus exposed to flood waters in Puerto Rico. We conclude that B. pseudomallei should be considered a potential pathogen in high-risk patients with severe community-acquired pneumonia and sepsis in Puerto Rico especially in individuals exposed to flood waters during rainy seasons. A more thorough epidemiologic and microbiologic surveillance with environmental sampling may be warranted in the island

LMP2 and LMP7 gene polymorphism in Mexican populations: Mestizos and Amerindians.

Low molecular weight polypeptide (LMP) genes are located within the major histocompatibility complex and have been associated with autoimmune diseases such as ankylosing spondylitis. In order to define the distribution of LMP genes in Mexican populations, the LMP2 and LMP7 polymorphism was analyzed in 312 Mexican individuals (95 Mexican Mestizos, 48 Nahuas, 56 Mazatecans, 50 Teenek, and 63 Mayos) belonging to different ethnic groups. In Mexican populations both Mestizos and Amerindians presented similar distribution of LMP2 and LMP7 polymorphisms, except Nahuas and Mayos who presented the higher frequencies of LMP2-H/H and the lowest frequencies of LMP2-H/R genotypes (P < 0.05 when compared with Mexican Mestizos). The LMP7-K/K genotype was absent in Nahuas, Teenek and Mayos and only one Mazatecan individual presented this genotype. Differences with other populations were found in Mexicans. An increased frequency of LMP2-H and a decreased frequency of LMP2-R alleles were observed in Mexican Amerindians (Nahuas and Mayos) when compared with Brazilian Amerindians (Kaingang and Guarani) and Caucasians (Spaniards) (P < 0.05). All Mexican populations (Mestizos and Amerindians) presented an increased frequency of LMP7-Q allele and a decreased frequency of LMP7-K allele when compared to Brazilian Amerindians (Kaingang), Caucasians (United States) and Asian (Japan) populations (P < 0.05). Genetic distances showed that Mexican Mestizos have an important relation with Spaniards and with all Mexican Amerindians. The present data corroborate the influence of Spaniard and Amerindian genes in the Mexican Mestizo population and could help to define the true significance of LMP polymorphism as genetic and evolutive marker in the Amerindian populations.

Interleukin-1beta-induced nitric oxide production in rat aortic endothelial cells: inhibition by estradiol in normal and high glucose cultures.

Expression of inducible nitric oxide synthase (iNOS) and the resultant increased nitric oxide (NO) production are associated with septic shock, atherosclerosis, and cytokine-induced vascular injury. Estrogen is known to impact vascular injury and vascular tone, in part through regulation of NO production. In the current study, we examined the effect of physiological concentrations of estradiol on interleukin-1beta (IL-1beta)-induced NO production in rat aortic endothelial cells (RAECs). 17Beta-estradiol significantly decreased IL-1beta-induced iNOS protein levels and reduced NO production in RAECs. High glucose (25 mM) elevated the increase in IL-1beta-induced iNOS protein and NO production. Nevertheless, estradiol still inhibited IL-1beta-induced iNOS and NO production even in the presence of high glucose. These data suggest that estradiol may exert its beneficial effects in part by inhibiting induction of endothelial iNOS, a possible mechanism for the protective effect of estradiol against diabetes-associated cardiovascular complications.

[Ketamine]. / Ketamina.

Ketamine is an intravenous drug with special properties that make it the only agent that presently serves as anesthetic, sedative, amnesiac and analgesic. Although it is sometimes forgotten, ketamine is still considered a viable drug. Water soluble, stable and non-irritant when administered intravenously, ketamine has rapid onset after intravenous injection and provides acceptable anesthesia when administered in continuous infusion. There properties make ketamine useful for total intravenous anesthesia. Both propofol and midazolam are effective in reducing ketamine's adverse side effects. Administered in children by oral, nasal, rectal and intramuscular routes, ketamine allows for gentle anesthetic induction. It can also serve as an adjuvant in regional anesthesia to supplement analgesia. In adults ketamine is most often used for major surgery, particularly in the elderly or in high risk patients who are in shock, severely dehydrated or hemodynamically unstable, or in obstetric patients with hypovolemia or hemorrhage. It is probably the anesthetic of choice for patients with hyperreactive airways. Ketamine's strong analgesic effect at subanesthetic doses allows it to be used as an analgesic during postoperative intensive care or as an analgesic-plus-sedative for patients receiving mechanical ventilation. Interest in using ketamine at low doses for cancer and non-cancer patients with chronic pain has grown recently.

Neosporosis-associated abortion in a dairy goat.

Neospora canium tachyzoites and tissue cysts were found in tissues of a goat fetus aborted after 3.5 months of gestation. The fetus had hydrocephalus and a hypoplastic cerebellum. The predominant lesion in the fetus was severe encephalitis associated with numerous N canium tissue cysts. Parasites in fetal tissues reacted positively with N caninum antibodies in immunohistochemical tests. The doe was clinically normal and had a 1:800 antibody titer to N caninum as determined by use of an indirect fluorescent antibody test 9 months after abortion. Five of 77 other does from this herd also had indirect fluorescent antbody titers to N caninum that were > or = 1:100.

[Patient with tricuspid atresia undergoing orthopedic surgery: anesthetic considerations]. / Paciente con atresia tricúspide para cirugía ortopédica: cuidados anestésicos.

We describe a 52-year-old patient with rheumatoid arthritis, interventricular communication and pulmonary stenosis. After an accidental fall she was scheduled for total hip replacement. The main objective of anesthetic management was to preserve pulmonary blood circulation at arterial pressures that would assure adequate tissue perfusion. Other objectives were to maintain hydration to prevent decreases in hematocrit levels, avoid systemic embolization and allow for antibiotic prophylaxis.

[Colorectal cancer in the context of multiple primary malignant neoplasms]. / El cáncer colorrectal en el contexto de las neoplasias primarias malignas múltiples.

INTRODUCTION: The finding of more than one carcinoma throughout the life of a patient is not unusual. In fact, the occurrence of multiple primary cancers has been well documented. However, the features, implications and prognosis of colorectal cancers associated to other malignancies, have been less well documented. PATIENTS AND METHOD: We report 29 patients with multiple primary neoplasms in which at least one of them was a colorectal cancer. Number, extension and localization of colonic neoplasm, and time interval between diagnosis of both neoplasms, and mortality and survival rate were retrospectively analyzed. Follow-up ranged from 1 to 360 months. RESULTS: Twenty three patients had two cancers, and six more than three neoplasms. Colorectal cancer was primary in 8 patients, metachronous in 14 patients and synchronous in 5 patients. Breast (7 cases), prostate (5 cases), endometrium (3 patients) and stomach (3 cases), were the other malignancies most frequently detected. Overall, 13 of the 27 patients (49%) died during the follow-up period after the recognition of the colorectal cancer. Two patients were lost to follow-up. Mantel-Haenszel test did not show significative differences in survival between patients with two or more neoplasms. There were no differences in survival depending upon the timing of diagnosis of the colorectal tumor. CONCLUSIONS: These data suggest that colorectal cancer may share etiologic factors with hormone-dependent neoplasms (breast, prostate) and gastric cancer. In patients with primary multiple neoplasms, the number of neoplasms detected and the interval time between both diagnosis are not prognostic factors when one of the malignancies in colorectal cancer.

He-Ne laser has no effect on cell cycle phases of human colon adenocarcinoma cells.

The aim of this study is to investigate the effect of He-Ne continuous laser (12.6 mW, 632.8 nm), at low energy densities, on cell cycle synchronization of monolayer growing human colon adenocarcinoma cell line. The doubling time of cell culture was used as optimum time to verify laser effect. The monolayer cultures were exposed to single doses of different energy densities (0.042 J cm-2 to 1.68 J cm-2). The nuclear DNA content has been studied by flow cytometry to obtain the cell percentage in each cell cycle phase. Results show no effect of He-Ne laser irradiation on cell cycle short time synchronization under the previously mentioned conditions and cell type. Higher energy densities and multiple irradiations should be investigated.

Optical quality of the eye lens surfaces from roughness and diffusion measurements.

The Purkinje-Sanson images and the image of the anterior lens surface, formed by coherent light, are studied in this paper. The roughness and the diffusing behavior of the anterior lens surface are studied by two complementary methods: measurement of the scattering halo in the third Purkinje image and speckle-contrast measurements in the image of the anterior surface (lens epithelium). The scattering properties of the anterior lens surface are represented by an equivalent Gaussian diffusing surface defined by the standard deviation of the surface height, sigma h = 0.143 micron, and the correlation length, r0 = 7 microns. The relative contribution of this surface to the intraocular scattering has been evaluated, and it depends strongly on the age of the subjects.