Evaluation of teratogenicity and genotoxicity induced by kramecyne (KACY).

Kramecyne (KACY), a polymer isolated from Krameria cytisoides Cav, has anti-inflammatory, anti-nociceptive, anti-arthritic and anti-ulcerogenic properties. As a part of standard preclinical safety tests, the present study sought to determine potential developmental toxicity (in female rats) and genotoxicity (in male mice) of KACY. Pregnant female rats were divided into six groups: the negative control (vehicle), the positive control (250 mg/kg of acetylsalicylic acid (ASA)), and four experimental groups (50, 250, 500 and 1000 mg/kg of KACY). To evaluate genotoxicity by in vivo micronuclei (MN) and sister chromatid exchange (SCE) tests, male mice were divided into five groups: the negative control (vehicle), the positive control (1.5 and 2.5 mg/kg of doxorubicin for MN and SCE, respectively), and three experimental groups (50, 500 and 1000 mg/kg of KACY). All treatments were administered by oral gavage. A slight maternal toxicity was evidenced by lower weight gain for rats receiving 500 and 1000 mg/kg of KACY, but no fetal malformations were found. However, there were less live fetuses/litter and greater post-implantation loss/litter at these two doses. Manifestations of developmental toxicity were limited to a higher rate of skeletal alterations. The MN tests did not evidence genotoxicity or cytotoxicity. KACY caused a slightly but significantly increased frequency of SCE. Although KACY-treated rats had skeletal alterations, these apparently were not caused by a mechanism of genotoxicity. Furthermore, the same administration in adult male mice did not produce genotoxicity. Hence, KACY herein proved to be safe for rats during the period of organogenesis.

Liquid self-diffusion of H2O and DMF molecules in Co-MOF-74: molecular dynamics simulations and dielectric spectroscopy studies.

In this work we use molecular dynamics simulations to study the diffusion of N,N-dimethylformamide (DMF) and H2O as a function of temperature within the well-known metal-organic framework Co2(dobdc)·[G] (G = 2DMF·1H2O), also known as Co-MOF-74. The molecular dynamics simulations show that the diffusivity of guest molecules, which is almost negligible at low temperatures (T < 200 K), increases in the range of 200 < T (K) < 400 up to 3 and 4 orders of magnitude for DMF and H2O, respectively. This molecular diffusion can be easily detected by dielectric spectroscopy as it gives rise to extrinsic interfacial polarization effects that result in an apparent "colossal" dielectric constant at room temperature, εr' ∼ 42 000 (T = 300 K, ν = 10 Hz). Furthermore, the measured dielectric constant exhibits a thermal dependence similar to that of the diffusion coefficient, revealing the parallelism of the dielectric response and the molecular diffusion as a function of temperature. These results highlight: (a) the great utility of the fast and non-destructive dielectric and impedance spectroscopy techniques for the study and detection of the molecular transport of small polar molecules within porous metal-organic frameworks and related materials; (b) the peculiarity and uniqueness of MOF materials with "medium" size nanopores containing guest molecules as they are solid materials in which the guest molecules display a liquid state-like behaviour close to room temperature; and

A contrast set mining based approach for cancer subtype analysis.

The task of detecting common and unique characteristics among different cancer subtypes is an important focus of research that aims to improve personalized therapies. Unlike current approaches mainly based on predictive techniques, our study aims to improve the knowledge about the molecular mechanisms that descriptively led to cancer, thus not requiring previous knowledge to be validated. Here, we propose an approach based on contrast set mining to capture high-order relationships in cancer transcriptomic data. In this way, we were able to extract valuable insights from several cancer subtypes in the form of highly specific genetic relationships related to functional pathways affected by the disease. To this end, we have divided several cancer gene expression databases by the subtype associated with each sample to detect which gene groups are related to each cancer subtype. To demonstrate the potential and usefulness of the proposed approach we have extensively analysed RNA-Seq gene expression data from breast, kidney, and colon cancer subtypes. The possible role of the obtained genetic relationships was further evaluated through extensive literature research, while its prognosis was assessed via survival analysis, finding gene expression patterns related to survival in various cancer subtypes. Some gene associations were described in the literature as potential cancer biomarkers while other results have been not described yet and could be a starting point for future research.

Anatomical categorization of isolated non-focal dystonia: novel and existing patterns using a data-driven approach.

According to expert consensus, dystonia can be classified as focal, segmental, multifocal, and generalized, based on the affected body distribution. To provide an empirical and data-driven approach to categorizing these distributions, we used a data-driven clustering approach to compare frequency and co-occurrence rates of non-focal dystonia in pre-defined body regions using the Dystonia Coalition (DC) dataset. We analyzed 1,618 participants with isolated non-focal dystonia from the DC database. The analytic approach included construction of frequency tables, variable-wise analysis using hierarchical clustering and independent component analysis (ICA), and case-wise consensus hierarchical clustering to describe associations and clusters for dystonia affecting any combination of eighteen pre-defined body regions. Variable-wise hierarchical clustering demonstrated closest relationships between bilateral upper legs (distance = 0.40), upper and lower face (distance = 0.45), bilateral hands (distance = 0.53), and bilateral feet (distance = 0.53). ICA demonstrated clear grouping for the a) bilateral hands, b) neck, and c) upper and lower face. Case-wise consensus hierarchical clustering at k = 9 identified 3 major clusters. Major clusters consisted primarily of a) cervical dystonia with nearby regions, b) bilateral hand dystonia, and c) cranial dystonia. Our data-driven approach in a large dataset of isolated non-focal dystonia reinforces common segmental patterns in cranial and cervical regions. We observed unexpectedly strong associations between bilateral upper or lower limbs, which suggests that symmetric multifocal patterns may represent a previously underrecognized dystonia subtype.

Aggregation behavior of western spotted cucumber beetle (Coleoptera: Chrysomelidae) in vegetable cropping systems.

Aggregation behavior of adult western spotted cucumber beetles (Diabrotica undecimpunctata undecimpunctata Mannerheim) (Coleoptera: Chrysomelidae) was examined in six snap bean (Phaseolus vulgaris) fields adjacent to corn fields in western Oregon in 2004-2006. In the 2004 and 2005 studies, sweep net sampling was used to estimate beetle numbers along transect lines running perpendicular to the edges of the bean fields next to sweet corn fields. Beetles were collected from the fields and dissected to determine sex and egg development. Beetles were highly aggregated along the edge of the snap bean field next to the sweet corn, with the highest number of beetles occurring within the first meter next to the edge. Beetles in the aggregation areas were mostly females (average female to male ratio of 8.4 to 1), whereas beetles in the field section away from the edges were mostly male (female to male ratio of 0.6 to 1). Of the females collected in the aggregation areas, an average of 53% contained developing or fully developed eggs. In the 2006 study, beetle densities in the field edges were compared with densities within the fields in 40 bean fields with adjacent corn fields. Linear regression analysis showed that, across fields, nearly two times as many beetles were found in the field borders as in the rest of the field. These data suggest modifying traditional field scouting protocol to include field margins when a bean field is adjacent to or near a sweet corn field. A pest management strategy of only spraying the edges of bean fields containing beetle aggregations shows potential for significant pesticide reduction, as well as reducing risk of economic loss from crops harvested from the highly aggregated areas.

Acetylene Storage and Separation Using Metal-Organic Frameworks with Open Metal Sites.

Efficient separation and storage of gas streams involving light hydrocarbons is essential for industrial applications. These hydrocarbons are widely used as energy resources and/or chemical raw materials in various chemical reactions. Here, we focus on the separation of acetylene from methane and carbon dioxide. The separation of acetylene from carbon dioxide is, in particular, challenging due to the similar kinetic diameters and boiling points of the molecules. In recent years, considerable progress has been made in adsorption-based separations using porous metal-organic frameworks (MOFs). Most reported studies are experimental. We present a computational study on these gas separations using a variety of MOFs. This allows investigation of the competitive gas adsorption, which is experimentally challenging, as well as understanding the adsorption mechanisms at the molecular level, which in turn allows further experimental MOF design for this application. MOFs with open metal sites, and particularly Fe-MOF-74, seem to be good for this separation, with a trade-off between physical adsorption capacity and selectivity. Based on experimental single-adsorption isotherms at various temperatures, we developed and validated a specific parameterization to account for the interactions of the olefin with the open metal sites. In addition to volumetric and calorimetric adsorption, we comprehensively investigate the characteristics of the interaction between the MOFs and the guest molecules in terms of binding sites and density profiles. The overall agreement of our simulated results with experimental data for pure components points to the reliability of the models and methods to successfully predict the separation of mixtures.

Improving Olefin Purification Using Metal Organic Frameworks with Open Metal Sites.

The separation and purification of light hydrocarbons is challenging in the industry. Recently, a ZJNU-30 metal-organic framework (MOF) has been found to have the potential for adsorption-based separation of olefins and diolefins with four carbon atoms [H. M. Liu et al. Chem.-Eur. J. 2016, 22, 14988-14997]. Our study corroborates this finding but reveals Fe-MOF-74 as a more efficient candidate for the separation because of the open metal sites. We performed adsorption-based separation, transient breakthrough curves, and density functional theory calculations. This combination of techniques provides an extensive understanding of the studied system. Using this MOF, we propose a separation scheme to obtain a high-purity product.

Micelle Formation in Aqueous Solutions of Room Temperature Ionic Liquids: A Molecular Dynamics Study.

1-Alkyl-3-methylimidazolium cations in the presence of water are used as a test system to study by molecular dynamics the formation of micelles in aqueous mixtures of highly anisotropic room temperature ionic liquids (IL). Structural properties, i.e., radial distribution functions (RDF) and transport parameters, such as diffusion coefficients and conductivities, are computed as a function of the IL/water mole fraction. The concentration plots reveal a sharp change of the slope of both the cation self-diffusion coefficient and the first peak of the head-head RDF at approximately the same value of the concentration. This transition, considered as a measure of a critical micellar concentration, appears only for the most anisotropic systems, composed of longer alkyl chains. The formation of the micelles is confirmed from the analysis of the tail-tail and cation-water RDFs. As a general result, we found that the larger the anisotropy of the ionic liquid the lower the critical concentration and the larger the proportion of monomers forming part of the micelles. The molecular dynamics predictions are in line with the experimental evidence reported for these systems.

[Carcinoma of the penis. Our experience and review of the literature]. / Carcinoma de pene. Nuestra experiencia y revisión de la literatura.

Penile carcinoma is a rather infrequent neoplasia with an approximate annual rate of 1 to 2 cases per 100,000 inhabitants. In Spain, its presentation is rare, corresponding to 10.42% of all tumors and 0.7% of all malignant tumors of the male. In this report, the casuistic of our Department between the years 1978 and 1987 is presented. Ten patients diagnosed of penile carcinoma were treated, representing 0.1% of all the urological tumors seen during that period. Special emphasis has been placed on the need to perform national multicenter studies, due to the rare finding of such pathology. From an etiopathogenic perspective, chronic inflammation due to smegma accumulation and the presence of a prepuce seem necessary for the development of this pathology. The role of oncogenic viruses still remains to be cleared. After treatment, which was mainly surgical, a global survival rate of 60% was obtained with a follow-up period ranging from 1 month to 7 years. After pointing out several anatomical considerations relating to the lymph drainage of the penis, the different therapeutic alternatives (surgery, radiotherapy, chemotherapy) in the treatment of penile carcinoma were discussed.

[Renal outcome in myelodysplastic patients with untreated, risky vesico-sphincter dysfunction]. / Destino renal en los pacientes mielodisplásicos con disfunciones vesico-esfinterianas de riesgo no tratadas.

Poor vesical accommodation with competent sphincter system and bladder-sphincter dyssynergy are major risk factors for renal function in patients with myelomeningocele. We present four cases with these urodynamic features and we analyse renal variation with time in relation to these, pointing out the poor evolution. We emphasize the need for urodynamic study with simultaneous radiology and early treatment when these risk factors exist.

[Upper urinary tract fistulas in renal transplantation]. / Fístulas del tramo urinario superior en el trasplante renal.

237 kidney transplants were performed in our department in a period running from November 1979 to October 1986. Out of this total number of transplants we analyzed the incidence of fistulas of the upper urinary tract, which in our series is 3.3%. Following a study protocol of these patients referring to multiple parameters, we conclude that in our series fistulas of the upper urinary tract appear precociously (less than 45 days post-transplant) and in connection with acute rejection episodes (high doses of steroids). On the basis of anatomopathological criteria we establish that its treatment has to be surgical and a meticulous surgical extraction technique is essential for its prevention.

[Infiltrating transitional carcinoma of the bladder (4). Our approach to stage pT2 and critique of other risk factors. Multifactorial analysis]. / Carcinoma transicional infiltrante de vejiga. (4a parte). Nuestra actitud frente al estadio pT2 y crítica de otros factores de riesgo. Análisis multifactorial.

From the analysis of our experience with pT2 and pT3a tumours it could be deduced that the former have better prognosis. The papillary appearance, invasion in a wide front and extent, whether with good or moderate differentiation, in T2 are signs of good prognosis, as well as the non-existence of unilateral dilation or an effaced kidney. Considering the good evolution obtained with radical cystectomy only, these patients should be recruited for study in order to see whether evolution with bladder preservation is similar. Patients with pT2 tumours should not be included in protocols to evaluate the efficacy of adjuvant therapies used with surgery. The evolution is not equivalent to that expected in tumours of deeper invasion.

[Surgical complications in 479 renal transplantations]. / Complicaciones quirúrgicas en 479 trasplantes renales.

Exposition of results obtained from the review of the surgical complications found in a series of 479 renal transplantations performed between 1978 and 1992 in our centre, although some of them lack clinical relevance. There was fluid accumulation in 69 patients, distributed between 31 perirenal haematoma. 17 lymphocele, 13 urinoma, 5 perirenal abscesses and 3 mixed. 27.7% required no action. Frequency of renal rupture was 18 cases, 9 due to acute rejection and 9 to vascular thrombosis. Incidence of urinary obstruction was 4.8% with 5.8% of urinary fistula. With regard to the surgical wound, 9 infections, 7 haematomas, 1 eventration and 1 necrotizing fasciitis were observed. Vascular complications consisted in 10 arterial thrombosis, 10 venous thrombosis, 5 mixed thrombosis and 31 arterial stenosis. Treatment instituted for the various cases, its evolution, and an statistical study of risk factors are illustrated.

[Diagnostic yield of Echo-Doppler in dysfunction of the grafted kidney]. / Rentabilidad diagnóstica del eco-Doppler en la disfunción del injerto renal.

The study's goal is to analyze the usefulness of Eco-Doppler in the knowledge of renal graft hemodynamics and the description of its dysfunction. 234 examinations were performed in 110 patients. Acceleration, mean rate (MR), maximum systolic rate (MXSR) and minimal diastolic rate (MNDR), as well as resistance index (RI) and pulsatility index (PI) were determined in the external iliac, renal, segmentary, interlobular and arcuate arteries. RI and PI, as well as MXSR and the acceleration are higher in the extra-parenchymatous versus the intra-parenchymatous beds. Peak MR and MNDR values are reached in the renal artery. Termino-lateral to external iliac arterial anastomosis conditions higher MXSRs in the renal artery as opposed to termino-terminal to hypogastric artery (p < 0.05). In the arcuate artery, RI > 0.8 is reached in 51.6% of acute tubular necrosis (ATN), 46.9% of acute rejections (CR), 46.3% of chronic rejection (AR), 21% of grafts with cyclosporin-induced nephrotoxicity (NFX) and 12.5% of normal functioning kidneys isolated chance analysis with Eco-Doppler does not distinguish between AR and ATN. A dysfunctional graft with an RR in the arcuate artery of nearly 9.7 suggests NFX, but AR with interstitial predominance cannot be ruled out.

[Instability of the detrusor. Treatment with oxybutynin chloride (Ditropan) in children]. / Inestabilidad del detrusor. Tratamiento con cloruro de oxibutinina (Ditropan) en niños.

We study the effect of oxybutynin chloride (Ditropan) in a random sample of 24 children with ages ranging from 5 to 14 years, diagnosed as having vesical instability from both the clinical and urodynamic standpoints. These effects were evaluated after a period of treatment that ranged from 10 to 36 months (x = 20). We obtained overall clinical improvement in 87.5%, and improvement of urodynamic alterations in 83.3% of the patients. We single out the beneficial effect of oxybutynin chloride with prolonged treatments, in instability of the detrusor, as well as its good tolerance.

[Rupture of the graft in kidney transplant. Our caseload]. / Rotura del injerto en el trasplante renal. Nuestra casuística.

316 kidney transplants were carried out in the Ramón y Cajal Hospital between November 1979 and December 1988. The number of breakages was 7. In this paper we analyse the incidence of this complication as well as the etiopathogeny of the process, highlighting the relationship between the appearance of acute rejection, alterations in coagulation, and instrumental manoeuvres carried out on the graft, especially in the first days after transplant. The clinical pattern usually displayed was pain with swelling and pasting in the area of the implant, along with hypotension, oliguria and deterioration of kidney function. We underline the importance of echography as the follow-up method in the early detection of hematomas, perirenal collections, etc., which, together with the preceding clinical data, will orientate us towards an early diagnosis. We study the possible relationship of this complication with different factors, singling out the reduced frequency of appearance after the advent of cyclosporin and its use as an immunosuppressive drug. We advocate the conservation of the implant with three dimensional corsseting, provided this is feasible and the general conditions of the patient so permit.

[Rupture of simple renal cyst after minimal renal injury]. / Rotura de quiste renal simple tras traumatismo renal mínimo.

A case is presented of minimum renal trauma, leading to a retroperitoneal hematoma as a consequence of a simple renal cyst rupture as well as an artery contained therein. The etiopathogenicity of this phenomenon is commented. The different clinical manifestations of renal trauma are highlighted, as well as the suspicion of previous renal pathology when a large renal lesion is found secondary to minimum renal trauma. The approach of the renal pediculum must be the first step in the surgical treatment of renal trauma.

[Treatment of recurrent bladder surface tumors with laser Nd:Yag: a single-year experience]. / Tratamiento de los tumores vesicales superficiales recidivantes con laser Nd:Yag: un año de experiencia.

Management of surface vesical tumours using laser photocoagulation has proven to be a safe and effective method. The technique can be performed under anaesthetic sedation and in the outpatient clinic environment thus allowing a considerable cost saving and the reduction of hospital's waiting lists. Throughout 1990, 47 patients with relapsing vesical tumours were treated in 55 sessions. Most cases were performed on ambulatory patients with a low complications rate and an estimated saving of 18,326,400 pesetas as compared to transurethral resection.

[Primary testicular lymphoma. Report of a new case and review of the literature]. / Linfoma testicular primario. Aportación de un nuevo caso y revisión de la literatura.

Primary testicular lymphoma is an uncommon testicular tumour that accounts for no more than 9% of all testicular tumours in those series with higher incidence; testicular lymphoma as haematopoietic tumours are also rare accounting for just 1% of all lymphomas; but due to their highly malignant histopathology they may become highly aggressive tumours. Patient age at presentation is over 60 years old which makes it the most frequent tumour for this age group. There is no standard protocol to treat this malignancy due to lack of extensive series. We contribute one case and make a literature review discussing the current therapeutic trends for this disease.