Synthesis and Evaluation of Small Molecule Inhibitors of the Androgen Receptor N-Terminal Domain.

The androgen receptor (AR) is central to prostate cancer pathogenesis and has been extensively validated as a drug target. However, small-molecule anti-androgen therapies remain limited due to resistance and will eventually fail to suppress tumor growth, resulting in progression to castration-resistant prostate cancer (CRPC). The intrinsically disordered N-terminal domain (NTD) is crucial for AR transactivation and has been investigated as a suitable target in the presence of ligand binding domain mutations. A screening campaign identified biaryl isoxazole compound 7 as a weak inhibitor of the AR NTD. A library of biaryl analogues were synthesized, and their biological activities were assessed in a VCaP cell-based luciferase reporter gene assay. A structure-activity relationship (SAR) study revealed that indazole analogue 16 exhibited increased potency and favorable physicochemical properties with a benchmarked pharmacokinetic profile, providing a suitable starting point for further optimization of 16 as a CRPC therapeutic in the presence of AR mutations.

Current and emerging approaches to noncompetitive AR inhibition.

The androgen receptor (AR) has been shown to be a key determinant in the pathogenesis of castration-resistant prostate cancer (CRPC). The current standard of care therapies targets the ligand-binding domain of the receptor and can afford improvements to life expectancy often only in the order of months before resistance occurs. Emerging preclinical and clinical compounds that inhibit receptor activity via differentiated mechanisms of action which are orthogonal to current antiandrogens show promise for overcoming treatment resistance. In this review, we present an authoritative summary of molecules that noncompetitively target the AR. Emerging small molecule strategies for targeting alternative domains of the AR represent a promising area of research that shows significant potential for future therapies. The overall quality of lead candidates in the area of noncompetitive AR inhibition is discussed, and it identifies the key chemotypes and associated properties which are likely to be, or are currently, positioned to be first in human applications.

Functionalized Tetrazoles as Latent Active Esters in the Synthesis of Amide Bonds.

We report the use of N-2,4-dinitrophenyltetrazoles as latent active esters (LAEs) in the synthesis of amide bonds. Activating the tetrazole generates an HOBt-type active ester without the requirement for exogenous coupling agents. The methodology was widely applicable to a range of substrates, with up to quantitative yields obtained. The versatility and functional group tolerance were exemplified with the one-step synthesis of various pharmaceutical agents and the N-acylation of resin-bound peptides.

Resultados a mediano plazo de la prótesis invertida en la artropatía de manguito / Results in the medium long term of the reverse shoulder prosthesis in the cuff arthropathy

Resumen: Introducción: El estadio final de la artropatía de manguito (AM) genera dolor e invalidez, el tratamiento mediante artroplastía invertida (AI) muestra buenos índices de reducción de dolor y mejoras en movilidad. El objetivo de nuestro trabajo fue evaluar de manera retrospectiva los resultados a mediano plazo de la artroplastía invertida de hombro en nuestro centro. Material y método: Retrospectivamente analizamos 21 pacientes (23 prótesis) sometidos a AI con el diagnóstico de AM. La edad media fue de 75.21 años. El seguimiento mínimo fue de 60 meses. Analizamos las escalas ASES, DASH y CONSTANT preoperatorias y en la última visita de seguimiento. Se analizó la escala VAS preoperatoria y postoperatoria y rango de movilidad preoperatoria y postoperatoria. Resultados: Mejoraron todas las escalas funcionales y dolor (p < 0.001). ASES en 38.91 puntos (IC 95% 30.97-46.84); CONSTANT en 40.89 puntos (IC 95% 34.57-47.21); DASH en 52.65 puntos (IC 95% 46.31-59.0) p < 0.001; y 5.41 puntos (IC 95% 4.31-6.50) en VAS. Mejoraron con significación estadística la flexión (66.52o a 113.91o); y la abducción (63.69o a 105.85o). No obtuvimos significación estadística en rotación externa ni en rotación interna. Aparecieron complicaciones en 14 pacientes; 11 notching glenoideo, una infección crónica, una infección tardía y una fractura intraoperatoria de glenoides. Conclusiones: La AI de hombro representa una alternativa eficaz para el tratamiento de la AM. Puede esperarse alivio del dolor y una mejoría en la flexión y abducción del hombro; la ganancia en rotaciones es poco predecible.

Abstract: Introduction: The final stage of rotator cuff tear arthropathy generates pain and disability, treatment with reverse shoulder arthroplasty shows in different published studies good rates of pain reduction and improvements in mobility. the objective of our study was to retrospectively evaluate the medium-term results of inverted shoulder replacement at our center. Material and methods: Retrospectively, we analyzed 21 patients (23 prosthetics) undergoing reverse shoulder arthroplasty with the diagnosis of rotator cuff tear arthropathy. The average age of patients was 75.21 years The minimum follow-up was 60 months. We analyzed in all preoperative ASES, DASH and CONSTANT patients, and a new functional assessment was made using these same scales at the last follow-up visit. We analyzed pre and postoperative VAS as well as pre and postoperative mobility range. Results: We achieved a statistically significant improvement in all functional scale and pain values (p < 0.001). The ASES scale showed an improvement of 38.91 points (95% CI 30.97-46.84); the 40.89-point CONSTANT scale (95% 34.57-47.21) and the 52.65-point DASH scale (95% 46.31-59.0) p < 0.001. We found an improvement of 5.41 points (95% CI 4.31-6.50) on the VAS scale. We also achieved a statistically significant improvement in flexion values 66.52o to 113.91o degrees; abduction 63.69o to 105.85o degrees at the end of the follow-up. We did not get statistical significance in terms of external rotation but with a tendency to improve in the obtained values; instead in internal rotation we obtained results that showed a tendency to worsen. Complications occurred during follow-up in 14 patients; 11 in relation to notching glenoid, one patient with a chronic infection, one patient with a late infection and one intraoperative fracture of glenoid. Conclusions: Reverse shoulder arthroplasty is an effective treatment of rotator cuff arthropathy. Pain relief and improvement in shoulder flexion and abduction can be expected especially; the gain in rotations is unpredictable.

Simplified risk-prediction for benchmarking and quality improvement in emergency general surgery. Prospective, multicenter, observational cohort study.

BACKGROUND AND AIMS: Emergency General Surgery (EGS) conditions account for millions of deaths worldwide, yet it is practiced without benchmarking-based quality improvement programs. The aim of this observational, prospective, multicenter, nationwide study was to determine the best benchmark cutoff points in EGS, as a reference to guide improvement measures. METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending EGS patients on a 24-h, 7-days a week basis, enrolled consecutive patients requiring an emergent/urgent surgical procedure. Patients were stratified into cohorts of low (i.e., expected morbidity risk <33%), middle and high risk using the novel m-LUCENTUM calculator. RESULTS: A total of 7258 patients were included; age (mean ± SD) was 51.1 ± 21.5 years, 43.2% were female. Benchmark cutoffs in the low-risk cohort (5639 patients, 77.7% of total) were: use of laparoscopy ≥40.9%, length of hospital stays ≤3 days, any complication within 30 days ≤ 17.7%, and 30-day mortality ≤1.1%. The variables with the greatest impact were septicemia on length of hospital stay (21 days; adjusted beta coefficient 16.8; 95% CI: 15.3 to 18.3; P < .001), and respiratory failure on mortality (risk-adjusted population attributable fraction 44.6%, 95% CI 29.6 to 59.6, P < .001). Use of laparoscopy (odds ratio 0.764, 95% CI 0.678 to 0.861; P < .001), and intraoperative blood loss (101-500 mL: odds ratio 2.699, 95% CI 2.152 to 3.380; P < .001; and 500-1000 mL: odds ratio 2.875, 95% CI 1.403 to 5.858; P = .013) were associated with increased morbidity. CONCLUSIONS: This study offers, for the first time, clinically-based benchmark values in EGS and identifies measures for improvement.

Amide Bond Formation via the Rearrangement of Nitrile Imines Derived from N-2-Nitrophenyl Hydrazonyl Bromides.

We report how the rearrangement of highly reactive nitrile imines derived from N-2-nitrophenyl hydrazonyl bromides can be harnessed for the facile construction of amide bonds. This amidation reaction was found to be widely applicable to the synthesis of primary, secondary, and tertiary amides and was used as the key step in the synthesis of the lipid-lowering agent bezafibrate. The orthogonality and functional group tolerance of this approach was exemplified by the N-acylation of unprotected amino acids.

[Results in the medium long term of the reverse shoulder prosthesis in the cuff arthropathy]. / Resultados a mediano plazo de la prótesis invertida en la artropatía de manguito.

INTRODUCTION: the final stage of rotator cuff tear arthropathy generates pain and disability, treatment with reverse shoulder arthroplasty shows in different published studies good rates of pain reduction and improvements in mobility. the objective of our study was to retrospectively evaluate the medium-term results of inverted shoulder replacement at our center. MATERIAL AND METHODS: retrospectively, we analyzed 21 patients (23 prosthetics) undergoing reverse shoulder arthroplasty with the diagnosis of rotator cuff tear arthropathy. The average age of patients was 75.21 years The minimum follow-up was 60 months. We analyzed in all preoperative ASES, DASH and CONSTANT patients, and a new functional assessment was made using these same scales at the last follow-up visit. We analyzed pre and postoperative VAS as well as pre and postoperative mobility range. RESULTS: we achieved a statistically significant improvement in all functional scale and pain values (p < 0.001). The ASES scale showed an improvement of 38.91 points (95% CI 30.97-46.84); the 40.89-point CONSTANT scale (95% 34.57-47.21) and the 52.65-point DASH scale (95% 46.31-59.0) p < 0.001. We found an improvement of 5.41 points (95% CI 4.31-6.50) on the VAS scale. We also achieved a statistically significant improvement in flexion values 66.52o to 113.91o degrees; abduction 63.69o to 105.85o degrees at the end of the follow-up. We did not get statistical significance in terms of external rotation but with a tendency to improve in the obtained values; instead in internal rotation we obtained results that showed a tendency to worsen. Complications occurred during follow-up in 14 patients; 11 in relation to notching glenoid, one patient with a chronic infection, one patient with a late infection and one intraoperative fracture of glenoid. CONCLUSIONS: reverse shoulder arthroplasty is an effective treatment of rotator cuff arthropathy. Pain relief and improvement in shoulder flexion and abduction can be expected especially; the gain in rotations is unpredictable.

INTRODUCCIÓN: el estadio final de la artropatía de manguito (AM) genera dolor e invalidez, el tratamiento mediante artroplastía invertida (AI) muestra buenos índices de reducción de dolor y mejoras en movilidad. El objetivo de nuestro trabajo fue evaluar de manera retrospectiva los resultados a mediano plazo de la artroplastía invertida de hombro en nuestro centro. MATERIAL Y MÉTODO: retrospectivamente analizamos 21 pacientes (23 prótesis) sometidos a AI con el diagnóstico de AM. La edad media fue de 75.21 años. El seguimiento mínimo fue de 60 meses. Analizamos las escalas ASES, DASH y CONSTANT preoperatorias y en la última visita de seguimiento. Se analizó la escala VAS preoperatoria y postoperatoria y rango de movilidad preoperatoria y postoperatoria. RESULTADOS: mejoraron todas las escalas funcionales y dolor (p < 0.001). ASES en 38.91 puntos (IC 95% 30.97-46.84); CONSTANT en 40.89 puntos (IC 95% 34.57-47.21); DASH en 52.65 puntos (IC 95% 46.31-59.0) p < 0.001; y 5.41 puntos (IC 95% 4.31-6.50) en VAS. Mejoraron con significación estadística la flexión (66.52o a 113.91o); y la abducción (63.69o a 105.85o). No obtuvimos significación estadística en rotación externa ni en rotación interna. Aparecieron complicaciones en 14 pacientes; 11 notching glenoideo, una infección crónica, una infección tardía y una fractura intraoperatoria de glenoides. CONCLUSIONES: la AI de hombro representa una alternativa eficaz para el tratamiento de la AM. Puede esperarse alivio del dolor y una mejoría en la flexión y abducción del hombro; la ganancia en rotaciones es poco predecible.

No changes in adolescent's sedentary behaviour across Europe between 2002 and 2017.

BACKGROUND: Public health organizations have been alerted to the high levels of sedentary behaviour (SB) among adolescents as well as to the health and social consequences of excess sedentary time. However, SB changes of the European Union (EU) adolescents over time have not been reported yet. This study aimed to identify SB of the EU adolescents (15-17 years) in four-time points (2002, 2005, 2013 and 2017) and to analyse the prevalence of SB according to the sex. METHODS: SB of 2542 adolescents (1335 boys and 1207 girls) as a whole sample and country-by-country was analysed in 2002, 2005, 2013, and 2017 using the Sport and Physical Activity EU Special Eurobarometers' data. SB was measured using the sitting time question from the short version of the International Physical Activity Questionnaire (IPAQ), such that 4h30min of daily sitting time was the delineating point to determine excess SB behaviour (≥4h30min of sitting time) or not (≤4h30min of sitting time). A χ2 test was used to compare the prevalence of SB between survey years. Furthermore, SB prevalence between sexes was analysed using a Z-Score test for two population proportions. RESULTS: The prevalence of SB among EU adolescents across each of the four survey years ranged from 74.2 and 76.8%, rates that are considered high. High levels of SB were also displayed by both sexes (girls: 76.8 to 81.2%; boys: 71.7 to 76.7%). No significant differences in the prevalence of SB among years (p > 0.05) were found for the whole sample, and for either girls or boys. Also, no significant differences in the prevalence of SB between girls and boys were found. CONCLUSION: The SB prevalence in European adolescents is extremely high (76.8% in 2017) with no differences between girls and boys. No significant improvements have been seen between 2002 and 2017. Eurobarometer should increase the adolescents' sample to make possible benchmarking comparisons among the EU countries and extend the survey to the younger children population.

Yebes 40 m radio telescope and the broad band NANOCOSMOS receivers at 7 mm and 3 mm for line surveys.

CONTEXT: Yebes 40m radio telescope is the main and largest observing instrument at Yebes Observatory and it is devoted to Very Long Baseline Interferometry (VLBI) and single dish observations since 2010. It has been covering frequency bands between 2 GHz and 90 GHz in discontinuous and narrow windows in most of the cases, to match the current needs of the European VLBI Network (EVN) and the Global Millimeter VLBI Array (GMVA). AIMS: Nanocosmos project, a European Union funded synergy grant, opened the possibility to increase the instantaneous frequency coverage to observe many molecular transitions with single tunnings in single dish mode. This reduces the observing time and maximises the output from the telescope. METHODS: We present the technical specifications of the recently installed 31.5 - 50GHz (Q band) and 72 - 90.5 GHz (W band) receivers along with the main characteristics of the telescope at these frequency ranges. We have observed IRC+10216, CRL 2688 and CRL 618, which harbour a rich molecular chemistry, to demonstrate the capabilities of the new instrumentation for spectral observations in single dish mode. RESULTS: The results show the high sensitivity of the telescope in the Q band. The spectrum of IRC+10126 offers a signal to noise ratio never seen before for this source in this band. On the other hand, the spectrum normalised by the continuum flux towards CRL 618 in the W band demonstrates that the 40 m radio telescope produces comparable results to those from the IRAM 30 m radio telescope, although with a smaller sensitivity. The new receivers fulfil one of the main goals of Nanocosmos and open the possibility to study the spectrum of different astrophysical media with unprecedented sensitivity.

[Results of the treatment of primary glenohumeral osteoarthritis through hemiarthroplasty]. / Resultados del tratamiento de la artrosis glenohumeral primaria mediante hemiartroplastía.

INTRODUCTION: Glenohumeral osteoarthritis leads to a functional loss and a decrease in the quality of life of many patients that suffers it. Currently there is no agreement on the use of hemiarthroplasty or total arthroplasty as definitive treatment. The objective is to show the results of the treatment of primary glenohumeral osteoarthritis through hemiarthroplasty in our service. MATERIAL AND METHODS: We reviewed 14 patients (19 hemiarthroplasties) performed between 2004 and 2013 in patients diagnosed with primary glenohumeral osteoarthritis without glenoid morphological anomaly. We managed to collect data from eight patients (11 hemiarthroplasties), assessing functional status, pain, and performing activities of daily living using the Constant, ASES and DASH scores preoperatively and at five years of minimum follow-up (range 5-11 years), as well as related complications. The preoperative status was compared to the end of the follow-up. RESULTS: A significant improvement was found in all the parameters analyzed in the study (p. CONCLUSION: < 0.05). The average pain in EVA score decreased from 8.89 to 2.67. The ASES improved from 13.51 to 63. 51 half point. The Constant increase of 20.11 points to 65.11 points. The mean preoperative score in the DASH score was 73.68 and 28.30 postoperatively. The average survival of the implant was 81.82% in the seven years of average follow-up. Shoulder hemiarthroplasty obtains good functional results in the treatment of primary glenohumeral osteoarthritis with few complications. The cause of the failure were glenoid erosion in all the cases.

INTRODUCCIÓN: La artrosis glenohumeral conlleva a una pérdida funcional y a una disminución de la calidad de vida de muchos pacientes. Actualmente, no existe consenso en cuanto al uso de la hemiartroplastía o la artroplastía total como tratamiento definitivo para este padecimiento. El objetivo es mostrar los resultados del tratamiento de la artrosis glenohumeral primaria mediante hemiartroplastía en nuestro servicio. MATERIAL Y MÉTODOS: Revisamos 19 hemiartroplastías (14 pacientes) realizadas entre 2004 y 2013 en pacientes con artrosis glenohumeral primaria sin alteración morfológica glenoidea. Se recabaron los datos de ocho pacientes (11 hemiartroplastías), valorándose el estado funcional, el dolor y la realización de actividades de la vida diaria mediante las escalas Constant, ASES y DASH preoperatorias, a los cinco años de seguimiento mínimo (rango 5-11 años), así como las complicaciones presentadas. Se comparó el estado preoperatorio y al final del seguimiento. RESULTADOS: Se encontró una mejoría estadísticamente significativa (p. CONCLUSIÓN: < 0.05) en todos los parámetros analizados en el estudio. La media del dolor en la escala EVA disminuyó de 8.89 a 2.67. La escala ASES mejoró de 13.51 a 63.51 puntos de media. El Constant aumentó de 20.11 a 65.11 puntos. La puntuación media preoperatoria en la escala DASH fue de 73.68 y la postoperatoria de 28.30 puntos. La supervivencia media del implante fue de 81.82% a los siete años de seguimiento medio. Obtuvimos buenos resultados funcionales con la artrosis glenohumeral primaria, presentándose pocas complicaciones. La causa del fracaso fue la erosión glenoidea.

Resultados del tratamiento de la artrosis glenohumeral primaria mediante hemiartroplastía / Results of the treatment of primary glenohumeral osteoarthritis through hemiarthroplasty

Resumen: Introducción: La artrosis glenohumeral conlleva a una pérdida funcional y a una disminución de la calidad de vida de muchos pacientes. Actualmente, no existe consenso en cuanto al uso de la hemiartroplastía o la artroplastía total como tratamiento definitivo para este padecimiento. El objetivo es mostrar los resultados del tratamiento de la artrosis glenohumeral primaria mediante hemiartroplastía en nuestro servicio. Material y métodos: Revisamos 19 hemiartroplastías (14 pacientes) realizadas entre 2004 y 2013 en pacientes con artrosis glenohumeral primaria sin alteración morfológica glenoidea. Se recabaron los datos de ocho pacientes (11 hemiartroplastías), valorándose el estado funcional, el dolor y la realización de actividades de la vida diaria mediante las escalas Constant, ASES y DASH preoperatorias, a los cinco años de seguimiento mínimo (rango 5-11 años), así como las complicaciones presentadas. Se comparó el estado preoperatorio y al final del seguimiento. Resultados: Se encontró una mejoría estadísticamente significativa (p < 0.05) en todos los parámetros analizados en el estudio. La media del dolor en la escala EVA disminuyó de 8.89 a 2.67. La escala ASES mejoró de 13.51 a 63.51 puntos de media. El Constant aumentó de 20.11 a 65.11 puntos. La puntuación media preoperatoria en la escala DASH fue de 73.68 y la postoperatoria de 28.30 puntos. La supervivencia media del implante fue de 81.82% a los siete años de seguimiento medio. Conclusión: Obtuvimos buenos resultados funcionales con la artrosis glenohumeral primaria, presentándose pocas complicaciones. La causa del fracaso fue la erosión glenoidea.

Abstract: Introduction: Glenohumeral osteoarthritis leads to a functional loss and a decrease in the quality of life of many patients that suffers it. Currently there is no agreement on the use of hemiarthroplasty or total arthroplasty as definitive treatment. The objective is to show the results of the treatment of primary glenohumeral osteoarthritis through hemiarthroplasty in our service. Material and methods: We reviewed 14 patients (19 hemiarthroplasties) performed between 2004 and 2013 in patients diagnosed with primary glenohumeral osteoarthritis without glenoid morphological anomaly. We managed to collect data from eight patients (11 hemiarthroplasties), assessing functional status, pain, and performing activities of daily living using the Constant, ASES and DASH scores preoperatively and at five years of minimum follow-up (range 5-11 years), as well as related complications. The preoperative status was compared to the end of the follow-up. Results: A significant improvement was found in all the parameters analyzed in the study (p < 0.05). The average pain in EVA score decreased from 8.89 to 2.67. The ASES improved from 13.51 to 63. 51 half point. The Constant increase of 20.11 points to 65.11 points. The mean preoperative score in the DASH score was 73.68 and 28.30 postoperatively. The average survival of the implant was 81.82% in the seven years of average follow-up. Conclusion: Shoulder hemiarthroplasty obtains good functional results in the treatment of primary glenohumeral osteoarthritis with few complications. The cause of the failure were glenoid erosion in all the cases.

Broad band high resolution rotational spectroscopy for Laboratory Astrophysics.

We present a new experimental setup devoted to the study of gas phase molecules and processes using broad band high spectral resolution rotational spectroscopy. A reactor chamber has been equipped with radio receivers similar to those used by radio astronomers to search for molecular emission in space. The whole Q (31.5-50 GHz) and W bands (72-116.5 GHz) are available for rotational spectroscopy observations. The receivers are equipped with 16×2.5 GHz Fast Fourier Transform spectrometers with a spectral resolution of 38.14 kHz allowing the simultaneous observation of the complete Q band and one third of the W band. The whole W band can be observed in three settings in which the Q band is always observed. Species such as CH3CN, OCS, and SO2 are detected, together with many of their isotopologues and vibrationally excited states, in very short observing times. The system permits automatic overnight observations and integration times as long as 2.4×105 seconds have been reached. The chamber is equipped with a radiofrequency source to produce cold plasmas and with four ultraviolet lamps to study photochemical processes. Plasmas of CH4, N2, CH3CN, NH3, O2, and H2, among other species, have been generated and the molecular products easily identified by their rotational spectrum, and mass spectrometry and optical spectroscopy. Finally, the rotational spectrum of the lowest energy conformer of CH3CH2NHCHO (N-Ethylformamide), a molecule previously characterized in microwave rotational spectroscopy, has been measured up to 116.5 GHz allowing the accurate determination of its rotational and distortion constants and its search in space.

FragLites-Minimal, Halogenated Fragments Displaying Pharmacophore Doublets. An Efficient Approach to Druggability Assessment and Hit Generation.

Identifying ligand binding sites on proteins is a critical step in target-based drug discovery. Current approaches to this require resource-intensive screening of large libraries of lead-like or fragment molecules. Here, we describe an efficient and effective experimental approach to mapping interaction sites using a set of halogenated compounds expressing paired hydrogen-bonding motifs, termed FragLites. The FragLites identify productive drug-like interactions, which are identified sensitively and unambiguously by X-ray crystallography, exploiting the anomalous scattering of the halogen substituent. This mapping of protein interaction surfaces provides an assessment of druggability and can identify efficient start points for the de novo design of hit molecules incorporating the interacting motifs. The approach is illustrated by mapping cyclin-dependent kinase 2, which successfully identifies orthosteric and allosteric sites. The hits were rapidly elaborated to develop efficient lead-like molecules. Hence, the approach provides a new method of identifying ligand sites, assessing tractability and discovering new leads.

Variability in the use of neuroimaging techniques for diagnosis and follow-up of stroke patients. / Grandes variaciones en la utilización de pruebas por imagen en el diagnóstico y seguimiento de los pacientes con ictus.

INTRODUCTION AND OBJECTIVE: Imaging diagnosis is essential for treatment planning in stroke patients. However, use of these techniques varies due to uncertainty about their effectiveness. Our purpose was to describe the use of CT and MRI in stroke and transient ischaemic attack (TIA) over 5years in hospitals belonging to the Canary Islands Health Service and analyse interhospital variability based on routinely collected administrative data. PATIENTS AND METHOD: We gathered the minimum basic dataset (MBDS) from patients diagnosed with stroke or TIA between 2005 and 2010 in 4hospitals. Patients' age, sex, procedures, secondary diagnoses, and duration of hospital stay were also recorded. We conducted a descriptive analysis of patient characteristics and a bivariate analysis using the t test and the chi square test to detect differences between patients assessed and not assessed with MRI. Logistic regression was used to analyse unequal access to MRI. RESULTS AND CONCLUSIONS: Our study included 10,487 patients (8,571 with stroke and 1,916 with TIA). The percentage of stroke patients undergoing a CT scan increased from 89.47% in 2005 to 91.50% in 2010. In these patients, use of MRI also increased from 25.41% in 2005 to 36.02% in 2010. Among patients with TIA, use of CT increased from 84.64% to 88.04% and MRI from 32.53% to 39.13%. According to our results, female sex, younger age, and presence of comorbidities increase the likelihood of undergoing MRI.

Ostreid herpesvirus in wild oysters from the Huelva coast (SW Spain).

This is the first report of ostreid herpesvirus 1 microvariant (OsHV-1 µVar) infecting natural oyster beds located in Huelva (SW Spain). The virus was detected in 3 oyster species present in the intertidal zone: Crassostrea gigas (Thunberg, 1793), C. angulata (Lamarck, 1819) and, for the first time, in Ostrea stentina Payraudeau, 1826. Oysters were identified by a specific polymerase chain reaction (PCR) and posterior restriction fragment length polymorphism (RFLP) analysis based on cytochrome oxidase I (COI) mitochondrial DNA. Results confirmed that C. angulata still remains the dominant oyster population in SW Spain despite the introduction of C. gigas for cultivation in the late 1970s, and its subsequent naturalization. C. angulata shows a higher haplotype diversity than C. gigas. OsHV-1 virus was detected by PCR with C2/C6 pair primers. Posterior RFLP analyses with the restriction enzyme MfeI were done in order to reveal the OsHV-1 µVar. Detections were confirmed by DNA sequencing, and infections were evidenced by in situ hybridization in C. gigas, C. angulata and O. stentina samples. The prevalence was similar among the 3 oyster species but varied between sampling locations, being higher in areas with greater harvesting activities. OsHV-1 µVar accounted for 93% of all OsHV-1 detected.

Probing non polar interstellar molecules through their protonated form: Detection of protonated cyanogen (NCCNH+).

Cyanogen (NCCN) is the simplest member of the series of dicyanopolyynes. It has been hypothesized that this family of molecules can be important constituents of interstellar and circumstellar media, although the lack of a permanent electric dipole moment prevents its detection through radioastronomical techniques. Here we present the first solid evidence of the presence of cyanogen in interstellar clouds through the detection of its protonated form toward the cold dark clouds TMC-1 and L483. Protonated cyanogen (NCCNH+) has been identified through the J = 5 - 4 and J = 10 - 9 rotational transitions using the 40m radiotelescope of Yebes and the IRAM 30m telescope. We derive beam averaged column densities for NCCNH+ of (8.6 ± 4.4) × 1010 cm-2 in TMC-1 and (3.9 ± 1.8) × 1010 cm-2 in L483, which translate to fairly low fractional abundances relative to H2, in the range (1-10) × 10-12. The chemistry of protonated molecules in dark clouds is discussed, and it is found that, in general terms, the abundance ratio between the protonated and non protonated forms of a molecule increases with increasing proton affinity. Our chemical model predicts an abundance ratio NCCNH+/NCCN of ~ 10-4, which implies that the abundance of cyanogen in dark clouds could be as high as (1-10) × 10-8 relative to H2, i.e., comparable to that of other abundant nitriles such as HCN, HNC, and HC3N.

Desmontaje por efecto cut-out en el enclavado de fracturas pertrocantéreas de fémur: ¿cuál es el tratamiento de rescate de elección? / Removal due to cut-out effect in pertrochanteric femoral fractures: what is the rescue treatment of choice?

Objetivo. Comparar los resultados funcionales de las distintas opciones terapéuticas, y analizar los factores técnicos asociados al cut-out. Material y método. Estudio de cohortes retrospectivo de 56 pacientes diagnosticados de cut-out entre 2000-2010, divididos en dos grupos en función del tratamiento de rescate: artroplastia frente a conservar la cabeza femoral (alternativo). Se analizaron datos demográficos, características de la fractura y osteosíntesis, tip to apex distance (TAD), seguimiento, complicaciones y capacidad funcional final. Resultados. Grupo artroplastia 36 pacientes (64,28%) y 20 (35,72%) grupo alternativo. Comparables en parámetros demográficos, comorbilidades, patrón de fractura y características de la osteosíntesis. Se observó poca variabilidad interobservador (k = 0,83; IC 95%: 0,78-0,88) en el análisis radiográfico; con un TAD medio de 28,66 mm (p = 0,01) y un déficit de reducción en el 39,3% (p = 0,001). La mediana de cut-out fue de 60 días (artroplastia 90, alternativo 18; p = 0,001). Seguimiento mínimo 12 meses, con tasa de complicaciones similar en ambos grupos (p = 0,16) y de reintervención del 3,57% (p = 0,01). La capacidad funcional final fue mayor en el grupo de artroplastia (p = 0,004). Conclusión. El tratamiento de rescate con artroplastia ofrece mejores resultados funcionales, considerándolo el tratamiento de elección en pacientes ancianos, aunque la tasa de reintervención es mayor. Recomendamos nuevo enclavado antes que artroplastia en los casos de cut-out temprano (< 4 semanas) en aquellos casos que se mantenga la integridad de la cabeza femoral. Un déficit de reducción de la fractura es el principal factor predictor de fallo a corto plazo; un TAD por encima de 20 mm lo es a medio-largo plazo (AU)

Objective. The goal of the study was to compare functional results in different treament options in cutting-out, and analize factors associated to failure. Material and methods. Retrospective cohort study in 56 patients diagnosed with cutting-out between 2000-2010. Groups were based on rescue treatment: arthroplasty versus alternative treatment. Demographics, fracture characteristics, osteosynthesis, tip to apex distance (TAD), follow-up, complications, and final functional capacity were analyzed. Results. Rescue treatment: 36 (64.28%) hip replacement (arthroplasty group), and 20 (35.72%) alternative treatment preserving femoral head (alternative group). Groups comparable on demographic parameters, fracture pattern and osteosynthesis characteristics. Radiography analysis: low inter-observer variability (k = 0.83, 95% CI 0.78-0.88), mean TAD 28.66 mm (arthroplasty group 32.9 mm, 21.5 mm control group; p = 0.01), insufficient fracture reduction 39.3% (p = 0.001). Cutting-out diagnosis median 60 days (arthroplasty group 90 days, 18 days alternative group; p = 0.001). Follow up at least 12 months from rescue treatment. Similar complications rate in both groups (p = 0.16). Re-operation rate 3.57% (11.7% arthroplasty group, alternative group 0%; p = 0.01). Better final functional capacity in arthroplasty group (p = 0.004). Discussion. Hip arthroplasty offers better results, being considered the gold standard in geriatric patients, although re-operation rate is higher. We recommend new nailing before arthroplasty in early failure (4 weeks) in patients with femoral head integrity. An insufficient fracture reduction is the main short term factor predicting failure; and TAD higher than 20 mm is a middle-long term one (AU)

[Removal due to cut-out effect in pertrochanteric femoral fractures: what is the rescue treatment of choice?]. / Desmontaje por efecto cut-out en el enclavado de fracturas pertrocantéreas de fémur: ¿cuál es el tratamiento de rescate de elección?

OBJECTIVE: The goal of the study was to compare functional results in different treament options in cutting-out, and analize factors associated to failure. MATERIAL AND METHODS: Retrospective cohort study in 56 patients diagnosed with cutting-out between 2000-2010. Groups were based on rescue treatment: arthroplasty versus alternative treatment. Demographics, fracture characteristics, osteosynthesis, tip to apex distance (TAD), follow-up, complications, and final functional capacity were analyzed. RESULTS: Rescue treatment: 36 (64.28%) hip replacement (arthroplasty group), and 20 (35.72%) alternative treatment preserving femoral head (alternative group). Groups comparable on demographic parameters, fracture pattern and osteosynthesis characteristics. Radiography analysis: low inter-observer variability (k=0.83, 95% CI 0.78-0.88), mean TAD 28.66mm (arthroplasty group 32.9mm, 21.5mm control group; p=0.01), insufficient fracture reduction 39.3% (p=0.001). Cutting-out diagnosis median 60 days (arthroplasty group 90 days, 18 days alternative group; p=0.001). Follow up at least 12 months from rescue treatment. Similar complications rate in both groups (p=0.16). Re-operation rate 3.57% (11.7% arthroplasty group, alternative group 0%; p=0.01). Better final functional capacity in arthroplasty group (p=0.004). DISCUSSION: Hip arthroplasty offers better results, being considered the gold standard in geriatric patients, although re-operation rate is higher. We recommend new nailing before arthroplasty in early failure (4 weeks) in patients with femoral head integrity. An insufficient fracture reduction is the main short term factor predicting failure; and TAD higher than 20mm is a middle-long term one.