Identifying and optimizing human endometrial gene expression signatures for endometrial dating.

STUDY QUESTION: What are the key considerations for developing an enhanced transcriptomic method for secretory endometrial tissue dating? SUMMARY ANSWER: Multiple gene expression signature combinations can serve as biomarkers for endometrial dating, but their predictive performance is variable and depends on the number and identity of the genes included in the prediction model, the dataset characteristics and the technology employed for measuring gene expression. WHAT IS KNOWN ALREADY: Among the new generation of transcriptomic endometrial dating (TED) tools developed in the last decade, there exists variation in the technology used for measuring gene expression, the gene makeup and the prediction model design. A detailed study, comparing prediction performance across signatures for understanding signature behaviour and discrepancies in gene content between them, is lacking. STUDY DESIGN, SIZE, DURATION: A multicentre prospective study was performed between July 2018 and October 2020 at five different centres from the same group of clinics (Spain). This study recruited 281 patients and finally included in the gene expression analysis 225 Caucasian patients who underwent IVF treatment. After preprocessing and batch effect filtering, gene expression measurements from 217 patients were combined with artificial intelligence algorithms (support vector machine, random forest and k-nearest neighbours) allowing evaluation of different prediction models. In addition, secretory-phase endometrial transcriptomes from gene expression omnibus (GEO) datasets were analysed for 137 women, to study the endometrial dating capacity of genes independently and grouped by signatures. This provided data on the consistency of prediction across different gene expression technologies and datasets. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial biopsies were analysed using a targeted TruSeq (Illumina) custom RNA expression panel called the endometrial dating panel (ED panel). This panel included 301 genes previously considered relevant for endometrial dating as well as new genes selected for their anticipated value in detecting the secretory phase. Final samples (n = 217) were divided into a training set for signature discovery and an independent testing set for evaluation of predictive performance of the new signature. In addition, secretory-phase endometrial transcriptomes from GEO were analysed for 137 women to study endometrial dating capacity of genes independently and grouped by signatures. Predictive performance among these signatures was compared according to signature gene set size. MAIN RESULTS AND THE ROLE OF CHANCE: Testing of the ED panel allowed development of a model based on a new signature of 73 genes, which we termed 'TED' and delivers an enhanced tool for the consistent dating of the secretory phase progression, especially during the mid-secretory endometrium (3-8 days after progesterone (P) administration (P + 3-P + 8) in a hormone replacement therapy cycle). This new model showed the best predictive capacity in an independent test set for staging the endometrial tissue in the secretory phase, especially in the expected window of implantation (average of 114.5 ± 7.2 h of progesterone administered; range in our patient population of 82-172 h). Published sets of genes, in current use for endometrial dating and the new TED genes, were evaluated in parallel in whole-transcriptome datasets and in the ED panel dataset. TED signature performance was consistently excellent for all datasets assessed, frequently outperforming previously published sets of genes with a smaller number of genes for dating the endometrium in the secretory phase. Thus, this optimized set exhibited prediction consistency across datasets. LARGE SCALE DATA: The data used in this study is partially available at GEO database. GEO identifiers GSE4888, GSE29981, GSE58144, GSE98386. LIMITATIONS, REASONS FOR CAUTION: Although dating the endometrial biopsy is crucial for investigating endometrial progression and the receptivity process, further studies are needed to confirm whether or not endometrial dating methods in general are clinically useful and to guide the specific use of TED in the clinical setting. WIDER IMPLICATIONS OF THE FINDINGS: Multiple gene signature combinations provide adequate endometrial dating, but their predictive performance depends on the identity of the genes included, the gene expression platform, the algorithms used and dataset characteristics. TED is a next-generation endometrial assessment tool based on gene expression for accurate endometrial progression dating especially during the mid-secretory. STUDY FUNDING/COMPETING INTEREST(S): Research funded by IVI Foundation (1810-FIVI-066-PD). P.D.-G. visiting scientist fellowship at Oxford University (BEFPI/2010/032) and Josefa Maria Sanchez-Reyes' predoctoral fellowship (ACIF/2018/072) were supported by a program from the Generalitat Valenciana funded by the Spanish government. A.D.-P. is supported by the FPU/15/01398 predoctoral fellowship from the Ministry of Science, Innovation and Universities (Spanish Government). D.W. received support from the NIHR Oxford Biomedical Research Centre. The authors do not have any competing interests to declare.

A nearby transiting rocky exoplanet that is suitable for atmospheric investigation.

Spectroscopy of transiting exoplanets can be used to investigate their atmospheric properties and habitability. Combining radial velocity (RV) and transit data provides additional information on exoplanet physical properties. We detect a transiting rocky planet with an orbital period of 1.467 days around the nearby red dwarf star Gliese 486. The planet Gliese 486 b is 2.81 Earth masses and 1.31 Earth radii, with uncertainties of 5%, as determined from RV data and photometric light curves. The host star is at a distance of ~8.1 parsecs, has a J-band magnitude of ~7.2, and is observable from both hemispheres of Earth. On the basis of these properties and the planet's short orbital period and high equilibrium temperature, we show that this terrestrial planet is suitable for emission and transit spectroscopy.

A multiplanet system of super-Earths orbiting the brightest red dwarf star GJ 887.

The closet exoplanets to the Sun provide opportunities for detailed characterization of planets outside the Solar System. We report the discovery, using radial velocity measurements, of a compact multiplanet system of super-Earth exoplanets orbiting the nearby red dwarf star GJ 887. The two planets have orbital periods of 9.3 and 21.8 days. Assuming an Earth-like albedo, the equilibrium temperature of the 21.8-day planet is ~350 kelvin. The planets are interior to, but close to the inner edge of, the liquid-water habitable zone. We also detect an unconfirmed signal with a period of ~50 days, which could correspond to a third super-Earth in a more temperate orbit. Our observations show that GJ 887 has photometric variability below 500 parts per million, which is unusually quiet for a red dwarf.

A giant exoplanet orbiting a very-low-mass star challenges planet formation models.

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.

A candidate super-Earth planet orbiting near the snow line of Barnard's star.

Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.

Agregado trióxido mineral y cemento pórtland expuestos a irrigantes endodóncicos: pH, conductividad y solubilidad / Mineral trioxide aggregate and portland cement exposed to endodontic irrigants: pH, conductivity, and solubility

Objetivo: El objetivo de este estudio fue determinar, el pH, la conductividad y la solubilidad al someter el agregado trióxido mineral (MTA) y el cemento Pórtland (CP) a diferentes irrigantes utilizados en endodoncia. Material y Métodos: Se estudiaron un total de 210 muestras, 105 de cemento ProRoot MTA(R) blanco y 105 de CP blanco. Se seleccionaron los siguientes irrigantes: hipoclorito sódico al 2,5% y al 5%, ácido cítrico al 10% y al 20%, clorhexidina al 2%, EDTA al 17%, y suero fisiológico como control. Se expusieron 15 muestras de MTA y 15 de CP a cada tipo de irrigante. Se midieron los resultados a 1, 5, 15, 30 y 60 minutos. Resultados: La mayoría de cambios del pH y la conductividad fueron de pequeña magnitud, aunque estadísticamente significativos. Destacan la alcalinización del suero fisiológico y la acidificación del hipoclorito sódico. Con MTA disminuye la conductividad en hipoclorito sódico y aumenta la conductividad en EDTA. Con CP hubo una mayor pérdida de conductividad del hipoclorito sódico y del ácido cítrico. Todas las muestras disminuyeron el peso considerablemente después de la exposición a cualquiera de los irrigantes, y en general ésta fue mayor para el CP que el MTA. Conclusiones: El contacto del material de reparación con los irrigantes utilizados habitualmente en endodoncia altera poco el pH y la conductividad pero aumenta marcadamente su solubilidad. Estos cambios afectan menos al MTA que al CP

Objective. The aim of this study was to determine changes to pH, conductivity, and solubility when mineral trioxide aggregate (MTA) and Portland cement (PC) are exposed to different endodontic irrigants. Methods. The study included a total of 210 samples, 105 white ProRoot MTA® cement and 105 white PC cement. The following irrigants were tested: 2.5% and 5% sodium hypochlorite, 10% and 20% citric acid, 2% chlorhexidine, 17% ethylenediamine tetra-acetic acid (EDTA), and physiological serum as a control. Fifteen samples of each material were exposed to each irrigant. PH, conductivity, and solubility were measured at baseline and after 1, 5, 15, 30 and 60 minutes exposure to irrigants. Results. Most changes in pH and conductivity were of small magnitude, although statistically significant. For MTA and PC physical serum produced alkalinization, while sodium hypochlorite produced acidification. MTA lost conductivity when exposed to sodium hypochlorite but this increased with exposure to EDTA. PC underwent greater losses of conductivity when exposed to sodium hypochlorite and citric acid. All samples decreased in weight significantly after exposure to any of the irrigants, and the loss was generally greater for PC than MTA. Conclusions. When repair materials are exposed to the irrigants normally used in endodontics, pH levels and conductivity alter slightly, while solubility increases markedly. These effects were greater for PC than MTA

Rugosidad superficial del agregado de trióxido mineral y el cemento pórtland expuestos a irrigantes endodóncicos / Surface roughness of the mineral trioxide aggregate and Portland cement exposed to endodontic irrigants

Objetivo: El propósito de este estudio fue determinar la rugosidad superficial, al someter al agregado de trióxido mineral (MTA) y al cemento Pórtland (CP) a diferentes irrigantes utilizados en endodoncia. Material y Métodos: Se estudiaron un total de 210 muestras, 105 de cemento ProRoot MTA® blanco y 105 de CP blanco. Se seleccionaron los siguientes irrigantes: hipoclorito sódico al 2,5% y al 5%, ácido cítrico al 10% y al 20%, clorhexidina al 2%, EDTA al 17%, y suero fisiológico como control. Se expusieron 15 muestras de cada cemento por cada tipo de irrigante durante 15 minutos. El estudio de la rugosidad superficial se hizo con el microscopio Leica DCM 3D que permite una perfilometría con tecnología dual confocal e interferométrica. Se evaluó la rugosidad media (Ra), el valor cuadrático medio (RMS) y la profundidad de rugosidad máxima (PV) al inicio y a los 15 minutos de la inmersión de las muestras. Resultados: El CP aumentó significativamente la rugosidad en los parámetros Ra y RMS tras la irrigación con hipoclorito al 2,5%, ácido cítrico al 10% y al 20%, y suero fisiológico. En términos de PV el CP solo aumentó la rugosidad tras la irrigación con ácido cítrico al 20% y suero fisiológico. El MTA no mostró cambios significativos respecto a la rugosidad Ra, RMS y PV con ninguno de los irrigantes. Conclusiones: La rugosidad superficial del CP puede modificarse por la exposición a alguno de los irrigantes utilizados en endodoncia, mientras que la rugosidad del MTA no se modifica significativamente

Objectives: This study set out to determine changes to surface roughness when mineral trioxide aggregate (MTA) and Portland cement (PC) are exposed to the different irrigants used in endodontics. Material and Methods: The study included a total of 210 samples, 105 white ProRoot MTA® cement and 105 white PC cement. The following irrigants were tested: 2.5% and 5% sodium hypochlorite, 10% and 20% citric acid, 2% chlorhexidine, 17% ethylenediamine tetra-acetic acid (EDTA), and physiological serum as a control. Fifteen samples of each material were exposed to each irrigant for 15 minutes. Surface roughness evaluation was performed using a Leica DCM 3D microscope for dual system (confocal and interferometric) profilometry. Mean roughness (Ra), root mean square (RMS) and maximum roughness depth (PV) were evaluated before and after 15 minutes sample immersion in each irrigant. Results: PC significantly increased roughness for Ra and RMS parameters after irrigation with 2.5% sodium hypochlorite, 10% and 20% citric acid, and physiological serum. PC underwent an increase in the PV parameter after immersion in 20% citric acid and physiological serum. MTA did not show significant changes in Ra, RMS or PV with any of the irrigants. Significance. The surface roughness of PC may be modified by exposure to some of the irrigants used in endodontics, while the roughness of MTA is not modified significantly

A phase II randomized study evaluating the addition of iniparib to gemcitabine plus cisplatin as first-line therapy for metastatic non-small-cell lung cancer.

BACKGROUND: Iniparib is a novel anticancer agent initially considered a poly (ADP-ribose) polymerase (PARP) inhibitor, but subsequently shown to act via non-selective protein modification through cysteine adducts. This randomized phase II study investigated the addition of iniparib to gemcitabine-cisplatin in metastatic non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Patients with histologically confirmed stage IV NSCLC were randomized 2 : 1 to receive gemcitabine (1250 mg/m(2), days 1/8) and cisplatin (75 mg/m(2), day 1) with [gemcitabine/cisplatin/iniparib (GCI)] or without [gemcitabine/cisplatin (GC)] iniparib (5.6 mg/kg, days 1/4/8/11) every 3 weeks for six cycles. The primary end point was the overall response rate (ORR). Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety. The study was not designed for formal efficacy comparison, the control arm being to benchmark results against the literature. RESULTS: One hundred and nineteen patients were randomized (39 GC and 80 GCI). More GCI patients were male (80% GCI and 67% GC) and had PS 0 (61% GCI and 49% GC). The ORR was 25.6% [95% confidence interval (CI) 13.0%-42.1%] with GC versus 20.0% (95% CI 11.9%-30.4%) with GCI, which did not allow rejection of the null hypothesis (ORR with GCI ≤20%; P = 0.545). Median PFS was 4.3 (95% CI 2.8-5.6) months with GC and 5.7 (95% CI 4.6-6.6) months with GCI (hazard ratio 0.89, 95% CI 0.56-1.40). Median OS was 8.5 (95% CI 5.5 to not reached) months with GC, and 12.0 (95% CI 8.9-17.1) months with GCI (hazard ratio 0.78, 95% CI 0.48-1.27). More GCI patients received second-line treatment (51% GC and 68% GCI). Toxicity was similar in the two arms. Grade 3-4 toxicities included asthenia (28% GC and 8% GCI), nausea (3% GC and 14% GCI), and decreased appetite (10% in each). CONCLUSIONS: Addition of iniparib to GC did not improve ORR over GC alone. The GCI safety profile was comparable to GC alone. Imbalances in PS and gender distribution may have impacted study results regarding PFS and OS. TRIAL REGISTRATION: ClinicalTrial.gov Identifier NCT01086254.

A Be-type star with a black-hole companion.

Stellar-mass black holes have all been discovered through X-ray emission, which arises from the accretion of gas from their binary companions (this gas is either stripped from low-mass stars or supplied as winds from massive ones). Binary evolution models also predict the existence of black holes accreting from the equatorial envelope of rapidly spinning Be-type stars (stars of the Be type are hot blue irregular variables showing characteristic spectral emission lines of hydrogen). Of the approximately 80 Be X-ray binaries known in the Galaxy, however, only pulsating neutron stars have been found as companions. A black hole was formally allowed as a solution for the companion to the Be star MWC 656 (ref. 5; also known as HD 215227), although that conclusion was based on a single radial velocity curve of the Be star, a mistaken spectral classification and rough estimates of the inclination angle. Here we report observations of an accretion disk line mirroring the orbit of MWC 656. This, together with an improved radial velocity curve of the Be star through fitting sharp Fe II profiles from the equatorial disk, and a refined Be classification (to that of a B1.5-B2 III star), indicates that a black hole of 3.8 to 6.9 solar masses orbits MWC 656, the candidate counterpart of the γ-ray source AGL J2241+4454 (refs 5, 6). The black hole is X-ray quiescent and fed by a radiatively inefficient accretion flow giving a luminosity less than 1.6 × 10(-7) times the Eddington luminosity. This implies that Be binaries with black-hole companions are difficult to detect in conventional X-ray surveys.

Impact on patient care time and tumor stage of a program for fast diagnostic and treatment of colorectal cancer.

OBJECTIVES: To evaluate the effectiveness of a fast track diagnosis and treatment program for colorectal cancer (CRC) in reducing the diagnosis to treatment interval (DTI) and tumor stage. To analyze the association between DTI and tumor stage. METHODS: A quasi-experimental study with a control group was conducted, and 156 incident cases of CRC referred through a preferential pathway between July 2005 and December 2008 in a tertiary hospital were included, after excluding those treated urgently, treated by endoscopic polypectomy only or having periodic colonoscopies. A control group of 156 patients was randomly selected from all the patients referred through habitual pathways, frequency matched by tumor location, age and year of entry. Data was analyzed with multivariate linear and logistic regression. RESULTS: Mean DTI was 39.20 days (95% CI: 36.21-42.42) for fast track patients and 63.40 days (95% CI: 57.08-70.41) for controls (p < 0.001), and this difference persisted after multivariate analysis. The odds of having a DTI longer than 30 days was 4.79 (95% CI: 2.19-10.51) higher for controls. There were no significant differences in tumor stage according to the pathway followed. Independently of the track followed, a DTI longer than 30 days was associated with advanced tumor stages for colon cancer, while it was associated with low stages for rectal cancer. CONCLUSIONS: The PDTR strategy is effective in reducing DTI and may reduce patients' and relatives' anxiety. However, it is far from reaching the DTI recommended. The achieved reduction of the delay has no impact on tumor stage.

Impacto en el tiempo asistencial y el estadio tumoral de un programa de diagnóstico y tratamiento rápido del cáncer colorrectal / No disponible

Objetivos: evaluar la efectividad de un programa de diagnóstico y tratamiento rápido (PDTR) del cáncer colorrectal (CCR) en la reducción del intervalo diagnóstico-terapéutico (IDT) y el estadio tumoral. Analizar la asociación entre IDT y estadio tumoral. Métodos: estudio cuasiexperimental con grupo control en el que se incluyeron 156 casos incidentes de CCR atendidos por el PDTR entre julio de 2005 y diciembre de 2008 en un hospital de tercer nivel, tras excluir los que requirieron tratamiento urgente, tratados solo por polipectomía endoscópica o con colonoscopías periódicas. Un grupo control de 156 pacientes fue seleccionado al azar de los atendidos por el circuito habitual con la misma localización tumoral, edad y año de ingreso. Para el análisis se utilizó regresión lineal y logística. Resultados: la media del IDT fue de 39,20 días (IC 95%: 36,21-42,42) en los pacientes del programa y de 63,40 días (IC 95%: 57,08-70,41) en el grupo control (p < 0,001); esta diferencia se mantuvo en el análisis multivariado. La probabilidad de un IDT mayor de 30 días fue 4,79 (IC 95%: 2,19-10,51) veces superior en los controles. No se encontraron diferencias significativas en el estadio tumoral según el circuito asistencial. Independientemente del circuito, un IDT > 30 días se asoció con un estadio tumoral avanzado en los tumores de colon, mientras que en los de recto se asoció con estadios precoces. Conclusiones: el PDTR es efectivo reduciendo los tiempos asistenciales y con ello seguramente reduce la angustia de pacientes y familiares. No obstante, está lejos de alcanzar el IDT recomendado. La reducción de la demora conseguida no tiene impacto en el estadio tumoral(AU)

Objectives: to evaluate the effectiveness of a fast track diagnosis and treatment program for colorectal cancer (CRC) in reducing the diagnosis to treatment interval (DTI) and tumor stage. To analyze the association between DTI and tumor stage. Methods: a quasi-experimental study with a control group was conducted, and 156 incident cases of CRC referred through a preferential pathway between July 2005 and December 2008 in a tertiary hospital were included, after excluding those treated urgently, treated by endoscopic polypectomy only or having periodic colonoscopies. A control group of 156 patients was randomly selected from all the patients referred through habitual pathways, frequency matched by tumor location, age and year of entry. Data was analyzed with multivariate linear and logistic regression. Results: mean DTI was 39.20 days (95% CI: 36.21-42.42) for fast track patients and 63.40 days (95% CI: 57.08-70.41) for controls (p < 0.001), and this difference persisted after multivariate analysis. The odds of having a DTI longer than 30 days was 4.79 (95% CI: 2.19-10.51) higher for controls. There were no significant differences in tumor stage according to the pathway followed. Independently of the track followed, a DTI longer than 30 days was associated with advanced tumor stages for colon cancer, while it was associated with low stages for rectal cancer. Conclusions: the PDTR strategy is effective in reducing DTI and may reduce patients’ and relatives’ anxiety. However, it is far from reaching the DTI recommended. The achieved reduction of the delay has no impact on tumor stage(AU)

Gemcitabine and oxaliplatin combination: a multicenter phase II trial in unfit patients with locally advanced or metastatic urothelial cancer.

BACKGROUND: Up to 50% of patients with bladder cancer cannot be treated with cisplatin because they are considered unfit due to poor renal function. Gemcitabine and oxaliplatin are active, nonnephrotoxic therapies with nonoverlapping toxicity profiles that provide an alternative therapy for this group of patients. PATIENTS AND METHODS: In a multicenter study, patients received gemcitabine 1200 mg/m(2) on days 1 and 8 and oxaliplatin 100 mg/m(2) on day 8 every 21 days. Eligible criteria were creatinine clearance >30 ml/min and/or Eastern Cooperative Oncology Group (ECOG) performance status of two or less. RESULTS: Forty-six patients were assessable for response and toxicity. Median age was 69 years (range 52-85), median ECOG two (range 0-2). Median number of metastatic sites was 2 (range 1-6). Median creatinine clearance was 50.73 ml/min (range 30-87). A total of 187 cycles were given with a median of 5 (range 1-6). Hematological toxicity was mild with grade 3-4 peripherical neuropathy occurring in 4% of patients. Overall response rate was 48% (three complete response, 19 partial response, seven stable disease and 17 progressive disease). Median time to disease progression was 5 months. CONCLUSION: Gemcitabine-oxaliplatin is an active and tolerable combination with response rate that merits further study in patients with impaired renal function but good performance status.

[Resistance to antiretroviral therapy]. / Resistencias al tratamiento antirretroviral.

OVERVIEW: After some time under treatment, HIV+ patients have a virologic failure rate of 50%, being development of resistance to therapy responsible for up to 80% of the virologic failure. In addition, resistance rates in naive patients is around 10% in developed countries. Inherent characteristics of HIV (replication cycle, viral subtype), of patients (therapy compliance, intra-/interindividual variability, genetic polymorphisms), and of therapy (genetic barrier to drug resistance, inhibitory ratio, drug interactions) are the factors involved in the development of resistance, and their interpretation requires to be studied. Resistance identification will be carried out using genotypical and/or phenotypical methods, and their adequacy has been validated by various expert panels on resistance. The role of the pharmacokinetic and pharmacodynamic monitoring of antiretroviral therapy is also crucial within the field of resistance, and concerns us directly as pharmacists. Finally, understanding the resistance patterns of currently available or experimental antiretroviral drug families will provide the necessary tools to prevent and/or manage their development. OBJECTIVES: To know and understand the mechanisms and patterns of resistance for each antiretroviral family. To identify factors involved in the development of resistance to ART, and to interpret various resistance tests. SEARCH STRATEGY: Studies were identified using Medline, the Cochrane database of systemic reviews, abstracts from international meetings on AIDS, Conference on Retroviruses and Opportunistic Infections, international meetings on resistance to antiretrovirals, and product monographs from January 1999 to February 2004. SELECTION CRITERIA: To be eligible, studies had to describe viral genome mutations responsible for resistance or hypersusceptibility to ART in relation to precipitating factors. Papers describing resistance identification techniques were also selected. DATA COLLECTION AND ANALYSIS: In all, 1,083 full articles and 64 abstracts and communications at international meetings were retrieved, of which 74 articles and 20 abstracts met the inclusion criteria for our review. PRIMARY RESULTS: Of the 94 reports selected, 86 discussed factors involved in the development of resistance and resistance test interpretation. The remaining 8 reports focused on resistance patterns to the various antiretroviral drug families. Every article described the enzymatic mechanisms induced by mutations responsible for resistance or hypersusceptibility to each antiretroviral family, the classification and nomenclature for each mutation, and the influence of each mutation on the success or failure of patient treatment. REVIEWER S CONCLUSIONS: Knowledge of the mechanisms and patterns of resistance to each antiretroviral family will allow us to overall understand the evolution and outcome of treatment for any given patient. Only thus shall we be able to play an integral role in the therapy of patients.

Salud maternoinfantil basada en la evidencia / No disponible

No disponible

[Patient discharge form in primary care (II): views and level of satisfaction of family doctors]. / El informe de alta hospitalaria en atención primaria (II): opiniones y satisfacción de los médicos de familia.

OBJECTIVE: To analyse the opinion and satisfaction shown by a sample of primary care (PC) doctors about the patient discharge form (PDF) and to assess proposals for improvement. Design. Descriptive study of the result of a questionnaire. SETTING: All the health districts in the city of Mataró (Barcelona).Participants. 37 PC doctors treating adults out of a total of 43 (86% participation). METHOD: Written questionnaire, self-answered and anonymous, filled in after a brief introduction. RESULTS: 73% of those surveyed were <> - <> with the PDF. 82.9% valued it positively as a nexus of union between PC and hospital. 38.9% of these did not obtain a response consonant with their prior expectations. The written comprehension and expression on medical PDFs was considered better than on surgical ones. The amount of information was <> from 70.3% of medical doctors as against 40.5% of surgeons. The filling-in of the various sections of the PDF were mainly valued as <> - <> (better in medical than surgical doctors). Most evaluated the information provided as <> - <>, mainly in the medical PDF. The main changes to be introduced refer to the treatment, post-discharge follow-up and the omission of social-health and nursing questions. CONCLUSIONS: A high percentage of those surveyed value the PDF highly as a nexus linking PC and Hospital, despite finding faults in the information contained. The PDF could become more useful if there was more dialogue between doctors at the two care levels.

Síndrome de secreción inadecuada de la hormona antidiurética como forma de presentación de un carcinoma microcítico de pulmón oculto / Syndrome of inappropiate secretion of antidiuretic hormone as the first manifestation of an occult small cell lung cancer

No disponible

El informe de alta hospitalaria en atención primaria (II): opiniones y satisfacción de los médicos de familia / Patient discharge form in primary care (II): views and level of satisfaction of family doctors

Objetivo. Analizar la opinión y satisfacción manifestadas por una muestra de médicos de atención primaria (AP) acerca del informe de alta hospitalaria (IAH) valorando propuestas de mejora. Diseño. Estudio descriptivo del resultado de una encuesta. Emplazamiento. La totalidad de las áreas básicas de salud de la ciudad de Mataró (Barcelona). Participantes. Treinta y siete médicos de adultos de AP de un total de 43 (86 per cent de participación). Método. Cuestionario escrito, rellenado por el encuestado y anónimo cumplimentado tras una breve presentación. Resultados. Un 73 per cent de los encuestados se muestra muy satisfecho-satisfecho con el IAH. El 82,9 per cent lo considera positivo como nexo entre la AP y el hospital. El 38,9 per cent de éstos no obtiene respuesta a sus expectativas previas. La comprensión y expresión escrita fue mejor valorada en los IAH médicos que en los quirúrgicos. La cantidad de información fue suficiente en el 70,3 per cent de los médicos frente al 40,5 per cent de los quirúrgicos. El grado de cumplimentación de los diversos apartados del IAH se estimaron mayoritariamente como muy buenos-buenos (mejor en médicos que quirúrgicos). La mayoría consideró que la información proporcionada era muy útilútil, principalmente en los IAH médicos. Las principales modificaciones a introducir hacen referencia al tratamiento, al seguimiento postalta y a la falta de mención a aspectos sociosanitarios y de enfermería. Conclusiones. Un elevado porcentaje de los encuestados considera positivo el IAH como nexo entre la AP y el hospital, a pesar de encontrar deficiencias en su contenido informativo. Un mayor diálogo entre los profesionales de los dos niveles asistenciales permitiría mejorar la utilidad del IAH. (AU)

Prenatal and postnatal characterization of Y chromosome structural anomalies by molecular cytogenetic analysis.

We describe three cases in which we used fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) and comparative genomic hybridization (CGH) to characterize Y chromosome structural anomalies, unidentifiable by conventional G-banding. Case 1 was a 46,X,+mar karyotype; FISH analysis revealed an entire marker chromosome highlighted after hybridization with the Y chromosome painting probe. The PCR study showed the presence of Y chromosome markers AMG and SY620 and the absence of SY143, SY254 and SY147. CGH results confirmed the loss of Yq11.2-qter. These results indicated the presence of a deletion: del(Y)(q11.2). Case 2 was a 45,X [14]/46,XY[86] karyotype with a very small Y chromosome. The PCR study showed the presence of Y chromosome markers SY620 and AMG, and the absence of SY143, SY254 and SY147. CGH results showed gain of Yq11.2-pter and loss of Yq11.2-q12. These results show the presence of a Yp isodicentric: idic(Y)(q11.2). Case 3 was a 45,X,inv(9)(p11q12)[30]/46,X,idic(Y)(p11.3?),inv(9)(p11q12)[70] karyotype. The FISH signal covered all the abnormal Y chromosome using a Y chromosome paint. The PCR study showed the presence of Y chromosome markers AMG, SY620, SY143, SY254 and SY147. CGH only showed gain of Yq11.2-qter. These results support the presence of an unbalanced (Y;Y) translocation. Our results show that the combined use of molecular and classical cytogenetic methods in clinical diagnosis may allow a better delineation of the chromosome regions implicated in specific clinical disorders.

Alteraciones gastrointestinales en corredores de fondo / Gastrointestinal disturbances in long distance runners

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