Atrial fibrillation ablation in patients with arrhythmia-induced cardiomyopathy: a prospective multicentre study.

AIMS: This study aims to investigate the clinical and biochemical characteristics of patients with atrial fibrillation (AF) referred for ablation who develop arrhythmia-induced cardiomyopathy (AiCM) as well as their long-term outcomes after catheter ablation (CA). METHODS AND RESULTS: A prospective multicentre study was conducted on consecutive AF patients who underwent CA. AiCM was defined as the development of heart failure in the presence of AF and an improvement of left ventricular fraction by at least 10% at 6 months after ablation. A subgroup of patients underwent peripheral and left atrial blood samples [galectin-3, fatty acid-binding protein 4 (FABP4), and soluble receptor for advanced glycation end products (sRAGE)] at the time of the procedure. Of the 769 patients who underwent AF ablation, 135 (17.56%) met the criteria for AiCM. Independent predictors of AiCM included persistent AF, male gender, left atrial volume, QRS width, active smoking, and chronic kidney disease (CKD). Biomarker analysis revealed that sRAGE, FABP4, and galectin-3 levels were not predictive of AiCM development nor did they differ between groups or predict recurrence. There were no differences in AF recurrence between patients with and without AiCM (30.83% vs. 27.77%; P = 0.392) during a median follow-up of 23.83 months (inter-quartile range 9-36). CONCLUSIONS: In the subset of patients referred for AF ablation, the development of AiCM was associated with persistent AF and CKD. Biomarker analysis was not different between groups nor predicted recurrence. Patients with AiCM benefited from ablation, with a significant improvement in left ventricular ejection fraction and similar AF recurrence rates to those without AiCM.

Predictive Model and Risk Score for In-Hospital Mortality in Patients with All-Cause Cardiogenic Shock.

Cardiogenic shock (CS) is a condition associated with high morbidity and mortality. Our study aimed to perform a risk score for in-hospital mortality that allows for stratifying the risk of death in patients with CS.This is a retrospective analysis, which included 135 patients from a Spanish university hospital between 2011 and 2020. The Santiago Shock Score (S3) was created using clinical, analytical, and echocardiographic variables obtained at the time of admission.The in-hospital mortality rate was 41.5%, and acute coronary syndrome (ACS) was the responsible cause of shock in 60.7% of patients. Mitral regurgitation grade III-IV, age, ACS etiology, NT-proBNP, blood hemoglobin, and lactate at admission were included in the score. The S3 had good accuracy for predicting in-hospital mortality area under the receiver operating characteristic curve (AUC) 0.85 (95% confidence interval (CI) 0.78-0.90), higher than the AUC of the CardShock score, which was 0.74 (95% CI 0.66-0.83). Predictive power in a cohort of 131 patients with profound CS was similar to that of CardShock with an AUC of 0.601 (95% CI 0.496-0.706) versus an AUC of 0.558 (95% CI 0.453-0.664). Three risk categories were created according to the S3: low (scores 0-6), intermediate (scores 7-10), and high (scores 11-16) risks, with an observed mortality of 12.9%, 49.1%, and 87.5% respectively (P < 0.001).The S3 score had excellent predictive power for in-hospital mortality in patients with nonprofound CS. It could aid the initial risk stratification of patients and thus, guide treatment and clinical decision making in patients with CS.

Assessing the impact of SARS-CoV-2 lineages and mutations on patient survival

After more than two years of COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations whose impact on COVID-19 severity and patient survival is uncertain. A total of 764 SARS-CoV-2 genomes sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30st April 2021, along with their clinical data, were used for survival analysis. A significant association of B.1.1.7, the alpha lineage, with patient mortality (Log Hazard ratio LHR=0.51, C.I.=[0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome rendered 27 of them significantly associated with higher mortality of patients. Most of these mutations were located in the S, ORF8 and N proteins. This study illustrates how a combination of genomic and clinical data provide solid evidence on the impact of viral lineage on patient survival.

Early angiography in elderly patients with non-ST-segment elevation acute coronary syndrome: The cardio CHUS-HUSJ registry.

BACKGROUND: In elderly patients with non-ST elevation acute coronary syndrome (NSTEACS), while routine invasive management is established in high-risk NSTEACS patients, there is still uncertainty regarding the optimal timing of the procedure. METHODS: This study analyzes the association of early coronary angiography with all-cause mortality, cardiovascular mortality, heart failure (HF) hospitalization, and major adverse cardiovascular events (MACE) in patients older than 75 years old with NSTEACS. This retrospective observational study included 7811 consecutive NSTEACS patients who were examined between the years 2003 and 2017 at two Spanish university hospitals. There were 2290 patients older than 75 years old. We compared their baseline characteristics according to the early invasive strategy used (coronarography ≤24 h vs. coronarography >24 h) after the diagnosis of NSTEACS. RESULTS: Among the study participants, 1566 patients (68.38%) underwent early invasive coronary intervention. The mean follow-up period was 46 months (interquartile range 18-71 months). This association was also maintained after propensity score matching: early invasive strategy was significantly related to lower all-cause mortality [HR 0.61 (95% CI 0.51-0.71)], cardiovascular mortality [HR 0.52 (95% CI 0.43-0.63)], and MACE [HR 0.62 (CI 95% 0.54-0.71)]. CONCUSIONS: In a contemporary real-world registry of elderly NSTEACS patients, early invasive management significantly reduced all-cause mortality, cardiovascular mortality, and MACE during long-term follow-up. BRIEF SUMMARY: In this real-world retrospective observational study that included 2451 patients older than 75 years old, 1566 patients (68.38%) underwent early invasive coronary intervention. After performing a propensity score matching, the early invasive strategy was still associated with lower all-cause mortality [HR (hazard ratio) 0.61, 95% CI (95% confidence interval) (0.51-0.71)], cardiovascular mortality [HR 0.52 (95%CI 0.43-0.63)], and MACE [HR 0.62 (95%CI 0.54-0.71)] during long-term follow-up.

New susceptibility loci for severe COVID-19 by detailed GWAS analysis in European populations

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic [~]0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.

From partial to whole genome imputation of SARS-CoV-2 for epidemiological surveillance

Backgroundthe current SARS-CoV-2 pandemic has emphasized the utility of viral whole genome sequencing in the surveillance and control of the pathogen. An unprecedented ongoing global initiative is increasingly producing hundreds of thousands of sequences worldwide. However, the complex circumstances in which viruses are sequenced, along with the demand of urgent results, causes a high rate of incomplete and therefore useless, sequences. However, viral sequences evolve in the context of a complex phylogeny and therefore different positions along the genome are in linkage disequilibrium. Therefore, an imputation method would be able to predict missing positions from the available sequencing data. ResultsWe developed impuSARS, an application that includes Minimac, the most widely used strategy for genomic data imputation and, taking advantage of the enormous amount of SARS-CoV-2 whole genome sequences available, a reference panel containing 239,301 sequences was built. The impuSARS application was tested in a wide range of conditions (continuous fragments, amplicons or sparse individual positions missing) showing great fidelity when reconstructing the original sequences. The impuSARS application is also able to impute whole genomes from commercial kits covering less than 20% of the genome or only from the Spike protein with a precision of 0.96. It also recovers the lineage with a 100% precision for almost all the lineages, even in very poorly covered genomes (< 20%) Conclusionsimputation can improve the pace of SARS-CoV-2 sequencing production by recovering many incomplete or low-quality sequences that would be otherwise discarded. impuSARS can be incorporated in any primary data processing pipeline for SARS-CoV-2 whole genome sequencing.

Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality

BackgroundThere is considerable variability in COVID-19 outcomes amongst younger adults--and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. MethodThe major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. FindingsWe found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1{middle dot}4, 95% confidence interval [CI] 1{middle dot}2-1{middle dot}6) and COVID-19 related mortality (HR 1{middle dot}5, 95%CI 1{middle dot}3-1{middle dot}8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2{middle dot}0, 95%CI 1{middle dot}6-2{middle dot}6), venous thromboembolism (OR 1{middle dot}7, 95%CI 1{middle dot}2-2{middle dot}4), and hepatic injury (OR 1{middle dot}6, 95%CI 1{middle dot}2-2{middle dot}0). Risk allele carriers [≤] 60 years had higher odds of death or severe respiratory failure (OR 2{middle dot}6, 95%CI 1{middle dot}8-3{middle dot}9) compared to those > 60 years OR 1{middle dot}5 (95%CI 1{middle dot}3-1{middle dot}9, interaction p-value=0{middle dot}04). Amongst individuals [≤] 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31{middle dot}8% (95%CI 27{middle dot}6-36{middle dot}2) were risk variant carriers, compared to 13{middle dot}9% (95%CI 12{middle dot}6-15{middle dot}2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those [≤] 60 years improved when including the risk allele (AUC 0{middle dot}82 vs 0{middle dot}84, p=0{middle dot}016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. InterpretationThe major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality--and these are more pronounced amongst individuals [≤] 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management. FundingFunding was obtained by each of the participating cohorts individually.

Sample Pooling as an efficient strategy for SARS-COV-2 RT-PCR screening: a multicenter study in Spain

ImportanceThe actual demand on SARS-CoV-2 diagnosis is a current challenge for clinical laboratories. Sample pooling may help to ameliorate workload in clinical laboratories. Objectiveto evaluate the efficacy of sample pooling compared to the individual analysis for the diagnosis of CoVID-19, by using different commercial platforms for nucleic acid extraction and amplification. Design and settingsobservational, prospective, multicentre study across 9 Spanish clinical microbiology laboratories including SARS-CoV-2 RNA testing performed in April 2020, during the first three days after acceptance to participate. Participants and Methods3519 naso-oro-pharyngeal samples received at the participating laboratories were processed individually and in pools (351 pools) according to the existing methodology in each of the centres. ResultsWe found that 253 pools (2519 samples) were negative, and 99 pools (990 samples) were positive; with 241 positive samples (6.85%), our pooling strategy would have saved 2167 PCR tests. For 29 pools (made out of 290 samples) we found discordant results when compared to their correspondent individual samples: in 24/29 pools (30 samples), minor discordances were found; for five pools (5 samples), we found major discordances. Sensitivity, specificity, positive and negative predictive values for pooling were 97.93%, 100%, 100% and 99.85% respectively; accuracy was 99.86% and kappa concordant coefficient was 0.988. As a result of the sample dilution effect of pooling, a loss of 2-3 Cts was observed for E, N or RdRP genes. Conclusionwe show a high efficiency of pooling strategies for SARS-CoV-2 RNA testing, across different RNA extraction and amplification platforms, with excellent performance in terms of sensitivity, specificity, and positive and negative predictive values. We believe that our results may help clinical laboratories to respond to the actual demand and clinical need on SARS-CoV-2 testing, especially for the screening of low prevalence populations. Key points QuestionMay clinical laboratories implement sample pooling as an efficient and safe strategy for SARS-COV-2 RT-PCR screening? FindingsSensitivity, specificity, positive and negative predictive values for pooling were 97.93%, 100%, 100% and 99.85% respectively; accuracy was 99.86% and kappa concordant coefficient was 0.988. MeaningSample pooling can be used safely at clinical laboratories, especially for the screening of low prevalence populations.

Hepatitis C virus core antigen in the management of patients treated with new direct-acting antivirals.

We evaluated the utility of Architect core antigen assay® Abbott Diagnostics (HCVAg) for monitoring patients with HCV infection and compared to HCV-RNA quantification (Cobas Ampliprep TaqMan-Roche Diagnostics). Samples from 262 patients were studied. Mean baseline HCV RNA and HCVAg levels were similar for responders (6.2 log IU/mL and 3.4 log fmol/L) and non-responders (6.1 log IU/mL and 3.2 log fmol/L), respectively. Only 10 patients failed to achieve SVR12 and all were detected by both assays. To evaluate HCVAg quantification as a tool for the detection of failure to DAAs, we performed a retrospective study of 132 non-responder patients. Mean HCV RNA and HCVAg levels at the time of detection of therapeutic failure were 5.88±0.97 log IU/mL and 3.19±0.79 log fmol/L, respectively. HCVAg (>3 fmol/L) was detected in 130/132 patients (98.5%). HCVAg assay was useful for patient selection and for evaluating virological response to DAAs in the real world.

Bilateral Shoulder Dysfunction Related to the Lung Resection Area After Thoracotomy.

This study aimed to investigate the mobility, pain, and disability of the shoulders after different pulmonary surgical procedures.It is a cross-sectional prospective study. A total of 38 patients who underwent lung surgery via thoracotomy (mean age = 57 ±â€Š10 years) were evaluated in the preoperative period, and first and second postoperative days were assessed for range of motion of shoulder; pain intensity; and application of the Shoulder Pain and Disability Index questionnaire. This study compared the 3 days of evaluation, and the subgroups according to the resection area (biopsy/nodulectomy, lung segmentectomy and lobectomy).There was a decrease of flexion (153°â€Š±â€Š16°-98°â€Š±â€Š23°), abduction (151°â€Š±â€Š20°-126°â€Š±â€Š38°), and increased Shoulder Pain and Disability Index (2.4-44.3) in the shoulder ipsilateral to surgery from the preoperative to the first postoperative day (P < 0.05). There was a greater loss of ipsilateral flexion and abduction in the lobectomy subgroup (P < 0.05), and decreased abduction of the contralateral shoulder in the lung segmentectomy and lobectomy subgroups (P < 0.05).After pulmonary surgery, there is bilateral impairment in shoulder range of motion, with greater limitation on ipsilateral shoulder, and larger resections.

NIK controls classical and alternative NF-κB activation and is necessary for the survival of human T-cell lymphoma cells.

PURPOSE: Peripheral T-cell lymphomas (PTCL) are a heterogeneous entity of neoplasms with poor prognosis, a lack of effective therapies, and a largely unknown molecular pathology. Deregulated NF-κB activity has been associated with several lymphoproliferative diseases, but its importance in T-cell lymphomagenesis is poorly understood. We investigated the function of the NF-κB-inducing kinase (NIK), in this pathway and its role as a potential molecular target in T-cell lymphomas. EXPERIMENTAL DESIGN: We used immunohistochemistry to analyze the expression of different NF-κB members in primary human PTCL samples and to study its clinical impact. With the aim of inhibiting the pathway, we used genetic silencing of NIK in several T-cell lymphoma cell lines and observed its effect on downstream targets and cell viability. RESULTS: We showed that the NF-κB pathway was activated in a subset of PTCLs associated with poor overall survival. NIK was overexpressed in a number of PTCL cell lines and primary samples, and a pivotal role for NIK in the survival of these tumor cells was unveiled. NIK depletion led to a dramatic induction of apoptosis in NIK-overexpressing cell lines and also showed a more pronounced effect on cell survival than inhibitor of kappa B kinase (IKK) knockdown. NIK silencing induced a blockage of both classical and alternative NF-κB activation and reduced expression of several prosurvival and antiapoptotic factors. CONCLUSIONS: The results of the present study indicate that NIK could be a promising therapeutic target in these aggressive malignancies.

Homozygous deletion of an EGR2 enhancer in congenital amyelinating neuropathy.

The transcription factor EGR2 is expressed in Schwann cells, where it controls peripheral nerve myelination. Mutations of EGR2 have been found in patients with congenital hypomyelinating neuropathy or Charcot-Marie-Tooth disease type 1D. In a patient with congenital amyelinating neuropathy, we observed pathological abnormalities recapitulating the peripheral nervous system phenotype of homozygous Egr2-null mice. This patient, born from consanguineous parents, showed no EGR2 immunoreactivity in Schwann cells and harbored a homozygous 10.7-kilobase-long deletion encompassing a myelin-specific enhancer of EGR2. This regulatory mutation is the first genetic abnormality associated with congenital amyelinating neuropathy in humans.

Clinical and myopathological evaluation of early- and late-onset subtypes of myofibrillar myopathy.

Myofibrillar myopathies (MFM) are a group of disorders associated with mutations in DES, CRYAB, MYOT, ZASP, FLNC, or BAG3 genes and characterized by disintegration of myofibrils and accumulation of degradation products into intracellular inclusions. We retrospectively evaluated 53 MFM patients from 35 Spanish families. Studies included neurologic exam, muscle imaging, light and electron microscopic analysis of muscle biopsy, respiratory function testing and cardiologic work-up. Search for pathogenic mutations was accomplished by sequencing of coding regions of the six genes known to cause MFM. Mutations in MYOT were the predominant cause of MFM in Spain affecting 18 of 35 families, followed by DES in 11 and ZASP in 3; in 3 families the cause of MFM remains undetermined. Comparative analysis of DES, MYOT and ZASP associated phenotypes demonstrates substantial phenotypic distinctions that should be considered in studies of disease pathogenesis, for optimization of subtype-specific treatments and management, and directing molecular analysis.

Drenagem pleural / Drainage of pleural fluids

A drenagem pleural é procedimento cirúrgico largamente utilizado na prática médica diária, que permite o restabelecimento das pressões negativas no espaço pleural. Apesar de ser considerado ato relativamente simples, poderá levar à graves complicações devido a falta de cuidados que precisam ser respeitados. Procuramos ressaltar alguns aspectos que, se não respeitados no seu conjunto, acabam determinando o insucesso dos procedimentos de drenagem de tórax.

Drainage of pleural fluids, which allows for the reestablishment of negative pressures in the pleural space, is widely employed in routine medical practice. Despite being considered a relatively simple act, it may lead to severe complications if adequate care is not taken. We will highlight some aspects which, if not well tended to, will result in unsuccessful outcome of chest drainage procedures.

Percutaneous lithotripsy in Valdivia-Galdakao decubitus position: our experience.

Percutaneous nephrolithotripsy (PNL) is actually the first therapeutic option to resolve complex renal stones. Our department initiated its experience in 1985 and treated the first 585 patients in ventral decubitus, as the original technique was described. Then, in 1998, the dorsal decubitus was adopted (Valdivia Uria), in which 695 patients were treated. Since 2006 the Valdivia Galdakao variant has been used. The Valdivia Galdakao position is an intermediate dorsal decubitus with extension of its homolateral lower limb and flexion of the contralateral. It is a practical way to place the patient for percutaneous renal surgery, avoiding hyperextensions and hyperflexions that can result in articular damage. It preserves cardiovascular and ventilatory dynamics and allows a better access to the respiratory tract. In this position, the bowel slips away from the puncture area lowering the risk of its damage. A single lumbar and genital sterile surgical field is created allowing antegrade and retrograde simultaneous endoscopic and even laparoscopic access, increasing efficiency and safety of the minimal invasive procedures. Between April 2006 and March 2008, 175 PNLs were performed in our department with the patient in Valdivia Galdakao position. The aim of this article is to describe our experience in this decubitus confirming that the Valdivia Galdakao is a safe, practical and versatile position that should be considered as first choice when a percutaneous renal surgery is indicated.

[Chemical characteristics, mechanism of action and antiviral activity of etravirine]. / Características químicas, mecanismo de acción y actividad antiviral de etravirina.

Etravirine (ETR) is a diarylpyrimidine derivative with a polycyclic molecule composed of 3 aromatic rings with single bonds between the rings (C(20)H(15)BrN(60)). The drug acts through a mechanism of noncompetitive inhibition on binding to a hydrophobic binding pocket, very close to the active center of the enzyme, provoking an allosteric transition to a conformation that distorts its structure and impedes DNA polymerization. The 3 rings with single bonds between the rings confer the molecule with great fl exibility and torsion. Because of these characteristics, etravirine can adapt to conformational changes in the binding pocket, including a large number of the conformations provoked by the resistance mutations that appear after failure to regimens that include efavirenz or nevirapine. This specific chemical structure largely explains the drug's distinguishing features in terms of its antiviral potency and high genetic barrier. ETR is a highly active molecule against HIV-1. This drug has a high genetic barrier to resistance and has demonstrated antiviral activity against a wide panel of recombinant viruses that incorporate resistance mutations to first-generation non-nucleoside analogues. Equally, ETR has demonstrated efficacy against several subtypes of the M group of HIV-1 (A, B, C, D, F and H, and recombinant forms CRF01_AE, CRF02_AG, CRF05_DF), as well as against isolates of HIV-1 group O. ETR, as the rest of non-nucleoside analogues, does not have demonstrated antiviral activity against HIV-2.

Diagnóstico microbiológico de la infección por el VIH / Microbiological diagnosis of HIV infection

En la actualidad se calcula que en España hay alrededor de 150.000 personas infectadas por el virus de la inmunodeficiencia humana (VIH). Este número, junto con el hecho de que esta enfermedad se haya convertido en una patología crónica gracias a los nuevos tratamientos antirretrovirales, condiciona una gran demanda asistencial en los laboratorios de microbiología de nuestros hospitales. Esta mayor demanda tiene lugar no sólo en el terreno del diagnóstico y tratamiento de las infecciones oportunistas, sino también en pruebas que ayudan en el diagnóstico y tratamiento terapéutico de la propia infección por el virus. Consciente de ello, la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica ha realizado una actualización de su procedimiento sobre el diagnóstico microbiológico de la infección por VIH. En dicho procedimiento se realiza una revisión de las principales novedades en el terreno del diagnóstico serológico, de la carga viral plasmática y de la detección de resistencias a los distintos retrovirales (AU)

Currently, there are around 150,000 HIV-infected patients in Spain. This number, together with the fact that this disease is now a chronic condition since the introduction of antiretroviral therapy, has generated an increasing demand on the clinical microbiology laboratories in our hospitals. This increase has occurred not only in the diagnosis and treatment of opportunistic diseases, but also in tests related to the diagnosis and therapeutic management of HIV infection. To meet this demand, the Sociedad de Enfermedades Infecciosas y Microbiología Clinica (Spanish Society of Infectious Diseases and Clinical Microbiology) has updated its standard Procedure for the microbiological diagnosis of HIV infection. The main advances related to serological diagnosis, plasma viral load, and detection of resistance to antiretroviral drugs are reviewed in this version of the Procedure (AU)

The EMBL Nucleotide Sequence Database.

The EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl), maintained at the European Bioinformatics Institute (EBI) near Cambridge, UK, is a comprehensive collection of nucleotide sequences and annotation from available public sources. The database is part of an international collaboration with DDBJ (Japan) and GenBank (USA). Data are exchanged daily between the collaborating institutes to achieve swift synchrony. Webin is the preferred tool for individual submissions of nucleotide sequences, including Third Party Annotation (TPA) and alignments. Automated procedures are provided for submissions from large-scale sequencing projects and data from the European Patent Office. New and updated data records are distributed daily and the whole EMBL Nucleotide Sequence Database is released four times a year. Access to the sequence data is provided via ftp and several WWW interfaces. With the web-based Sequence Retrieval System (SRS) it is also possible to link nucleotide data to other specialist molecular biology databases maintained at the EBI. Other tools are available for sequence similarity searching (e.g. FASTA and BLAST). Changes over the past year include the removal of the sequence length limit, the launch of the EMBLCDSs dataset, extension of the Sequence Version Archive functionality and the revision of quality rules for TPA data.

UniProt archive.

UniProt Archive (UniParc) is the most comprehensive, non-redundant protein sequence database available. Its protein sequences are retrieved from predominant, publicly accessible resources. All new and updated protein sequences are collected and loaded daily into UniParc for full coverage. To avoid redundancy, each unique sequence is stored only once with a stable protein identifier, which can be used later in UniParc to identify the same protein in all source databases. When proteins are loaded into the database, database cross-references are created to link them to the origins of the sequences. As a result, performing a sequence search against UniParc is equivalent to performing the same search against all databases cross-referenced by UniParc. UniParc contains only protein sequences and database cross-references; all other information must be retrieved from the source databases.