Gut microbiota and inflammatory mediators differentiate IgE mediated and non-IgE mediated cases of cow's milk protein at diagnosis.

OBJECTIVE: Analyze fecal and blood samples at point of diagnosis in IgE mediated cow's milk protein allergy (CMPA) and non-IgE mediated (NIM)-CMPA patients to look for potential new biomarkers. PATIENTS AND METHODS: Fourteen patients with IgE mediated CMPA and 13 with NIM-CMPA were recruited in three hospitals in the north of Spain, and were compared with 25 infants from a control group of the same age range. To characterize intestinal microbiota, 16S rDNA gene and internal transcribed spacer amplicons of bifidobacteria were sequenced with Illumina technology. Fatty acids were analyzed by gas chromatography, meanwhile intestinal inflammation markers were quantified by enzyme-linked immunosorbent assay and a multiplex system. Immunological analysis of blood was performed by flow cytometry. RESULTS: The fecal results obtained in the NIM-CMPA group stand out. Among them, a significant reduction in the abundance of Bifidobacteriaceae and Bifidobacterium sequences with respect to controls was observed. Bifidobacterial species were also different, highlighting the lower abundance of Bifidobacterium breve sequences. Fecal calprotectin levels were found to be significantly elevated in relation to IgE mediated patients. Also, a higher excretion of IL-10 and a lower excretion of IL-1ra and platelet derived growth factor-BB was found in NIM-CMPA patients. CONCLUSIONS: The differential fecal parameters found in NIM-CMPA patients could be useful in the diagnosis of NIM food allergy to CM proteins.

Microbial and immune faecal determinants in infants hospitalized with COVID-19 reflect bifidobacterial dysbiosis and immature intestinal immunity.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide, seriously endangering human health. Although SARS-CoV-2 had a lower impact on paediatric population, children with COVID-19 have been reported as suffering from gastrointestinal (GI) symptoms at a higher rate than adults. The aim of this work was to evaluate faeces as a source of potential biomarkers of severity in the paediatric population, with an emphasis on intestinal microbiota and faecal immune mediators, trying to identify possible dysbiosis and immune intestinal dysfunction associated with the risk of hospitalization. This study involved 19 patients with COVID-19 under 24 months of age hospitalized during the pandemic at 6 different hospitals in Spain, and it included a comparable age-matched healthy control group (n = 18). Patients and controls were stratified according to their age in two groups: newborns or young infants (from 0 to 3 months old) and toddlers (infants from 6 to 24 months old). To characterize microbial intestinal communities, sequencing with Illumina technology of total 16S rDNA amplicons and internal transcribed spacer (ITS) amplicons of bifidobacteria were used. Faecal calprotectin (FC) and a range of human cytokines, chemokines, and growth factors were measured in faecal samples using ELISA and a multiplex system. Significant reduction in the abundance of sequences belonging to the phylum Actinobacteria was found in those infants with COVID-19, as well as in the Bifidobacteriaceae family. A different pattern of bifidobacteria was observed in patients, mainly represented by lower percentages of Bifidobacterium breve, as compared with controls. In the group of hospitalized young infants, FC was almost absent compared to age-matched healthy controls. A lower prevalence in faecal excretion of immune factors in these infected patients was also observed. CONCLUSION:  Hospitalized infants with COVID-19 were depleted in some gut bacteria, such as bifidobacteria, in particular Bifidobacterium breve, which is crucial for the proper establishment of a functional intestinal microbiota, and important for the development of a competent immune system. Our results point to a possible immature immune system at intestine level in young infants infected by SARS-CoV2 requiring hospitalization. WHAT IS KNOWN: • Although SARS-CoV-2 had a lower impact on paediatric population, children with COVID-19 have been reported as suffering from gastrointestinal symptoms at a higher rate than adults. • Changes in microbial composition have been described in COVID-19 adult patients, although studies in children are limited. WHAT IS NEW: • The first evidence that hospitalized infants with COVID-19 during the pandemic had a depletion in bifidobacteria, particularly in Bifidobacterium breve, beneficial gut bacteria in infancy that are crucial for the proper establishment of a competent immune system. • In young infants (under 3 months of age) hospitalized with SARS-CoV2 infection, the aberrant bifidobacterial profile appears to overlap with a poor intestinal immune development as seen by calprotectin and the trend of immunological factors excreted in faeces.

A reproducible experimental survey on biomedical sentence similarity: A string-based method sets the state of the art.

This registered report introduces the largest, and for the first time, reproducible experimental survey on biomedical sentence similarity with the following aims: (1) to elucidate the state of the art of the problem; (2) to solve some reproducibility problems preventing the evaluation of most current methods; (3) to evaluate several unexplored sentence similarity methods; (4) to evaluate for the first time an unexplored benchmark, called Corpus-Transcriptional-Regulation (CTR); (5) to carry out a study on the impact of the pre-processing stages and Named Entity Recognition (NER) tools on the performance of the sentence similarity methods; and finally, (6) to bridge the lack of software and data reproducibility resources for methods and experiments in this line of research. Our reproducible experimental survey is based on a single software platform, which is provided with a detailed reproducibility protocol and dataset as supplementary material to allow the exact replication of all our experiments and results. In addition, we introduce a new aggregated string-based sentence similarity method, called LiBlock, together with eight variants of current ontology-based methods, and a new pre-trained word embedding model trained on the full-text articles in the PMC-BioC corpus. Our experiments show that our novel string-based measure establishes the new state of the art in sentence similarity analysis in the biomedical domain and significantly outperforms all the methods evaluated herein, with the only exception of one ontology-based method. Likewise, our experiments confirm that the pre-processing stages, and the choice of the NER tool for ontology-based methods, have a very significant impact on the performance of the sentence similarity methods. We also detail some drawbacks and limitations of current methods, and highlight the need to refine the current benchmarks. Finally, a notable finding is that our new string-based method significantly outperforms all state-of-the-art Machine Learning (ML) models evaluated herein.

Multilocus Data Analysis Reveal the Diversity of Cryptic Species in the Tillandsia ionantha (Bromeliaceae: Tillansiodeae) Complex.

Independent evolutionary lineages or species that lack phenotypic variation as an operative criterion for their delimitation are known as cryptic species. However, these have been delimited using other data sources and analysis. The aims of this study are: (1) to evaluate the divergence of the populations of the T. ionantha complex; and (2) to delimit the species using multilocus data, phylogenetic analysis and the coalescent model. Phylogenetic analyses, genetic diversity and population structure, and isolation by distance analysis were performed. A multispecies coalescent analysis to delimit the species was conducted. Phylogenetic analysis showed that T. ionantha is polyphyletic composed of eight evolutionary lineages. Haplotype distribution and genetic differentiation analysis detected strong population structure and high values of genetic differentiation among populations. The positive correlation between genetic differences with geographic distance indicate that the populations are evolving under the model of isolation by distance. The coalescent multispecies analysis performed with starBEAST supports the recognition of eight lineages as different species. Only three out of the eight species have morphological characters good enough to recognize them as different species, while five of them are cryptic species. Tillandsia scaposa and T. vanhyningii are corroborated as independent lineages, and T. ionantha var. stricta changed status to the species level.

Ozone treatment effectively eliminates SARS-CoV-2 from infected face masks.

The current COVID-19 pandemic is causing profound health, economic, and social problems worldwide. The global shortage of medical and personal protective equipment (PPE) in specialized centers during the outbreak demonstrated the need for efficient methods to disinfect and recycle them in times of emergency. We have previously described that high ozone concentrations destroyed viral RNA in an inactivated SARS-CoV-2 strain within a few minutes. However, the efficient ozone dosages for active SARS-CoV-2 are still unknown. The present study aimed to evaluate the systematic effects of ozone exposure on face masks from hospitalized patients infected with SARS-CoV-2. Face masks from COVID-19 patients were collected and treated with a clinical ozone generator at high ozone concentrations in small volumes for short periods. The study focused on SARS-CoV-2 gene detection (assessed by real-time quantitative polymerase chain reaction (RT-qPCR)) and on the virus inactivation by in vitro studies. We assessed the effects of different high ozone concentrations and exposure times on decontamination efficiency. We showed that high ozone concentrations (10,000, 2,000, and 4,000 ppm) and short exposure times (10, 10, and 2 minutes, respectively), inactivated both the original strain and the B.1.1.7 strain of SARS-CoV-2 from 24 contaminated face masks from COVID-19 patients. The validation results showed that the best condition for SARS-CoV-2 inactivation was a treatment of 4,000 ppm of ozone for 2 minutes. Further studies are in progress to advance the potential applications of these findings.

HESML: a real-time semantic measures library for the biomedical domain with a reproducible survey.

BACKGROUND: Ontology-based semantic similarity measures based on SNOMED-CT, MeSH, and Gene Ontology are being extensively used in many applications in biomedical text mining and genomics respectively, which has encouraged the development of semantic measures libraries based on the aforementioned ontologies. However, current state-of-the-art semantic measures libraries have some performance and scalability drawbacks derived from their ontology representations based on relational databases, or naive in-memory graph representations. Likewise, a recent reproducible survey on word similarity shows that one hybrid IC-based measure which integrates a shortest-path computation sets the state of the art in the family of ontology-based semantic measures. However, the lack of an efficient shortest-path algorithm for their real-time computation prevents both their practical use in any application and the use of any other path-based semantic similarity measure. RESULTS: To bridge the two aforementioned gaps, this work introduces for the first time an updated version of the HESML Java software library especially designed for the biomedical domain, which implements the most efficient and scalable ontology representation reported in the literature, together with a new method for the approximation of the Dijkstra's algorithm for taxonomies, called Ancestors-based Shortest-Path Length (AncSPL), which allows the real-time computation of any path-based semantic similarity measure. CONCLUSIONS: We introduce a set of reproducible benchmarks showing that HESML outperforms by several orders of magnitude the current state-of-the-art libraries in the three aforementioned biomedical ontologies, as well as the real-time performance and approximation quality of the new AncSPL shortest-path algorithm. Likewise, we show that AncSPL linearly scales regarding the dimension of the common ancestor subgraph regardless of the ontology size. Path-based measures based on the new AncSPL algorithm are up to six orders of magnitude faster than their exact implementation in large ontologies like SNOMED-CT and GO. Finally, we provide a detailed reproducibility protocol and dataset as supplementary material to allow the exact replication of all our experiments and results.

Incidence, risk factors, clinical characteristics and outcomes of deep venous thrombosis in patients with COVID-19 attending the Emergency Department: results of the UMC-19-S8.

BACKGROUND AND IMPORTANCE: A higher incidence of venous thromboembolism [both pulmonary embolism and deep vein thrombosis (DVT)] in patients with coronavirus disease 2019 (COVID-19) has been described. But little is known about the true frequency of DVT in patients who attend emergency department (ED) and are diagnosed with COVID-19. OBJECTIVE: We investigated the incidence, risk factors, clinical characteristics and outcomes of DVT in patients with COVID-19 attending the ED before hospitalization. METHODS: We retrospectively reviewed all COVID patients diagnosed with DVT in 62 Spanish EDs (20% of Spanish EDs, case group) during the first 2 months of the COVID-19 outbreak. We compared DVT-COVID-19 patients with COVID-19 without DVT patients (control group). Relative frequencies of DVT were estimated in COVID and non-COVID patients visiting the ED and annual standardized incidences were estimated for both populations. Sixty-three patient characteristics and four outcomes were compared between cases and controls. RESULTS: We identified 112 DVT in 74 814 patients with COVID-19 attending the ED [1.50‰; 95% confidence interval (CI), 1.23-1.80‰]. This relative frequency was similar than that observed in non-COVID patients [2109/1 388 879; 1.52‰; 95% CI, 1.45-1.69‰; odds ratio (OR) = 0.98 [0.82-1.19]. Standardized incidence of DVT was higher in COVID patients (98,38 versus 42,93/100,000/year; OR, 2.20; 95% CI, 2.03-2.38). In COVID patients, the clinical characteristics associated with a higher risk of presenting DVT were older age and having a history of venous thromboembolism, recent surgery/immobilization and hypertension; chest pain and desaturation at ED arrival and some analytical disturbances were also more frequently seen, d-dimer >5000 ng/mL being the strongest. After adjustment for age and sex, hospitalization, ICU admission and prolonged hospitalization were more frequent in cases than controls, whereas mortality was similar (OR, 1.37; 95% CI, 0.77-2.45). CONCLUSIONS: DVT was an unusual form of COVID presentation in COVID patients but was associated with a worse prognosis.

Protocol for a reproducible experimental survey on biomedical sentence similarity.

Measuring semantic similarity between sentences is a significant task in the fields of Natural Language Processing (NLP), Information Retrieval (IR), and biomedical text mining. For this reason, the proposal of sentence similarity methods for the biomedical domain has attracted a lot of attention in recent years. However, most sentence similarity methods and experimental results reported in the biomedical domain cannot be reproduced for multiple reasons as follows: the copying of previous results without confirmation, the lack of source code and data to replicate both methods and experiments, and the lack of a detailed definition of the experimental setup, among others. As a consequence of this reproducibility gap, the state of the problem can be neither elucidated nor new lines of research be soundly set. On the other hand, there are other significant gaps in the literature on biomedical sentence similarity as follows: (1) the evaluation of several unexplored sentence similarity methods which deserve to be studied; (2) the evaluation of an unexplored benchmark on biomedical sentence similarity, called Corpus-Transcriptional-Regulation (CTR); (3) a study on the impact of the pre-processing stage and Named Entity Recognition (NER) tools on the performance of the sentence similarity methods; and finally, (4) the lack of software and data resources for the reproducibility of methods and experiments in this line of research. Identified these open problems, this registered report introduces a detailed experimental setup, together with a categorization of the literature, to develop the largest, updated, and for the first time, reproducible experimental survey on biomedical sentence similarity. Our aforementioned experimental survey will be based on our own software replication and the evaluation of all methods being studied on the same software platform, which will be specially developed for this work, and it will become the first publicly available software library for biomedical sentence similarity. Finally, we will provide a very detailed reproducibility protocol and dataset as supplementary material to allow the exact replication of all our experiments and results.

Incidence, clinical, risk factors and outcomes of Guillain-Barré in Covid-19.

We diagnosed 11 Guillain-Barré syndrome (GBS) cases among 71,904 COVID patients attended at 61 Spanish emergency departments (EDs) during the 2-month pandemic peak. The relative frequency of GBS among ED patients was higher in COVID (0.15‰) than non-COVID (0.02‰) patients (odds ratio [OR] = 6.30, 95% confidence interval [CI] = 3.18-12.5), as was the standardized incidence (9.44 and 0.69 cases/100,000 inhabitant-years, respectively, OR = 13.5, 95% CI = 9.87-18.4). Regarding clinical characteristics, olfactory-gustatory disorders were more frequent in COVID-GBS than non-COVID-GBS (OR = 27.59, 95% CI = 1.296-587) and COVID-non-GBS (OR = 7.875, 95% CI = 1.587-39.09) patients. Although COVID-GBS patients were more frequently admitted to intensive care, mortality was not increased versus control groups. Our results suggest SARS-CoV-2 could be another viral infection causing GBS. ANN NEUROL 2021;89:598-603.

Reproducibility dataset for a large experimental survey on word embeddings and ontology-based methods for word similarity.

This data article introduces a reproducibility dataset with the aim of allowing the exact replication of all experiments, results and data tables introduced in our companion paper (Lastra-Díaz et al., 2019), which introduces the largest experimental survey on ontology-based semantic similarity methods and Word Embeddings (WE) for word similarity reported in the literature. The implementation of all our experiments, as well as the gathering of all raw data derived from them, was based on the software implementation and evaluation of all methods in HESML library (Lastra-Díaz et al., 2017), and their subsequent recording with Reprozip (Chirigati et al., 2016). Raw data is made up by a collection of data files gathering the raw word-similarity values returned by each method for each word pair evaluated in any benchmark. Raw data files were processed by running a R-language script with the aim of computing all evaluation metrics reported in (Lastra-Díaz et al., 2019), such as Pearson and Spearman correlation, harmonic score and statistical significance p-values, as well as to generate automatically all data tables shown in our companion paper. Our dataset provides all input data files, resources and complementary software tools to reproduce from scratch all our experimental data, statistical analysis and reported data. Finally, our reproducibility dataset provides a self-contained experimentation platform which allows to run new word similarity benchmarks by setting up new experiments including other unconsidered methods or word similarity benchmarks.

Food Protein-induced Enterocolitis Syndrome: Data From a Multicenter Retrospective Study in Spain.

OBJECTIVE: The aim of the study was to describe clinical, epidemiological, and management characteristics of food protein-induced enterocolitis syndrome (FPIES) cases in Spain. PATIENTS AND METHODS: Multicenter observational retrospective study. FPIES cases diagnosed in specialized units in Spain over 12 months in 2017 (January-December) according to the recently published international diagnostic criteria were included. RESULTS: One hundred twenty patients (53.3% boys) were included. The majority were acute cases (111) with mild-to-moderate severity (76.7%). Triggering foods were cow's milk (48/120), fish (38), egg (13), rice (12), and soy (1). The majority (84.2%) of the patients had FPIES to 1 food only. In addition to vomiting (100%), pallor (89.2%), and altered behavior (88.3%) were most frequently observed in acute forms. On the contrary, diarrhea (70%), abdominal distension (33.3%), and blood in stools (44.4%) were more frequently observed in chronic cases. Oral challenge was performed in 18.9% of the acute forms compared to 44.4% of the chronic forms. The most common treatment was intravenous fluids followed by ondansetron. Corticosteroids were used in 6 patients (5 with acute symptoms and 1 chronic). Seven patients were treated with antibiotics for suspicion of infection. Most cases of cow's milk FPIES were treated with extensively hydrolyzed formulas (69.8%). CONCLUSIONS: FPIES is not uncommon in our units. Unlike other published series, fish and egg are important triggers in our country. A greater knowledge and diffusion of the international consensus criteria will allow a better characterization of the cases and a standardization of their management.

Diagnostic Value of Elastography and Endobronchial Ultrasound in the Study of Hilar and Mediastinal Lymph Nodes.

BACKGROUND: The aim of this study was to explore elastography features and its ability to distinguish between benign and malignant lymph nodes by comparing the results with an anatomopathologic examination used as gold standard. METHODS: Patients were randomized in 2 groups [endobronchial ultrasound (EBUS) and EBUS-elastography]. Echographic characteristics of the lymph nodes were collected in both categories. In the EBUS-elastography group, elastographic data were also determined. RESULTS: A total of 100 lymph nodes were evaluated. Group 1 (EBUS) consisted of 57 lymph nodes. Group 2 (EBUS-elastography) included 43 lymph nodes. In group 2, lymph nodes with predominantly blue pattern were associated with a pathologic determination of malignancy, and the probability of presenting malignant infiltration with this color pattern was 86.7% (P=0.00004). Malignant lymph nodes presented less color dispersion (48.8 vs. 94.8, P=0.00013), higher ratio of blue pixels (66% vs. 32.5%, P=0.016), and higher strain ratio (7.1 vs. 2.48, P=0.005). The cut-off points to distinguish between benign and malignant lymph nodes were 4 for strain ratio, 61 for frequency histograms, and 52 for blue pixel ratio. The area under the curve of the ROC curves were 0.75, 0.83, and 0.87, respectively. Group 2 presented a lower number of nondiagnostic samples (2.3% vs. 21%, P=0.001) and a higher rate of malignant results (42% vs. 16%, P=0.005). CONCLUSION: EBUS-elastography is feasible during EBUS and may be helpful in predicting malignant lymph node infiltration. It could improve anatomopathologic sample collection and increase diagnostic efficiency.

Relative cost-effectiveness of using an extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG in managing infants with cow's milk allergy in Spain.

OBJECTIVE: To estimate the cost-effectiveness of using an extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG (eHCF + LGG; Nutramigen LGG) as a first-line management for cow's milk allergy compared with eHCF alone, and amino acid formulae in Spain, from the perspective of the Spanish National Health Service (SNS). METHODS: Decision modeling was used to estimate the probability of immunoglobulin E (IgE)-mediated and non-IgE-mediated allergic infants developing tolerance to cow's milk by 18 months. The models also estimated the SNS cost (at 2012/2013 prices) of managing infants over 18 months after starting a formula as well as the relative cost-effectiveness of each of the formulae. RESULTS: The probability of developing tolerance to cow's milk by 18 months was higher among infants with either IgE-mediated or non-IgE-mediated allergy who were fed eHCF + LGG compared with those fed one of the other formulae. The total health care cost of initially feeding infants with eHCF + LGG was less than that of feeding infants with one of the other formulae. Hence, eHCF + LGG affords the greatest value for money to the SNS for managing both IgE-mediated and non-IgE-mediated cow's milk allergy. CONCLUSION: Using eHCF + LGG instead of eHCF alone or amino acid formulae for first-line management of newly-diagnosed infants with cow's milk allergy affords a cost-effective use of publicly funded resources because it improves outcome for less cost. A randomized controlled study showing faster tolerance development in children receiving a probiotic-containing formula is required before this conclusion can be confirmed.

Aspartate aminotransferase to platelet ratio index correlates with hepatic cirrhosis but not with fibrosis in pediatric patients with intestinal failure.

BACKGROUND AND OBJECTIVES: Patients with intestinal failure (IF) require parenteral nutrition (PN) support to obtain enough nutrients to sustain growth; long-term PN use is associated with significant liver damage. The aim of this study was to analyze the use of a noninvasive test, the aspartate aminotransferase to platelet ratio index (APRI), in the diagnosis of liver disease in pediatric patients with IF. METHODS: Medical records of all Boston Children's Hospital patients who received PN and underwent a liver biopsy from January 2006 until November 2010 were reviewed. Patients with IF with a clinical diagnosis were selected. APRI was calculated as (aspartate aminotransferase [U/L]/upper normal limit) × 100/platelets (10(9) cells/L). Presence of fibrosis and cirrhosis was estimated using the METAVIR score in liver biopsies. RESULTS: Sixty-two liver biopsies from 48 patients (22 girls) were studied. Mean APRI values in the different METAVIR categories (0-1, 2-3, 4) were 1.80, 1.17, and 4.24, respectively (analysis of variance P = 0.053; Bonferroni test for cirrhosis vs fibrosis P = 0.048). APRI could significantly predict cirrhosis (odds ratio 1.2; 95% confidence interval [CI] 1.001-1.43) but not fibrosis (METAVIR 2-3, odds ratio 1.00; 95% CI 0.86-1.18). Area under the receiver operating characteristic curve for cirrhosis was 0.67 (95% CI 0.45-0.89; P = 0.13). CONCLUSIONS: APRI, a noninvasive, easy-to-obtain bedside test, significantly predicts cirrhosis but not fibrosis in pediatric patients with IFALD. Because the clinicians need a noninvasive test to differentiate among different stages of liver fibrosis rather than differentiating cirrhosis from normal, we cannot recommend the use of this test in pediatric patients with IFALD for this purpose.

Impact of early oseltamivir treatment on outcome in critically ill patients with 2009 pandemic influenza A.

OBJECTIVES: The impact of oseltamivir on mortality in critically ill patients with 2009 pandemic influenza A (2009 H1N1) is not clear. The main objective of this study was to investigate the relationship between the timing of antiviral administration and intensive care unit (ICU) outcomes. METHODS: Prospective, observational study of a cohort of ICU patients with confirmed 2009 H1N1 infection. Clinical data, treatment and outcome were compared between patients receiving early treatment (ET) with oseltamivir, initiated within 2 days, and patients administered late treatment (LT), initiated after this timepoint. Multivariate analysis and propensity score were used to determine the effect of oseltamivir on ICU mortality. RESULTS: Six hundred and fifty-seven patients were enrolled. Four hundred and four (61.5%) patients required mechanical ventilation (MV; mortality 32.6%). Among them, 385 received effective antiviral therapy and were included in the study group. All patients received oseltamivir for a median duration of 10 days (interquartile range 8-14 days). Seventy-nine (20.5%) ET patients were compared with 306 LT patients. The two groups were comparable in terms of main clinical variables. ICU length of stay (22.7 ±â€Š16.7 versus 18.4 ±â€Š14.2 days; P = 0.03), hospital length of stay (34.0 ±â€Š20.3 versus 27.2 ±â€Š18.2 days; P = 0.001) and MV days (17.4 ±â€Š15.2 versus 14.0 ±â€Š12.4; P = 0.04) were higher in the LT group. ICU mortality was also higher in LT (34.3%) than in ET (21.5%; OR = 1.9; 95% CI 1.06-3.41). A multivariate model identified ET (OR = 0.44; 95% CI 0.21-0.87) as an independent variable associated with reduced ICU mortality. These results were confirmed by propensity score analysis (OR = 0.44; 95% CI 0.22-0.90; P < 0.001). CONCLUSIONS: Our findings suggest that early oseltamivir administration was associated with favourable outcomes among critically ill ventilated patients with 2009 H1N1 virus infection.

Inhibition of EphA7 up-regulation after spinal cord injury reduces apoptosis and promotes locomotor recovery.

Functional impairment after spinal cord injury (SCI) is partially attributed to neuronal cell death, with further degeneration caused by the accompanying apoptosis of myelin-forming oligodendrocytes. The Eph receptor protein tyrosine kinase family and its cognate ligands, the ephrins, have been identified to be involved in axonal outgrowth, synapse formation, and target recognition, mainly mediated by repulsive activity. Recent reports suggest that ephrin/Eph signaling might also play a role as a physiological trigger for apoptosis during embryonic development. Here, we investigated the expression profile of EphA7, after SCI, by using a combination of quantitative real-time PCR (QRT-PCR) and immunohistochemical techniques. QRT-PCR analysis showed an increase in the expression of full-length EphA7 at 7 days postinjury (DPI). Receptor immunoreactivity was shown mostly in astrocytes of the white matter at the injury epicenter. In control animals, EphA7 expression was observed predominantly in motor neurons of the ventral gray matter, although some immunoreactivity was seen in white matter. Furthermore, blocking the expression of EphA7 after SCI using antisense oligonucleotides resulted in significant acceleration of hindlimb locomotor recovery at 1 week. This was a transient effect; by 2 weeks postinjury, treated animals were not different from controls. Antisense treatment also produced a return of nerve conduction, with shorter latencies than in control treated animals after transcranial magnetic stimulation. We identified EphA7 receptors as putative regulators of apoptosis in the acute phase after SCI. These results suggest a functional role for EphA7 receptors in the early stages of SCI pathophysiology.

Enzymatic rotating biosensor for cysteine and glutathione determination in a FIA system.

The high sensitivity that can be attained using an enzymatic system and mediated by catechols has been verified by on-line interfacing of a rotating biosensor and continuous flow/stopped-flow/continuous-flow processing. Horseradish peroxidase, HRP, [EC 1.11.1.7], immobilized on a rotating disk, in presence of hydrogen peroxide catalyzed the oxidation of catechols, whose back electrochemical reduction was detected on glassy carbon electrode surface at -150mV. Thus, when l-cysteine (Cys) or glutathione (GSH) was added to the solution, these thiol-containing compounds participate in Michael addition reactions with catechols to form the corresponding thioquinone derivatives, decreasing the peak current obtained proportionally to the increase of its concentration. Cys was used as the model thiol-containing compound for the study. The highest response for Cys was obtained around pH 7. This method could be used to determine Cys concentration in the range 0.05-90muM (r=0.998) and GSH concentration in the range 0.04-90muM (r=0.999). The determination of Cys and GSH were possible with a limit of detection of 0.7 and 0.3nM, respectively, in the processing of as many as 25 samples per hour. Current response of the HRP-rotating biosensor is not affected by the oxidized form of GSH and Cys (glutathione disulfide, GSSG, and l-cystine, respectively), by sulfur-containing and alkyl-amino compounds such as methionine and lysine, respectively. The interferences from easily oxidizable species such as ascorbic acid and uric acid are lowest.

Enzymatic rotating biosensor for ciprofloxacin determination.

The high sensitivity that can be attained using an enzymatic system and mediated by catechol has been verified by on-line interfacing of a rotating biosensor and continuous flow/stopped-flow/continuous-flow processing. Horseradish peroxidase, HRP [EC 1.11.1.7], immobilized on a rotating disk, in the presence of hydrogen peroxide, catalyzed the oxidation of catechol, whose back electrochemical reduction was detected on a glassy carbon electrode surface at -200mV. Thus, when ciprofloxacin (CF) was added to the solution, this piperazine-containing compound participate in Michael addition reactions with catechol to form the corresponding piperazine-quinone derivatives, decreasing the peak current obtained, in proportion with the increase of its concentration. The highest response for CF was obtained around pH 7. This method could be used to determine CF concentration in the range of 0.02-65muM (r=0.999). The determination of CF concentration was possible with a detection limit of 0.4nM, in the processing of as many as 25 samples per hour. Application of this analysis to different pharmaceutical samples containing CF supports the utility of the HRP-rotating biosensor.

Anticancer bisquaternary heterocyclic compounds: a ras-ional design.

A new family of symmetrical bisquaternary compounds with semirigid linkers have shown to be highly specific for Choline Kinase (ChoK) inhibition and to exert antitumoural activity in cell lines and in mice. A three-parameter regression equation has been derived which satisfactorily describes the ex vivo inhibitory potency of ChoK of the title compounds. The electronic effect of the group at position 4 of the cationic head plays a critical role although the hydrophobic contribution, especially that of the linker, favors the ChoK inhibitory activity. The antiproliferative activity (in vitro assay) is correlated with the ChoK inhibition (ex vivo assay) through the electronic effect and a squared term of the overall lipophilicity of the molecules. We also provide in vivo evidence that ChoK is a novel target for the design of antitumoural drugs. All these results suggest that ChoK plays a crucial role in the onset of carcinogenesis.