Université Nantes Angers Le Mans

BACKGROUND: Previous trials involving patients with the acute respiratory distress syndrome (ARDS) have failed to show a beneficial effect of prone positioning during mechanical ventilatory support on outcomes. We evaluated the effect of early application of prone positioning on outcomes in patients with severe ARDS. METHODS: In this multicenter, prospective, randomized, controlled trial, we randomly assigned 466 patients with severe ARDS to undergo prone-positioning sessions of at least 16 hours or to be left in the supine position. Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (FiO2) of less than 150 mm Hg, with an FiO2 of at least 0.6, a positive end-expiratory pressure of at least 5 cm of water, and a tidal volume close to 6 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died from any cause within 28 days after inclusion. RESULTS: A total of 237 patients were assigned to the prone group, and 229 patients were assigned to the supine group. The 28-day mortality was 16.0% in the prone group and 32.8% in the supine group (P<0.001). The hazard ratio for death with prone positioning was 0.39 (95% confidence interval [CI], 0.25 to 0.63). Unadjusted 90-day mortality was 23.6% in the prone group versus 41.0% in the supine group (P<0.001), with a hazard ratio of 0.44 (95% CI, 0.29 to 0.67). The incidence of complications did not differ significantly between the groups, except for the incidence of cardiac arrests, which was higher in the supine group. CONCLUSIONS: In patients with severe ARDS, early application of prolonged prone-positioning sessions significantly decreased 28-day and 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique National 2006 and 2010 of the French Ministry of Health; PROSEVA ClinicalTrials.gov number, NCT00527813.).

UNLABELLED: Several animal studies have emphasized the role of gut microbiota in nonalcoholic fatty liver disease (NAFLD). However, data about gut dysbiosis in human NAFLD remain scarce in the literature, especially studies including the whole spectrum of NAFLD lesions. We aimed to evaluate the association between gut dysbiosis and severe NAFLD lesions, that is, nonalcoholic steatohepatitis (NASH) and fibrosis, in a well-characterized population of adult NAFLD. Fifty-seven patients with biopsy-proven NAFLD were enrolled. Taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples. Thirty patients had F0/F1 fibrosis stage at liver biopsy (10 with NASH), and 27 patients had significant F≥2 fibrosis (25 with NASH). Bacteroides abundance was significantly increased in NASH and F≥2 patients, whereas Prevotella abundance was decreased. Ruminococcus abundance was significantly higher in F≥2 patients. By multivariate analysis, Bacteroides abundance was independently associated with NASH and Ruminococcus with F≥2 fibrosis. Stratification according to the abundance of these two bacteria generated three patient subgroups with increasing severity of NAFLD lesions. Based on imputed metagenomic profiles, Kyoto Encyclopedia of Genes and Genomes pathways significantly related to NASH and fibrosis F≥2 were mostly related to carbohydrate, lipid, and amino acid metabolism. CONCLUSION: NAFLD severity associates with gut dysbiosis and a shift in metabolic function of the gut microbiota. We identified Bacteroides as independently associated with NASH and Ruminococcus with significant fibrosis. Thus, gut microbiota analysis adds information to classical predictors of NAFLD severity and suggests novel metabolic targets for pre-/probiotics therapies.

MAXENT is now a common species distribution modeling (SDM) tool used by conservation practitioners for predicting the distribution of a species from a set of records and environmental predictors. However, datasets of species occurrence used to train the model are often biased in the geographical space because of unequal sampling effort across the study area. This bias may be a source of strong inaccuracy in the resulting model and could lead to incorrect predictions. Although a number of sampling bias correction methods have been proposed, there is no consensual guideline to account for it. We compared here the performance of five methods of bias correction on three datasets of species occurrence: one "virtual" derived from a land cover map, and two actual datasets for a turtle (Chrysemys picta) and a salamander (Plethodon cylindraceus). We subjected these datasets to four types of sampling biases corresponding to potential types of empirical biases. We applied five correction methods to the biased samples and compared the outputs of distribution models to unbiased datasets to assess the overall correction performance of each method. The results revealed that the ability of methods to correct the initial sampling bias varied greatly depending on bias type, bias intensity and species. However, the simple systematic sampling of records consistently ranked among the best performing across the range of conditions tested, whereas other methods performed more poorly in most cases. The strong effect of initial conditions on correction performance highlights the need for further research to develop a step-by-step guideline to account for sampling bias. However, this method seems to be the most efficient in correcting sampling bias and should be advised in most cases.

Background & AimsElafibranor is an agonist of the peroxisome proliferator−activated receptor-α and peroxisome proliferator−activated receptor-δ. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. We assessed the safety and efficacy of elafibranor in an international, randomized, double-blind placebo-controlled trial of patients with nonalcoholic steatohepatitis (NASH).MethodsPatients with NASH without cirrhosis were randomly assigned to groups given elafibranor 80 mg (n = 93), elafibranor 120 mg (n = 91), or placebo (n = 92) each day for 52 weeks at sites in Europe and the United States. Clinical and laboratory evaluations were performed every 2 months during this 1-year period. Liver biopsies were then collected and patients were assessed 3 months later. The primary outcome was resolution of NASH without fibrosis worsening, using protocol-defined and modified definitions. Data from the groups given the different doses of elafibranor were compared with those from the placebo group using step-down logistic regression, adjusting for baseline nonalcoholic fatty liver disease activity score.ResultsIn intention-to-treat analysis, there was no significant difference between the elafibranor and placebo groups in the protocol-defined primary outcome. However, NASH resolved without fibrosis worsening in a higher proportion of patients in the 120-mg elafibranor group vs the placebo group (19% vs 12%; odds ratio = 2.31; 95% confidence interval: 1.02−5.24; P = .045), based on a post-hoc analysis for the modified definition. In post-hoc analyses of patients with nonalcoholic fatty liver disease activity score ≥4 (n = 234), elafibranor 120 mg resolved NASH in larger proportions of patients than placebo based on the protocol definition (20% vs 11%; odds ratio = 3.16; 95% confidence interval: 1.22−8.13; P = .018) and the modified definitions (19% vs 9%; odds ratio = 3.52; 95% confidence interval: 1.32–9.40; P = .013). Patients with NASH resolution after receiving elafibranor 120 mg had reduced liver fibrosis stages compared with those without NASH resolution (mean reduction of 0.65 ± 0.61 in responders for the primary outcome vs an increase of 0.10 ± 0.98 in nonresponders; P < .001). Liver enzymes, lipids, glucose profiles, and markers of systemic inflammation were significantly reduced in the elafibranor 120-mg group vs the placebo group. Elafibranor was well tolerated and did not cause weight gain or cardiac events, but did produce a mild, reversible increase in serum creatinine (effect size vs placebo: increase of 4.31 ± 1.19 μmol/L; P < .001).ConclusionsA post-hoc analysis of data from trial of patients with NASH showed that elafibranor (120 mg/d for 1 year) resolved NASH without fibrosis worsening, based on a modified definition, in the intention-to-treat analysis and in patients with moderate or severe NASH. However, the predefined end point was not met in the intention to treat population. Elafibranor was well tolerated and improved patients’ cardiometabolic risk profile. ClinicalTrials.gov number: NCT01694849. Elafibranor is an agonist of the peroxisome proliferator−activated receptor-α and peroxisome proliferator−activated receptor-δ. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. We assessed the safety and efficacy of elafibranor in an international, randomized, double-blind placebo-controlled trial of patients with nonalcoholic steatohepatitis (NASH). Patients with NASH without cirrhosis were randomly assigned to groups given elafibranor 80 mg (n = 93), elafibranor 120 mg (n = 91), or placebo (n = 92) each day for 52 weeks at sites in Europe and the United States. Clinical and laboratory evaluations were performed every 2 months during this 1-year period. Liver biopsies were then collected and patients were assessed 3 months later. The primary outcome was resolution of NASH without fibrosis worsening, using protocol-defined and modified definitions. Data from the groups given the different doses of elafibranor were compared with those from the placebo group using step-down logistic regression, adjusting for baseline nonalcoholic fatty liver disease activity score. In intention-to-treat analysis, there was no significant difference between the elafibranor and placebo groups in the protocol-defined primary outcome. However, NASH resolved without fibrosis worsening in a higher proportion of patients in the 120-mg elafibranor group vs the placebo group (19% vs 12%; odds ratio = 2.31; 95% confidence interval: 1.02−5.24; P = .045), based on a post-hoc analysis for the modified definition. In post-hoc analyses of patients with nonalcoholic fatty liver disease activity score ≥4 (n = 234), elafibranor 120 mg resolved NASH in larger proportions of patients than placebo based on the protocol definition (20% vs 11%; odds ratio = 3.16; 95% confidence interval: 1.22−8.13; P = .018) and the modified definitions (19% vs 9%; odds ratio = 3.52; 95% confidence interval: 1.32–9.40; P = .013). Patients with NASH resolution after receiving elafibranor 120 mg had reduced liver fibrosis stages compared with those without NASH resolution (mean reduction of 0.65 ± 0.61 in responders for the primary outcome vs an increase of 0.10 ± 0.98 in nonresponders; P < .001). Liver enzymes, lipids, glucose profiles, and markers of systemic inflammation were significantly reduced in the elafibranor 120-mg group vs the placebo group. Elafibranor was well tolerated and did not cause weight gain or cardiac events, but did produce a mild, reversible increase in serum creatinine (effect size vs placebo: increase of 4.31 ± 1.19 μmol/L; P < .001). A post-hoc analysis of data from trial of patients with NASH showed that elafibranor (120 mg/d for 1 year) resolved NASH without fibrosis worsening, based on a modified definition, in the intention-to-treat analysis and in patients with moderate or severe NASH. However, the predefined end point was not met in the intention to treat population. Elafibranor was well tolerated and improved patients’ cardiometabolic risk profile. ClinicalTrials.gov number: NCT01694849.

Biofilms are widespread in nature and constitute an important strategy implemented by microorganisms to survive in sometimes harsh environmental conditions. They can be beneficial or have a negative impact particularly when formed in industrial settings or on medical devices. As such, research into the formation and elimination of biofilms is important for many disciplines. Several new methodologies have been recently developed for, or adapted to, biofilm studies that have contributed to deeper knowledge on biofilm physiology, structure and composition. In this review, traditional and cutting-edge methods to study biofilm biomass, viability, structure, composition and physiology are addressed. Moreover, as there is a lack of consensus among the diversity of techniques used to grow and study biofilms. This review intends to remedy this, by giving a critical perspective, highlighting the advantages and limitations of several methods. Accordingly, this review aims at helping scientists in finding the most appropriate and up-to-date methods to study their biofilms.

IMPORTANCE: D-dimer measurement is an important step in the diagnostic strategy of clinically suspected acute pulmonary embolism (PE), but its clinical usefulness is limited in elderly patients. OBJECTIVE: To prospectively validate whether an age-adjusted D-dimer cutoff, defined as age × 10 in patients 50 years or older, is associated with an increased diagnostic yield of D-dimer in elderly patients with suspected PE. DESIGN, SETTINGS, AND PATIENTS: A multicenter, multinational, prospective management outcome study in 19 centers in Belgium, France, the Netherlands, and Switzerland between January 1, 2010, and February 28, 2013. INTERVENTIONS: All consecutive outpatients who presented to the emergency department with clinically suspected PE were assessed by a sequential diagnostic strategy based on the clinical probability assessed using either the simplified, revised Geneva score or the 2-level Wells score for PE; highly sensitive D-dimer measurement; and computed tomography pulmonary angiography (CTPA). Patients with a D-dimer value between the conventional cutoff of 500 µg/L and their age-adjusted cutoff did not undergo CTPA and were left untreated and formally followed-up for a 3-month period. MAIN OUTCOMES AND MEASURES: The primary outcome was the failure rate of the diagnostic strategy, defined as adjudicated thromboembolic events during the 3-month follow-up period among patients not treated with anticoagulants on the basis of a negative age-adjusted D-dimer cutoff result. RESULTS: Of the 3346 patients with suspected PE included, the prevalence of PE was 19%. Among the 2898 patients with a nonhigh or an unlikely clinical probability, 817 patients (28.2%) had a D-dimer level lower than 500 µg/L (95% CI, 26.6%-29.9%) and 337 patients (11.6%) had a D-dimer between 500 µg/L and their age-adjusted cutoff (95% CI, 10.5%-12.9%). The 3-month failure rate in patients with a D-dimer level higher than 500 µg/L but below the age-adjusted cutoff was 1 of 331 patients (0.3% [95% CI, 0.1%-1.7%]). Among the 766 patients 75 years or older, of whom 673 had a nonhigh clinical probability, using the age-adjusted cutoff instead of the 500 µg/L cutoff increased the proportion of patients in whom PE could be excluded on the basis of D-dimer from 43 of 673 patients (6.4% [95% CI, 4.8%-8.5%) to 200 of 673 patients (29.7% [95% CI, 26.4%-33.3%), without any additional false-negative findings. CONCLUSIONS AND RELEVANCE: Compared with a fixed D-dimer cutoff of 500 µg/L, the combination of pretest clinical probability assessment with age-adjusted D-dimer cutoff was associated with a larger number of patients in whom PE could be considered ruled out with a low likelihood of subsequent clinical venous thromboembolism. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01134068.

Despite current recommendations on the management of pre-operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the peri-operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. We urge anaesthetists and peri-operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources.

Butyrate is a natural substance present in biological liquids and tissues. The present paper aims to give an update on the biological role of butyrate in mammals, when it is naturally produced by the gastrointestinal microbiota or orally ingested as a feed additive. Recent data concerning butyrate production delivery as well as absorption by the colonocytes are reported. Butyrate cannot be detected in the peripheral blood, which indicates fast metabolism in the gut wall and/or in the liver. In physiological conditions, the increase in performance in animals could be explained by the increased nutrient digestibility, the stimulation of the digestive enzyme secretions, a modification of intestinal luminal microbiota and an improvement of the epithelial integrity and defence systems. In the digestive tract, butyrate can act directly (upper gastrointestinal tract or hindgut) or indirectly (small intestine) on tissue development and repair. Direct trophic effects have been demonstrated mainly by cell proliferation studies, indicating a faster renewal of necrotic areas. Indirect actions of butyrate are believed to involve the hormono-neuro-immuno system. Butyrate has also been implicated in down-regulation of bacteria virulence, both by direct effects on virulence gene expression and by acting on cell proliferation of the host cells. In animal production, butyrate is a helpful feed additive, especially when ingested soon after birth, as it enhances performance and controls gut health disorders caused by bacterial pathogens. Such effects could be considered for new applications in human nutrition.

SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice.

Superparamagnetic ferrite nanoparticles (MFe2O4, where M = Fe, Co, Mn) were synthesized through a novel one-step aqueous coprecipitation method based on the use of a new type of alkaline agent: the alkanolamines isopropanolamine and diisopropanolamine. The role played by the bases on the particles’ size, chemical composition, and magnetic properties was investigated and compared directly with the effect of the traditional inorganic base NaOH. The novel MFe2O4 nanomaterials exhibited high colloidal stability, particle sizes in the range of 4–12 nm, and superparamagnetic properties. More remarkably, they presented smaller particle sizes (up to 6 times) and enhanced saturation magnetization (up to 1.3 times) relative to those prepared with NaOH. Furthermore, the nanomaterials exhibited improved magnetic properties when compared with nanoferrites of similar size synthesized by coprecipitation with other bases or by other methods reported in the literature. The alkanolamines were responsible for these achievements by acting both as alkaline agents and as complexing agents that controlled the particle size during the synthesis process and improved the spin rearrangement at the surface (thinner magnetic “dead” layers). These results open new horizons for the design of water-dispersible MFe2O4 nanoparticles with tuned properties through a versatile and easily scalable coprecipitation route.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) has become a major public health issue. The goal of this study was to assess the clinical use of liver stiffness measurement (LSM) evaluated by supersonic shear imaging (SSI), FibroScan, and acoustic radiation force impulse (ARFI) in a cohort of NAFLD patients who underwent liver biopsy. A total of 291 NAFLD patients were prospectively enrolled from November 2011 to February 2015 at 2 French university hospitals. LSM was assessed by SSI, FibroScan (M probe), and ARFI within two weeks prior to liver biopsy. Calculations of the area under the receiver operating curve (AUROC) were performed and compared for the staging of liver fibrosis. AUROC for SSI, FibroScan, and ARFI were 0.86, 0.82, and 0.77 for diagnoses of ≥F2; 0.89, 0.86, and 0.84 for ≥F3; and 0.88, 0.87, and 0.84 for F4, respectively. SSI had a higher accuracy than ARFI for diagnoses of significant fibrosis (≥F2) (P = 0.004). Clinical factors related to obesity such as body mass index ≥ 30 kg/m(2) , waist circumference ≥102 cm or increased parietal wall thickness were associated with LSM failures when using SSI or FibroScan and with unreliable results when using ARFI. In univariate analysis, FibroScan values were slightly correlated with NAFLD activity score and steatosis (R = 0.28 and 0.22, respectively), whereas SSI and ARFI were not; however, these components of NAFLD did not affect LSM results in multivariate analysis. The cutoff values for SSI and FibroScan for staging fibrosis with a sensitivity ≥90% were very close: 6.3/6.2 kPa for ≥F2, 8.3/8.2 kPa for ≥F3, and 10.5/9.5 kPa for F4. CONCLUSION: Although obesity is associated with an increase in LSM failure, the studied techniques and especially SSI provide high value for the diagnosis of liver fibrosis in NAFLD patients. (Hepatology 2016;63:1817-1827).

RATIONALE: Many patients with severe acute respiratory distress syndrome (ARDS) caused by influenza A(H1N1) infection receive extracorporeal membrane oxygenation (ECMO) as a rescue therapy. OBJECTIVES: To analyze factors associated with death in ECMO-treated patients and the influence of ECMO on intensive care unit (ICU) mortality. METHODS: Data from patients admitted for H1N1-associated ARDS to French ICUs were prospectively collected from 2009 to 2011 through the national REVA registry. We analyzed factors associated with in-ICU death in ECMO recipients, and the potential benefit of ECMO using a propensity score-matched (1:1) cohort analysis. MEASUREMENTS AND MAIN RESULTS: A total of 123 patients received ECMO. By multivariate analysis, increasing values of age, lactate, and plateau pressure under ECMO were associated with death. Of 103 patients receiving ECMO during the first week of mechanical ventilation, 52 could be matched to non-ECMO patients of comparable severity, using a one-to-one matching and using control subjects only once. Mortality did not differ between the two matched cohorts (odds ratio, 1.48; 95% confidence interval, 0.68-3.23; P = 0.32). Interestingly, the 51 ECMO patients who could not be matched were younger, had lower Pa(o(2))/Fi(o(2)) ratio, had higher plateau pressure, but also had a lower ICU mortality rate than the 52 matched ECMO patients (22% vs. 50%; P < 0.01). CONCLUSIONS: Under ECMO, an ultraprotective ventilation strategy minimizing plateau pressure may be required to improve outcome. When patients with severe influenza A(H1N1)-related ARDS treated with ECMO were compared with conventionally treated patients, no difference in mortality rates existed. The unmatched, severely hypoxemic, and younger ECMO-treated patients had, however, a lower mortality.

This paper proposes a new algorithm for automatic crack detection from 2D pavement images. It strongly relies on the localization of minimal paths within each image, a path being a series of neighboring pixels and its score being the sum of their intensities. The originality of the approach stems from the proposed way to select a set of minimal paths and the two postprocessing steps introduced to improve the quality of the detection. Such an approach is a natural way to take account of both the photometric and geometric characteristics of pavement images. An intensive validation is performed on both synthetic and real images (from five different acquisition systems), with comparisons to five existing methods. The proposed algorithm provides very robust and precise results in a wide range of situations, in a fully unsupervised manner, which is beyond the current state of the art.

IMPORTANCE: Although retrievable inferior vena cava filters are frequently used in addition to anticoagulation in patients with acute venous thromboembolism, their benefit-risk ratio is unclear. OBJECTIVE: To evaluate the efficacy and safety of retrievable vena cava filters plus anticoagulation vs anticoagulation alone for preventing pulmonary embolism recurrence in patients presenting with acute pulmonary embolism and a high risk of recurrence. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label, blinded end point trial (PREPIC2) with 6-month follow-up conducted from August 2006 to January 2013. Hospitalized patients with acute, symptomatic pulmonary embolism associated with lower-limb vein thrombosis and at least 1 criterion for severity were assigned to retrievable inferior vena cava filter implantation plus anticoagulation (filter group; n = 200) or anticoagulation alone with no filter implantation (control group; n = 199). Initial hospitalization with ambulatory follow-up occurred in 17 French centers. INTERVENTIONS: Full-dose anticoagulation for at least 6 months in all patients. Insertion of a retrievable inferior vena cava filter in patients randomized to the filter group. Filter retrieval was planned at 3 months from placement. MAIN OUTCOMES AND MEASURES: Primary efficacy outcome was symptomatic recurrent pulmonary embolism at 3 months. Secondary outcomes were recurrent pulmonary embolism at 6 months, symptomatic deep vein thrombosis, major bleeding, death at 3 and 6 months, and filter complications. RESULTS: In the filter group, the filter was successfully inserted in 193 patients and was retrieved as planned in 153 of the 164 patients in whom retrieval was attempted. By 3 months, recurrent pulmonary embolism had occurred in 6 patients (3.0%; all fatal) in the filter group and in 3 patients (1.5%; 2 fatal) in the control group (relative risk with filter, 2.00 [95% CI, 0.51-7.89]; P = .50). Results were similar at 6 months. No difference was observed between the 2 groups regarding the other outcomes. Filter thrombosis occurred in 3 patients. CONCLUSIONS AND RELEVANCE: Among hospitalized patients with severe acute pulmonary embolism, the use of a retrievable inferior vena cava filter plus anticoagulation compared with anticoagulation alone did not reduce the risk of symptomatic recurrent pulmonary embolism at 3 months. These findings do not support the use of this type of filter in patients who can be treated with anticoagulation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00457158.

Purpose This paper provides a structured literature review of sustainability in purchasing and supply management, moving beyond the traditional environmental and social sustainability. The paper reviews the concept of sustainability at three levels of inter‐organizational analysis – i.e. dyad, supply chain and network. The paper distils the nature and scope of existing research and synthesizes measures used to research sustainability across organizational boundaries. Design/methodology/approach This literature review systematically analyzes existing literature. In particular, the review focuses on definitions and measures of sustainable purchasing and supply management to obtain an accurate view of current research. Findings This paper uncovers two distinct trends in the type of research carried out. First, internal or dyadic issues are in focus and second, a tendency to deal with environmental, as opposed to social, sustainability. Despite the need to look beyond the dyad given the risks associated with the extended network, few studies do so in any of the sustainability dimensions. Research limitations/implications This review is limited by the method employed focusing on definitions and measures. Although the review considers supply chain and network research, it does so purely from a purchasing perspective, thus excluding issues such as logistics and transport. Practical implications The paper identifies areas open to future research and provides practical insights into how sustainable purchasing and supply are measured. It also synthesizes existing measures of sustainability at different levels and organizes these into a taxonomy. Originality/value The paper examines studies across multiple levels of analysis and integrates multiple fields of knowledge to show how research on sustainability in purchasing and supply is structured.

Brugada syndrome is a genetic disease associated with sudden cardiac death that is characterized by ventricular fibrillation and right precordial ST segment elevation on ECG. Loss-of-function mutations in SCN5A, which encodes the predominant cardiac sodium channel alpha subunit NaV1.5, can cause Brugada syndrome and cardiac conduction disease. However, SCN5A mutations are not detected in the majority of patients with these syndromes, suggesting that other genes can cause or modify presentation of these disorders. Here, we investigated SCN1B, which encodes the function-modifying sodium channel beta1 subunit, in 282 probands with Brugada syndrome and in 44 patients with conduction disease, none of whom had SCN5A mutations. We identified 3 mutations segregating with arrhythmia in 3 kindreds. Two of these mutations were located in a newly described alternately processed transcript, beta1B. Both the canonical and alternately processed transcripts were expressed in the human heart and were expressed to a greater degree in Purkinje fibers than in heart muscle, consistent with the clinical presentation of conduction disease. Sodium current was lower when NaV1.5 was coexpressed with mutant beta1 or beta1B subunits than when it was coexpressed with WT subunits. These findings implicate SCN1B as a disease gene for human arrhythmia susceptibility.

With the constant increase in poultry meat consumption worldwide and the large variety of poultry meat products and consumer demand, ensuring the microbial safety of poultry carcasses and cuts is essential. In the present review, we address the bacterial contamination of poultry meat from the slaughtering steps to the use-by-date of the products. The different contamination sources are identified. The contaminants occurring in poultry meat cuts and their behavior toward sanitizing treatments or various storage conditions are discussed. A list of the main pathogenic bacteria of concern for the consumer and those responsible for spoilage and waste of poultry meat is established.

BACKGROUND: Drug patch tests (PTs) can reproduce delayed hypersensitivity to drugs and entail a moderate re-exposure of patients to offending drugs. OBJECTIVES: To determine the value of PTs for identifying the responsible drug in severe cutaneous adverse drug reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: In a multicentre study, PTs were conducted on patients referred for DRESS, AGEP or SJS/TEN within 1 year of their SCAR. All drugs administered in the 2 months prior to and the week following the onset of the SCAR were tested. RESULTS: Among the 134 patients included (48 male, 86 female; mean age 51·7 years), positive drug PTs were obtained for 24 different drugs. These included positive tests for 64% (46/72) of patients with DRESS, 58% (26/45) of those with AGEP and 24% (4/17) of those with SJS/TEN, with only one relapse of AGEP. The value of PTs depended on the type of drug and the type of SCAR (e.g. carbamazepine was positive in 11/13 DRESS cases but none of the five SJS/TEN cases). PTs were frequently positive for beta lactams (22 cases), pristinamycin (11 cases) and in DRESS with pump proton inhibitors (five cases), but were usually negative for allopurinol and salazopyrin. Of 18 patients with DRESS, eight had virus reactivation and positive PTs. In DRESS, multiple drug reactivity was frequent (18% of cases), with patients remaining sensitized many years later. CONCLUSIONS: PTs are useful and safe for identifying agents inducing SCAR.

BACKGROUND Critically ill neonates are at high risk for adverse neurologic sequelae, but the bedside evaluation of a neonate's neurologic status, especially cortical functioning, is extremely limited. In such circumstances, continuous video EEG provides particularly useful information about brain function and can identify electroencephalographic seizures without clinical correlate (Clancy et al., 1988; Murray et al., 2008). For these reasons, continuous video EEG monitoring is a useful tool in the intensive care nursery. The American Clinical Neurophysiology Society has recently produced guidelines regarding methods and indications for continuous EEG monitoring in neonates (Shellhaas et al., 2011). A challenge in EEG monitoring of neonates is to understand the clinical significance of various EEG patterns. In the adult population in intensive care unit, there has been extensive debate, for example, regarding the importance of fluctuating rhythmic patterns (Hirsch et al., 2004; Oddo et al., 2009; Orta et al., 2009; Vespa et al., 1999). The American Clinical Neurophysiology Society Critical Care Monitoring Committee has generated standardized terminology of rhythmic EEG patterns in the critically ill to facilitate multicenter collaborations to determine whether these patterns have clinical significance (Hirsch et al., 2005). Neonates have distinctive EEG patterns that necessitate separate terminology. This document is the consensus of experts to establish standardized neonatal EEG nomenclature aimed at improving consistency and facilitating collaborative research. Where evidence exists to support a particular definition, it is noted. For terms with historically variable definitions, alternative nomenclature is referenced but a single definition is proposed. We anticipate that future revisions will incorporate feedback and emerging research building on this initial effort. Many of the studies on which these criteria are based used routine-length EEG recordings, and in this limited context, values such as acceptable duration of interburst intervals have been offered. However, greater variability may be expected in recordings of longer duration. It is hoped that this document provides groundwork for collaboration to determine the clinical significance of various EEG patterns in continuous monitoring of the critically ill neonate. DETAILS TO BE REPORTED Characterization of a 24-hour period of continuous video EEG recording should include the following (Table 1). Documentation of the patient’s postmenstrual age (PMA = gestational age, measured from the time of the last menstrual period + chronological age) at the time of recording (Engle, 2004) (We use the term PMA in accordance with the American Academy of Pediatrics policy statement on age terminology in the perinatal period. However, we recognize that historically, many seminal investigations of EEG ontogeny calculated gestational age from the time of conception rather than the last menstrual period. This has been traditionally termed conceptional age (CA). The LMP occurs approximately 2 weeks before conception.). a) Term = 37 up to 44 weeks of PMA b) Preterm = less than 37 weeks of PMA c) Post term = 44 to 48 weeks of PMA Documentation of neuroactive medications at the time of recording. This includes sedatives, hypnotics, anxiolytics, general anesthesia, and antiepileptic drugs. An ideal report would also document when these medications are administered during the recording. Documentation of the depth and duration of hypothermia during the recording, and whether it is spontaneous or induced. An ideal report would also document the clinical changes that have the potential to impact cerebral function. These would include sudden hemodynamic instability, rapid changes in respiratory function, or cardiorespiratory failure. Documentation of the number of hours of recording that cannot be interpreted as a result of technical problems. Detailed characterization of the background EEG features during the first hour of recording. Presence or absence of state changes must be included. Characterization of 1 hour of background recording within each 24-hour period of EEG monitoring. Characterization of additional epochs of background when there are relevant changes. Relevant changes include evidence for not only the increasing encephalopathy but also the new development of episodic state changes. Documentation of seizure onset, seizure burden, and seizure resolution. When present, specific note should also be made of the beginning and end of status epilepticus. TABLE 1: Details to Include in Daily EEG ReportThe normal neonatal EEG evolves as the brain matures, reflecting both antenatal and postnatal experiences. All else being equal, two healthy infants with the same PMA should have very similar appearing EEG recordings. There should be no visible differences between an EEG recorded from a 5-week chronological age infant born at 35 weeks of estimated gestational age (PMA = 40 weeks) compared with a 1-week chronological age baby born at 39 weeks EGA (PMA is also 40 weeks). However, in contrast to the older child or adult, the age difference of a few weeks can cause visible changes in normal EEG features. The following text proposes nomenclature to describe normal and abnormal features of the EEG in the preterm and term infants. Where relevant, it refers to the specific PMA at which various features are seen. We focus specifically on normal state changes, background features, graphoelements (or named neonatal EEG features), seizures, and rhythmic or periodic patterns. BEHAVIORAL STATE Standardized descriptions of the behavioral state and sleep–wake cycling are particularly useful in considering whether a neonatal record is normal or abnormal. Features of a full-term neonatal EEG and polysomnographic recording emerge over time in the premature infant. A behavioral state is said to be present when features of that state are present for 1 minute or longer (Table 2).TABLE 2: Behavioral StateAwake Term A healthy term neonate is awake when the eyes are open, and the EEG background has continuous, low to medium voltage [25–50 µV peak-to-peak (pp)] mixed frequency activity with a predominance of theta and delta and overriding beta activity (Fig. 1) (all voltages included in this article refer to pp values). This is traditionally called activité moyenne, roughly meaning “average or medium” EEG background activity. During wakefulness, term infants have irregular respirations, and there are spontaneous movements of the limbs and body.FIG. 1: Examples of EEG background classification by voltage.Preterm A healthy preterm infant is considered awake when the eyes are open. This remains its premier clinical characteristic until 32 to 34 weeks of PMA, when other polysomnographic signs (irregular respiratory patterns, phasic or tonic chin EMG activity, and the presence of small and large body movements) are also reliably concordant with wakefulness. Brief portions of the awake EEG are continuous at 28 weeks of PMA. The awake background is even more continuous by 32 weeks and persistently continuous by 34 weeks and thereafter. Sleep Sleep in the neonate is classified as active, quiet, transitional, and indeterminate. Each has distinctive EEG and polysomnographic features. Active Sleep Term. The healthy term neonate in active sleep has the eyes closed, intermittent periods of rapid eye movements, and irregular respirations with small and large body movements. The EEG background shows activité moyenne, indistinguishable from that of normal wakefulness. Preterm. Tracé discontinu describes the normal discontinuous tracing encountered in healthy preterm babies (Figs. 1, 2A). This EEG pattern is characterized by bursts of high voltage (50–300 µV pp) activity that are regularly interrupted by low voltage interburst periods (<25 µV pp) (Clancy and Wusthoff, 2011). The duration of the low voltage interburst periods is dependent on PMA, being longest in the youngest PMA infants. The bursts of EEG activity have expected and recognizable constituents such as monorhythmic occipital delta activity and other patterns that are described below. Tracé discontinu predominates before 28 weeks of PMA. Brief and inconsistent periods of continuous EEG activity occur first in waking state and active sleep along with rapid eye movements at 25 weeks of PMA (Scher et al., 2005a). Movements (face and body) in active sleep tend to be segmental myoclonus or generalized myoclonic and tonic posturing. By 28 to 31 weeks of PMA, there are some periods with complete features of active sleep (eyes closed, rapid eye movements, irregular respirations, body movements, and continuous EEG). After 34 weeks, active sleep consistently has continuous EEG activity.FIG. 2: Examples illustrating the contrasts between tracé discontinu, tracé alternant, excessive discontinuity, and burst suppression. EEG tracings courtesy of Clancy and Wusthoff, 2011. A, In tracé discontinu, the bursts are separated by very low voltage, suppressed IBIs. There are no artifacts from EMG activity or movement, and the respiratory pattern is quite regular. B, In this example of tracé alternant, however, there is an alternating pattern of high and low voltages but no periods that are consistently suppressed. There are no artifacts from EMG activity or movement, and the respiratory pattern is quite regular. C, This excessively discontinuous record from a term infant with an acute encephalopathy showing prolonged IBIs, although with some normal features present during bursts, such as the conspicuous encoche frontale seen near its onset (arrow). D, Burst suppression, in contrast, contains prolonged, extremely suppressed IBIs and bursts composed exclusively of abnormal electrical activity.Quiet Sleep Term. In the healthy term neonate, quiet sleep is clinically characterized by eye closure, absence of rapid eye movements, and scant body movements, except for occasional sucking activity or generalized myoclonic “startles.” The quiet sleep EEG background near term, tracé alternant, evolves from the less mature tracé discontinu in the preterm (Figs. 1, 2B). It shows the “alternating tracing” in which higher voltage bursts (50–150 µV pp), comprised predominantly of delta activity and lasting roughly 4 to 10 seconds, alternate with briefer, lower voltage (25–50 µV pp) (Lamblin et al., 1999) interburst periods composed mostly of mixed theta and delta activity. These interburst periods of tracé alternant, taken in isolation, greatly resemble the characteristics of activité moyenne with its low to medium voltage, mixed frequency activity. Tracé alternant gradually disappears with age and is minimal by 42 weeks and vanishes by 46 weeks. As tracé alternant fades, it is replaced in quiet sleep by the more mature, fully continuous quiet sleep background composed of nonstop, high-voltage (50–150 µV pp) delta and theta activity. Sleep spindles around 10 to 12 Hz first appear within this continuous slow wave sleep pattern by 46 weeks of PMA. Preterm. In the very preterm neonate, most of the EEG background is discontinuous in all behavioral states. With advancing PMA, wakefulness and active sleep are distinguished from quiet sleep by greater periods of continuity. Tracé discontinu is the defining feature of quiet sleep first emerging approximately 28 weeks of PMA. By 34 to 36 weeks, tracé discontinu is seen only in quiet sleep. The amount of time with a tracé discontinu pattern decreases with increasing PMA so that a term infant has rare, if any, periods of tracé discontinu in quiet sleep (Hahn et al., 1989). By 37 to 40 weeks, tracé alternant fully replaces tracé discontinu, as described above. Transitional Sleep In between states of waking, active sleep, and quiet sleep, there are temporary transitional periods in which typical features for a specific behavioral state are incomplete. These transitional sleep states typically blend together clinical and EEG features of the original and final behavioral states. Transitional sleep does not clearly satisfy the polysomnographic and EEG background criteria for a specific state, as defined above. For example, in the transition from active sleep to quiet sleep, an infant might still show some large body movement but deep regular respirations accompanied by an EEG that is between activité moyenne and tracé alternant. This admixture of the two states is seen until quiet sleep fully emerges and satisfies all the criteria for definite quiet sleep. Transitional sleep can be thought of as a temporary period of indeterminate sleep, as described below. Indeterminate Sleep Segments of the EEG in which the baby's eyes are closed (indicating sleep) but in which other clinical and EEG features do not permit definite assignment to active or quiet sleep are designated as indeterminate sleep. These periods lack the anticipated features for assignment to a unique sleep state. As above, transitional sleep is a temporary kind of indeterminate sleep. Much of the sleep is indeterminate in very preterm infants in whom there is not a well-established concordance between the EEG background and polysomnographic variables. Only a small amount of total sleep time is indeterminate in healthy term infants. A high percentage of total sleep time that is indeterminate would be considered abnormal at term. Sleep–Wake Cycling Sleep–wake cycling is the pattern of alterations among behavioral states. Cycling is more distinctive and easier to recognize in term babies, compared with preterm babies. It is also easier to detect in long-term recordings than brief routine tracings (Scher et al., 2005a). Term. In the term infant, a complete sleep and waking cycle typically has a duration of 3 to 4 hours (Scher et al., 2005b). An isolated sleep-only cycle typically lasts 40 to 70 minutes and progresses in a somewhat orderly fashion. The awake term infant usually first falls into an active sleep state. This is true until about 4 months after term equivalent age. Tracé alternant may then appear in the first portion of quiet sleep and gradually be replaced by continuous high-voltage slow activity. Term neonates spend approximately 50% to 60% of the sleep cycle in active sleep, 30% to 40% in quiet sleep, and 10% to 15% in transitional sleep. Preterm. The proportion of time spent in any state also varies by age (Curzi-Dascalova et al., 1988; Scher et al., 2005a). The first rudimentary evidence of sleep cycling can be seen at 25 weeks of PMA. At 27 to 34 weeks of PMA, 40% to 45% is spent in active sleep, 25% to 30% in quiet sleep, and 30% in indeterminate sleep. Beyond 35 weeks of PMA, infants spend 55% to 65% of the time in active sleep, 20% in quiet sleep, and 10% to 15% in indeterminate sleep. The duration of a sleep cycle (first active sleep, then transitional sleep and finally quiet sleep) is 30 to 50 minutes for neonates <35 weeks of PMA and increases to 50 to 65 minutes beyond 35 weeks of PMA. Unspecified state changes. In a sick infant with disruption of normal background features, it may be difficult or impossible to identify definite specific sleep states. However, some infants can still have state changes, defined as cycling between distinctly different EEG patterns as indicated by the amount of background discontinuity, voltages, or electrical frequencies with at least 1 minute in each unspecified state. EEG BACKGROUND The constituents of normal neonatal EEG background evolve with PMA. In the following section, the features of both normal and abnormal EEG backgrounds will be defined (Table 3).TABLE 3: EEG BackgroundContinuity Normal Continuity EEG activity is continuous when there is uninterrupted, nonstop electrical activity with <2 seconds of voltage attenuation <25 µV pp. The entire evolution of the normal EEG background proceeds from the persistently discontinuous tracing in all behavioral states in extremely premature infants to continuous EEG in all states in fully mature infants. Discontinuity Discontinuous EEG activity is broadly recognized as higher voltage “bursts” of electrical activity interrupted by lower voltage “interbursts.” The intervening periods of attenuation are termed interburst intervals (IBI). The durations in seconds of the IBIs are a function of age, being longest in very preterm infants and shortest during tracé alternant quiet sleep at term. We define the IBI as a period in which activity is attenuated <25 to 50 µV pp for 2 seconds or more. The literature has historically proposed various definitions for classifying EEG patterns on the basis of IBI. The definitions offered here are attempted compromises from these (Hahn et al., 1989; Lamblin et al., 1999) (Table 4). The background can still be called discontinuous if there is modest activity within the IBI in a single electrode or a single transient in multiple electrodes.TABLE 4: Normal IBI Duration and AmplitudeNormal Discontinuity There is a progressive decrease in normal IBI durations with increasing PMA (Hahn et al., 1989; Lamblin et al., 1999). Tracé discontinu, as defined above, is a normal discontinuous EEG pattern in preterm infants (Figs. 1, 2A). The electrical activity within the bursts includes age-appropriate graphoelements such as rhythmic occipital delta activity and other specific, named patterns that are described below. It is present in varying amounts from 26 to 40 weeks of PMA. It appears first in wakefulness, active and quiet sleep (until 30 weeks of PMA), then only in quiet sleep and is rarely seen in infants of 38-week PMA or older (Hahn et al., 1989). Tracé alternant, as already defined, depicts a point of transition from complete discontinuity to full continuity. It is only seen in quiet sleep. In the transition from tracé discontinu to tracé alternant, the durations of the IBIs shorten while their voltages swell until all the gaps of immature discontinuity have been filled in. While bursts of 50 to 150 µV delta activity alternate with lower voltage theta activity of 25 to 50 µV, these lower voltage periods never completely attenuate. In contrast to tracé discontinu, the voltages are never <25 µV pp (Lamblin et al., 1999) (Figs. 1, 2B). Like tracé discontinu, the abundance of this pattern varies by age. Tracé alternant is first seen at 34 to 36 weeks of PMA, which becomes minimal by 42 weeks and is no longer seen by 46 weeks of PMA. Excessive Background Discontinuity In sick newborn infants who have experienced a variety of causes of encephalopathy (such as HIE, intracerebral bleeding, septic meningitis, etc.), the two main reported categories of background abnormalities are pathologically excessive discontinuity and abnormally low voltage for PMA (Clancy et al., 2011). We suggest restricting the term “excessive discontinuity” to abnormally discontinuous tracings with bursts that contain some normal patterns and graphoelements separated by IBIs that are too prolonged or voltage depressed for PMA, as defined by the parameters in Table 4 (Figs. 1, 2C) (Clancy and Wusthoff, 2011). This is an area that can be addressed and better quantified by future study using standardized methodology to correlate IBI with patient outcomes. Burst Suppression Further disruption of EEG continuity results in the more severe burst suppression pattern. This consists of invariant, abnormally composed EEG bursts separated by prolonged and abnormally low voltage IBIs periods, strictly defined as IBI voltages <5 µV pp (Figs. 1, 2D). However, the definition does allow for one electrode with sparse activity during the IBI up to 15 µV pp or less than 2 seconds with transient activity up to 15 µV pp or >2:1 asymmetry in voltage in multiple electrodes. In all cases, the EEG should be invariant, with no spontaneous discontinuity changes because of internally mediated lability and no EEG change of reactivity because of external noxious stimulation of the infant. The presence of high (>100 µV pp) or low (<100 µV pp) voltage activity in the bursts should be described. The composition of the bursts of the EEG activity is characterized by nonspecific theta, delta, beta, and admixed sharp waves but is devoid of specific graphoelements such as monorhythmic occipital delta activity, delta brushes, or other recognizable graphoelements. This is a key feature distinguishing burst suppression from excess discontinuity: burst suppression has no normal features within the bursts, whereas excessively discontinuous records have some normal patterns identifiable within the bursts. Similarly, burst suppression is an invariant pattern, whereas excess discontinuity contains some variability or reactivity. If burst suppression typical burst and IBI duration should be Further characterization should include a of the of the of a typical burst and and of In some the bursts are composed of nonspecific but in sharp waves appear admixed within the bursts. Normal In the normal neonatal electrical voltages, and the of specific, named graphoelements should be between of the two The and should be more or less of each This for transient to while still considering the record The of more than a difference in voltages between of the two or a of background features, the electrical frequencies and the of specific graphoelements between the two is abnormal. bleeding, for up to 10% of acute neonatal EEG background are not and may be is defined as the onset of bursts of activity that occur between in the discontinuous portions of the recording. For example, a single burst within tracé discontinu would be considered if the of the and bursts occur within seconds of each The the percentage of bursts that are within the discontinuous portions of the Normal The percentage of bursts is not a function of PMA. 27 to weeks of PMA, EEG activity is completely (Clancy et al., et al., and 30 weeks of PMA, EEG activity may only be approximately approximately 30 to 37 weeks of PMA, more activity emerges until term when the EEG is Normal As above, some of is expected and normal between 30 and 37 weeks of PMA. By weeks of PMA, the EEG should not show any amount of This is defined as a clearly excessive percentage of EEG bursts for PMA that occur than seconds between the onset of activity in each during the discontinuous portions of the recording. studies have defined the normal for voltage (or in premature infants. there will be no to normal voltage criteria for in this The focus of this will be the of normal voltage for the term infant (Fig. 1). as with the older child or adult, voltage abnormalities should be interpreted with because many (such as electrode or electrode and can result in low voltage EEG activity or voltage voltage are difficult to Normal A healthy term infant should have most EEG activity µV pp in all behavioral states. This is defined as a continuous EEG background some normal activity and graphoelements with voltages persistently at least 10 µV but <25 The clinical significance of low voltage is not voltage suppressed. There are various definitions in the literature of an abnormal background because of a low voltage or voltage pattern et al., et al., et al., We a definition of persistently low voltage activity without normal background features. The voltage is µV pp. The background can be with higher voltage µV pp) transient activity for <2 In the record is invariant, with no and with no EEG changes from external This pattern severe neurologic with or of the cortical of EEG activity. This terminology is used to describe the absence of cerebral electrical activity µV pp when at a of 2 and The term has replaced the terms and recordings, although their are the guidelines the technical for an EEG to for Clinical Neurophysiology These are from the technical for neonatal EEG recordings. If the EEG is not to these the term should not be If there is no cerebral activity, but the recording not to the the report should that the recording may be with but should that cannot be without the technical is a pattern when with clinical is used to determine cerebral 1989; and 1989; and et al., are to their guidelines regarding the of brain for newborn as conspicuous spontaneous EEG to such as that occur during typical sleep–wake It is first present by 25 weeks when the EEG changes with state. should be by 28 weeks of PMA and by 30 to 31 weeks of PMA. The EEG can of changes in any electrical or It is to note that from sleep can result in transient attenuation of EEG voltages, which should not be for should be recorded as or For example, variability would be present in a recording, which multiple behavioral states such as wakefulness, transitional, active, and quiet sleep. The last might for example, in a recording that only an awake state. of EEG is when there is a conspicuous cerebral EEG to external Like these EEG also of changes in any electrical or The clinical and behavioral of reactivity can include movement, EMG activity, and respiratory pattern changes. It is to note that after or external behavioral may artifacts from movement or EMG activity that may changes of the EEG first appears at 30 to 32 weeks of PMA, but it might not been seen with each and external should be recorded as or of should be noted. The in which the term very premature infants with such as their EEG background features to mature at the same as their PMA There a between their PMA and their as by the of their EEG This in between the PMA and their is termed defined as an EEG that would be normal for an infant at least 2 weeks than the PMA. The persistently EEG is considered abnormal and is with an risk of abnormal neurologic et al., and BACKGROUND In neonatal graphoelements are and named EEG background patterns that first appear and then during particular epochs of neonatal are characteristic of specific are a of the composition of the normal EEG background and are typically of specific is included we have defined the most seen (Table Normal This pattern occurs between and 34 weeks of PMA and consists of high voltage to µV pp) delta activity with a

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