Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic.

An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic—“live microorganisms which when administered in adequate amounts confer a health benefit on the host”—was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.

Large variability of proanthocyanidin content and composition in sainfoin (onobrychis viciifolia)

Proanthocyanidins (PAs) in sainfoin (Onobrychis viciifolia Scop.) are of interest to ameliorate the sustainability of livestock production. However, sainfoin forage yield and PA concentrations, as well as their composition, require optimization. Individual plants of 27 sainfoin accessions from four continents were analyzed with LC-ESI-QqQ-MS/MS for PA concentrations and simple phenolic compounds. Large variability existed in PA concentrations (23.0–47.5 mg g–1 leaf dry matter (DM)), share of prodelphinidins (79–96%), and mean degree of polymerization (11–14) among, but also within, accessions. PAs were mainly located in leaves (26.8 mg g–1 DM), whereas stems had less PAs (7.8 mg g–1 DM). Overall, high-yielding plants had lower PA leaf concentrations (R2 = 0.16, P < 0.001) and fewer leaves (R2 = 0.66, P < 0.001). However, the results show that these two trade-offs between yield and bioactive PAs can be overcome.

Binding of an oligomeric ellagitannin series to bovine serum albumin (BSA): analysis by isothermal titration calorimetry (ITC)

A unique series of oligomeric ellagitannins was used to study their interactions with bovine serum albumin (BSA) by isothermal titration calorimetry. Oligomeric ellagitannins, ranging from monomer to heptamer and a mixture of octamer–undecamers, were isolated as individual pure compounds. This series allowed studying the effects of oligomer size and other structural features. The monomeric to trimeric ellagitannins deviated most from the overall trends. The interactions of ellagitannin oligomers from tetramers to octa–undecamers with BSA revealed strong similarities. In contrast to the equilibrium binding constant, enthalpy showed an increasing trend from the dimer to larger oligomers. It is likely that first the macrocyclic part of the ellagitannin binds to the defined binding sites on the protein surface and then the “flexible tail” of the ellagitannin coats the protein surface. The results highlight the importance of molecular flexibility to maximize binding between the ellagitannin and protein surfaces.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.2014

Programa postural para escolares do ensino fundamental

É sabido que crianças e adolescentes podem ser acometidas de dor nas costas de forma aguda ou até mesmo crônica (SALMINEN, PENTTI E TERHO, 1992; KRISTJÁNDÓTTIR, 1996; WEDDERKOPP et al. 2001). Essa ocorrência muitas vezes está associada às atividades escolares que fazem parte do cotidiano desta população (SOUZA, ÁVILA E MORO, 1999; GRIMMER E WILLIAMS, 2000). Os programas de prevenção, baseados nos princípios da Escola Postural (SOUZA, 1996), podem ser uma alternativa para minimizar os efeitos provocados pela repetição excessiva dos movimentos, na medida em que os discute e pratica de forma biomecanicamente adaptada a sua realidade (MÉNDEZ E GÓMEZ-CONESA, 2001; CARDON, DE CLERCQ E BOURDEAUDHUIJ, 2002). Este trabalho situa-se nessa perspectiva. Seu objetivo foi verificar a influência do Programa Postural para Escolares do Ensino Fundamental na (1) execução e (2) aplicação das Atividades de Vida Diária (AVD’S) dos escolares, na (3) forma como percebem e justificam suas posturas frente a algumas tarefas escolares cotidianas e na (4) Amplitude de Movimento Articular do tornozelo, quadril e coluna lombar. A amostra foi composta de um grupo controle (n=29; idade média=15,38 anos ±0,97) e um grupo experimental (n=32; idade média=14 anos ±0,93), selecionados intencionalmente. O Programa postural consistiu em vinte encontros de 50 minutos cada, duas vezes por semana. Os encontros eram teórico-práticos e abordavam as atividades de vida diária relacionadas ao cotidiano escolar: sentar, permanecer sentado, permanecer sentado para escrever em sala de aula, transportar o material escolar e pegar objetos leves e pesados do chão Foram seis os instrumentos utilizados para avaliar o programa: (1) Observação das Atividades de Vida Diária através de Vídeo (ROCHA e SOUZA, 1999); (2) Questionário sobre as Atividades de Vida Diária – Versão para os Escolares; (3) Observação da Postura Sentada para Escrever em Sala de Aula; (4) Questionário sobre as Atividades de Vida Diária – Versão para os Pais; (5) Entrevista sobre as respostas dos escolares ao seus questionários sobre as AVD’S e (6) mensuração da Amplitude de Movimento Articular do tornozelo, quadril e coluna lombar. Os grupos realizaram todas as avaliações tanto no pré-teste quanto no pós-teste mas apenas o grupo experimental participou do programa postural. Os resultados mostraram que o Programa Postural influenciou significativamente o grupo experimental nas Atividades de Vida Diária (Instrumento 1; p≤0,004), nas tarefas de sentar e sentar para escrever (Instrumento 2; p≤0,02) e na postura sentada para escrever em sala de aula (Instrumento 3; p=0,001). Além disso, as respostas dos alunos às entrevistas mostraram que houve modificação qualitativa na forma de analisar as posições assumidas no ambiente escolar. Não foi observada influência estatisticamente significativa do Programa no questionário sobre as atividades de vida diária – versão para os pais (Instrumento 4) e na avaliação das amplitudes de movimento articular (Instrumento 6). Concluiu-se com este estudo que o Programa Postural para Escolares do Ensino Fundamental foi eficiente na melhoria da execução das AVD’s dos participantes, especialmente nos atos de sentar e permanecer sentado para escrever, assim como, na aplicação da postura sentada para escrever em sala de aula.

Ten years of NO2 comparisons between ground-based SAOZ and satellite instruments (GOME, SCIAMACHY, OMI)

SAOZ (Systeme d'Analyse par Observations Zenithales) is a ground-based UV-Visible zenith-sky spectrometer installed between 1988 and 1995 at a number of NDSC stations at various latitudes on the globe. The instrument is providing ozone and NO2 vertical columns at sunrise and sunset using the Differential Optical Absorption Spectroscopy (DOAS) technique in the visible spectral range. The ERS-2 GOME Ozone Monitoring Experiment (GOME) in 1995 was the first satellite mission to provide a global picture of atmospheric NO 2 with reasonable spatial and temporal resolution. It was then followed by SCanning ImAging spectroMeter for Atmospheric ChartographY (SCIAMACHY) onboard ENVISAT in 2002, and Ozone Monitoring Instrument (OMI) onboard EOS-AURA in 2004, with a similar capacity to monitor total NO 2. All these instruments are nadir viewing mapping spectrometers, applying the DOAS technique in the visible for deriving the NO2 total column. Here we present the results of NO2 long-term comparisons between GOME and SAOZ for the whole period of GOME operation since 1995 at all latitudes - tropics, mid-latitudes and polar regions - in both hemispheres. Comparisons are also shown with the most recently available SCIAMACHY and OMI data in 2004-2005. Overall, the daytime satellite measurements (around noon) are found consistent with sunrise ground-based data, with an average smaller difference at the tropics and mid-latitudes than in the polar areas in the summer. The agreement is even improved after correcting for the NO2 photochemical change between sunrise and the satellite overpass using a box model. However, some seasonal dependence of the difference between ground-based and satellite total NO2 still remains, related to the accuracy of photochemical simulations and the set of NO2 air mass factors used in the retrievals of both systems.

Current approach to the haemodynamic management of septic shock patients in European intensive care units: a cross-sectional, self-reported questionnaire-based survey

The aim of this survey was to investigate clinicians' current approach to the haemodynamic management and resuscitation endpoints in septic shock.

Early non-invasive cardiac output monitoring in hemodynamically unstable intensive care patients: A multi-center randomized controlled trial

Introduction Acute hemodynamic instability increases morbidity and mortality. We investigated whether early non-invasive cardiac output monitoring enhances hemodynamic stabilization and improves outcome. Methods A multicenter, randomized controlled trial was conducted in three European university hospital intensive care units in 2006 and 2007. A total of 388 hemodynamically unstable patients identified during their first six hours in the intensive care unit (ICU) were randomized to receive either non-invasive cardiac output monitoring for 24 hrs (minimally invasive cardiac output/MICO group; n = 201) or usual care (control group; n = 187). The main outcome measure was the proportion of patients achieving hemodynamic stability within six hours of starting the study. Results The number of hemodynamic instability criteria at baseline (MICO group mean 2.0 (SD 1.0), control group 1.8 (1.0); P = .06) and severity of illness (SAPS II score; MICO group 48 (18), control group 48 (15); P = .86)) were similar. At 6 hrs, 45 patients (22%) in the MICO group and 52 patients (28%) in the control group were hemodynamically stable (mean difference 5%; 95% confidence interval of the difference -3 to 14%; P = .24). Hemodynamic support with fluids and vasoactive drugs, and pulmonary artery catheter use (MICO group: 19%, control group: 26%; P = .11) were similar in the two groups. The median length of ICU stay was 2.0 (interquartile range 1.2 to 4.6) days in the MICO group and 2.5 (1.1 to 5.0) days in the control group (P = .38). The hospital mortality was 26% in the MICO group and 21% in the control group (P = .34). Conclusions Minimally-invasive cardiac output monitoring added to usual care does not facilitate early hemodynamic stabilization in the ICU, nor does it alter the hemodynamic support or outcome. Our results emphasize the need to evaluate technologies used to measure stroke volume and cardiac output--especially their impact on the process of care--before any large-scale outcome studies are attempted.

Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials

Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α(2)-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort.

TONOMETRY REVISITED: PERFUSION-RELATED, METABOLIC, AND RESPIRATORY COMPONENTS OF GASTRIC MUCOSAL ACIDOSIS IN ACUTE CARDIORESPIRATORY FAILURE

Mucosal pH (pHi) is influenced by local perfusion and metabolism (mucosal-arterial Pco2 gradient, DeltaPco2), systemic metabolic acidosis (arterial bicarbonate), and respiration (arterial Pco2). We determined these components of pHi and their relation to outcome during the first 24 h of intensive care. We studied 103 patients with acute respiratory or circulatory failure (age, 63 +/- 2 [mean +/- SEM]; Acute Physiology and Chronic Health Evaluation II score, 20 +/- 1; Sequential Organ Failure Assessment score, 8 +/- 0). pHi, and the effects of bicarbonate and arterial and mucosal Pco2 on pHi, were assessed at admission, 6, and 24 h. pHi was reduced (at admission, 7.27 +/- 0.01) due to low arterial bicarbonate and increased DeltaPco2. Low pHi (<7.32) at admission (n = 58; mortality, 29% vs. 13% in those with pHi >/=7.32 at admission; P = 0.061) was associated with an increased DeltaPco2 in 59% of patients (mortality, 47% vs. 4% for patients with low pHi and normal DeltaPco2; P = 0.0003). An increased versus normal DeltaPco2, regardless of pHi, was associated with increased mortality at admission (51% vs. 5%; P < 0.0001; n = 39) and at 6 h (34% vs. 13%; P = 0.016; n = 45). A delayed normalization or persistently low pHi (n = 47) or high DeltaPco2 (n = 25) was associated with high mortality (low pHi [34%] vs. high DeltaPco2 [60%]; P = 0.046). In nonsurvivors, hypocapnia increased pHi at baseline, 6, and 24 h (all P

Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation

PURPOSE: To compare dexmedetomidine (DEX) with standard care (SC, either propofol or midazolam) for long-term sedation in terms of maintaining target sedation and length of intensive care unit (ICU) stay. METHODS: A pilot, phase III, double-blind multicenter study in randomized medical and surgical patients (n = 85) within the first 72 h of ICU stay with an expected ICU stay of >or=48 h and sedation need for >or=24 h after randomization. Patients were assigned to either DEX (

Development and simultaneous application of multiple care protocols in critical care: a multicenter feasibility study

OBJECTIVE: To test the feasibility of and interactions among three software-driven critical care protocols. DESIGN: Prospective cohort study. SETTING: Intensive care units in six European and American university hospitals. PATIENTS: 174 cardiac surgery and 41 septic patients. INTERVENTIONS: Application of software-driven protocols for cardiovascular management, sedation, and weaning during the first 7 days of intensive care. MEASUREMENTS AND RESULTS: All protocols were used simultaneously in 85% of the cardiac surgery and 44% of the septic patients, and any one of the protocols was used for 73 and 44% of study duration, respectively. Protocol use was discontinued in 12% of patients by the treating clinician and in 6% for technical/administrative reasons. The number of protocol steps per unit of time was similar in the two diagnostic groups (n.s. for all protocols). Initial hemodynamic stability (a protocol target) was achieved in 26+/-18 min (mean+/-SD) in cardiac surgery and in 24+/-18 min in septic patients. Sedation targets were reached in 2.4+/-0.2h in cardiac surgery and in 3.6 +/-0.2h in septic patients. Weaning protocol was started in 164 (94%; 154 extubated) cardiac surgery and in 25 (60%; 9 extubated) septic patients. The median (interquartile range) time from starting weaning to extubation (a protocol target) was 89 min (range 44-154 min) for the cardiac surgery patients and 96 min (range 56-205 min) for the septic patients. CONCLUSIONS: Multiple software-driven treatment protocols can be simultaneously applied with high acceptance and rapid achievement of primary treatment goals. Time to reach these primary goals may provide a performance indicator.

Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial

INTRODUCTION: It is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock. METHODS: This is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP > or = 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles > or = 70 mmHg and mortality or the frequency and occurrence of disease-related events. RESULTS: There was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.28-2.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.38-2.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01). CONCLUSIONS: MAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. Elevating MAP >70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.

Increased splanchnic oxygen extraction because of routine nursing procedures

OBJECTIVE: Multiple organ failure is a common complication of acute circulatory and respiratory failure. We hypothesized that therapeutic interventions used routinely in intensive care can interfere with the perfusion of the gut and the liver, and thereby increase the risk of mismatch between oxygen supply and demand. DESIGN: Prospective, observational study. SETTING: Interdisciplinary intensive care unit (ICU) of a university hospital. PATIENTS: Thirty-six patients on mechanical ventilation with acute respiratory or circulatory failure or severe infection were included. INTERVENTIONS: Insertion of a hepatic venous catheter. MEASUREMENTS AND MAIN RESULTS: Daily nursing procedures were recorded. A decrease of >or=5% in hepatic venous oxygen saturation (Sho2) was considered relevant. Observation time was 64 (29-104) hours (median [interquartile range]). The ICU stay was 11 (8-15) days, and hospital mortality was 35%. The number of periods with procedures/patient was 170 (98-268), the number of procedure-related decreases in Sho2 was 29 (13-41), and the number of decreases in Sho2 unrelated to procedures was 9 (4-19). Accordingly, procedure-related Sho2 decreases occurred 11 (7-17) times per day. Median Sho2 decrease during the procedures was 7 (5-10)%, and median increase in the gradient between mixed and hepatic venous oxygen saturation was 6 (4-9)%. Procedures that caused most Sho2 decreases were airway suctioning, assessment of level of sedation, and changing patients' position. Sho2 decreases were associated with small but significant increases in heart rate and intravascular pressures. Maximal Sequential Organ Failure Assessment scores in the ICU correlated with the number of Sho2 decreases (r: .56; p < 0.001) and with the number of procedure-related Sho2 decreases (r: .60; p < 0.001). CONCLUSIONS: Patients are exposed to repeated episodes of impaired splanchnic perfusion during routine nursing procedures. More research is needed to examine the correlation, if any, between nursing procedures and hepatic venous desaturation.

The effect of projections on dimension in the Heisenberg group

We prove analogs of classical almost sure dimension theorems for Euclidean projection mappings in the first Heisenberg group, equipped with a sub-Riemannian metric.