Yersinia pseudotuberculosis efficiently escapes polymorphonuclear neutrophils during early infection.
The human-pathogenic species of the Gram-negative genus Yersinia preferentially target and inactivate cells of the innate immune defense, suggesting that this is a critical step by which these bacteria avoid elimination and cause disease. In this study, bacterial interactions with dendritic cells, macrophages, and polymorphonuclear neutrophils (PMNs) in intestinal lymphoid tissues during early Yersinia pseudotuberculosis infection were analyzed. Wild-type bacteria were shown to interact mainly with dendritic cells, but not with PMNs, on day 1 postinfection, while avirulent yopH and yopE mutants interacted with PMNs as well as with dendritic cells. To unravel the role of PMNs during the early phase of infection, we depleted mice of PMNs by using an anti-Ly6G antibody, after which we could see more-efficient initial colonization by the wild-type strain as well as by yopH, yopE, and yopK mutants on day 1 postinfection. Dissemination of yopH, yopE, and yopK mutants from the intestinal compartments to mesenteric lymph nodes was faster in PMN-depleted mice than in undepleted mice, emphasizing the importance of effective targeting of PMNs by these Yersinia outer proteins (Yops). In conclusion, escape from interaction with PMNs due to the action of YopH, YopE, and YopK is a key feature of pathogenic Yersinia species that allows colonization and effective dissemination.


Basic anatomical and physiological data for use in radiological protection: reference values. A report of age- and gender-related differences in the anatomical and physiological characteristics of reference individuals. ICRP Publication 89.
This report presents detailed information on age- and gender-related differences in the anatomical and physiological characteristics of reference individuals. These reference values provide needed input to prospective dosimetry calculations for radiation protection purposes for both workers and members of the general public. The purpose of this report is to consolidate and unify in one publication, important new information on reference anatomical and physiological values that has become available since Publication 23 was published by the ICRP in 1975. There are two aspects of this work. The first is to revise and extend the information in Publication 23 as appropriate. The second is to provide additional information on individual variation among grossly normal individuals resulting from differences in age, gender, race, or other factors. This publication collects, unifies, and expands the updated ICRP reference values for the purpose of providing a comprehensive and consistent set of age- and gender-specific reference values for anatomical and physiological features of the human body pertinent to radiation dosimetry. The reference values given in this report are based on: (a) anatomical and physiological information not published before by the ICRP; (b) recent ICRP publications containing reference value information; and (c) information in Publication 23 that is still considered valid and appropriate for radiation protection purposes. Moving from the past emphasis on 'Reference Man', the new report presents a series of reference values for both male and female subjects of six different ages: newborn, 1 year, 5 years, 10 years, 15 years, and adult. In selecting reference values, the Commission has used data on Western Europeans and North Americans because these populations have been well studied with respect to antomy, body composition, and physiology. When appropriate, comparisons are made between the chosen reference values and data from several Asian populations. The first section of the report provides summary tables of all the anatomical and physiological parameters given as reference values in this publication. These results give a comprehensive view of reference values for an individual as influenced by age and gender. The second section describes characteristics of dosimetric importance for the embryo and fetus. Information is provided on the development of the total body and the timing of appearance and development of the various organ systems. Reference values are provided on the mass of the total body and selected organs and tissues, as well as a number of physiological parameters. The third section deals with reference values of important anatomical and physiological characteristics of reference individuals from birth to adulthood. This section begins with details on the growth and composition of the total body in males and females. It then describes and quantifies anatomical and physiological characteristics of various organ systems and changes in these characteristics during growth, maturity, and pregnancy. Reference values are specified for characteristics of dosimetric importance. The final section gives a brief summary of the elemental composition of individuals. Focusing on the elements of dosimetric importance, information is presented on the body content of 13 elements: calcium, carbon, chloride, hydrogen, iodine, iron, magnesium, nitrogen, oxygen, potassium, sodium, sulphur, and phosphorus.


Arterial Stiffness Is Reduced Regardless of Resistance Training Load in Young Men.
Discrepancies regarding the effect of resistance exercise training (RET) on arterial stiffness have led to uncertainty regarding the effect of RET on cardiovascular health. Confounding our understanding in this area are the roles of the following: load (heavier vs lighter), participant cardiovascular health, and arterial stiffness assessment method. We aimed to investigate the effects of a heavier versus a lighter load resistance training protocol on both central and local arterial stiffness in previously trained young men. Participants were randomly assigned to a 12-wk supervised whole-body RET program consisting of three sets of 8-12 repetitions (heavier-load, lower-repetition [LR]; n = 16) or three sets of 20-25 repetitions (lighter-load, higher-repetition [HR]; n = 16) to volitional failure, or a control group who maintained their regular activity habits (n = 14). Central arterial stiffness (carotid-femoral pulse wave velocity), local arterial stiffness (common carotid arterial distensibility), and left ventricular mass were measured before and after 12 wk of RET. There was a reduction in carotid-femoral pulse wave velocity in both LR (6.24 ± 0.56 vs 5.77 ± 0.76 m·s; P < 0.05) and HR (6.42 ± 0.70 vs 5.72 ± 0.60 m·s; P < 0.05) with no changes in carotid distensibility (P = 0.52) or left ventricular mass allometrically scaled to fat-free mass (P = 0.60). There were no changes in any variable in the control group. Using current criterion-standard assessment methods, central arterial stiffness was reduced after resistance training, regardless of the load lifted during RET, with no effect on local carotid artery distensibility or left ventricular mass. Our results support a role of RET in the promotion of positive adaptations in vascular function.


The Unique Antimicrobial Recognition and Signaling Pathways in Tardigrades with a Comparison Across Ecdysozoa.
Tardigrades are microscopic animals known to withstand unfavorable abiotic conditions. These animals are also constantly exposed to biotic stresses, including parasites and internal microbiomes. However, the tardigrade immune mechanisms against these biotic stresses are largely uncharacterized. Due to the contentious phylogenetic position of tardigrades, it is not intuitive whether they possess an immune system more similar to that of arthropods (e.g., Toll, Imd, and JNK pathways of the Drosophila melanogaster antimicrobial response) or to that of nematodes (e.g., the Tir-1/Nsy-1/Sek-1/Pmk-1/Atf-7 signaling cassette [called Tir-1 pathway here]) in Caenorhabditis elegans). In this study, comparative genomic analyses were conducted to mine homologs of canonical D. melanogaster and C. elegans immune pathway genes from eight tardigrades (Echiniscoides cf. sigismundi, Echiniscus testudo, Hypsibius exemplaris, Mesobiotus philippinicus, Milnesium tardigradum, Paramacrobiotus richtersi, Richtersius cf. coronifer, and Ramazzottius varieornatus) and four non-arthropod ecdysozoans (two onychophorans: Epiperipatus sp. and Opisthopatus kwazululandi; one nematomorph: Paragordius varius; and one priapulan: Priapulus caudatus) in order to provide insights into the tardigrade antimicrobial system. No homologs of the intracellular components of the Toll pathway were detected in any of the tardigrades examined. Likewise, no homologs of most of the Imd pathway genes were detected in any of the tardigrades or any of the other non-arthropod ecdysozoans. Both the JNK and Tir-1 pathways, on the other hand, were found to be conserved across ecdysozoans. Interestingly, tardigrades had no detectable homologs of NF-κB, the major activator of antimicrobial response gene expression. Instead, tardigrades appear to possess NF-κB distantly related NFAT homologs. Overall, our results show that tardigrades have a unique gene pathway repertoire that differs from that of other ecdysozoans. Our study also provides a framework for future studies on tardigrade immune responses.


In vivo visualization of activated glia by [11C] (R)-PK11195-PET following herpes encephalitis reveals projected neuronal damage beyond the primary focal lesion.
A major challenge in the assessment of brain injury and its relationship to the ensuing functional deficits is the accurate delineation of the areas of damage. Here, we test the hypothesis that the anatomical distribution pattern of activated microglia, a normally dormant population of resident brain macrophages, can be used as a surrogate marker of neuronal injury not only at the primary lesion site but also in the antero- and retrograde projection areas of the lesioned neurones. Two patients with asymmetrical herpes simplex encephalitis were serially scanned 6 and 12 months after the acute illness using PET with [11C] (R)-PK11195, a marker of activated microglia/brain macrophages. The evolving structural changes in the brain were measured by volumetric MRI and compared with the pattern of [11C](R)-PK11195 binding. Corresponding to the clinically observed cognitive deficits, quantitative [11C](R)-PK11195-PET revealed highly significant signal increases within the affected limbic system and additionally in areas connected to the limbic system by neural pathways, including the lingual gyrus in the occipital lobe and the inferior parietal lobe, which had normal morphology on structural MRI. The increased [11C](R)-PK11195 binding, signifying the presence of activated microglia, persisted many months (>12) after antiviral treatment. Cortical areas that showed early high [11C](R)-PK11195 binding subsequently underwent atrophy. These observations demonstrate that in vivo imaging of activated microglia/brain macrophages provides a dynamic measure of active tissue changes following an acute focal lesion. Importantly, the glial tissue response in the wake of neuronal damage is protracted and widespread within the confines of the affected distributed neural system and can be related to the long-term functional deficits.


Prevalence of autism and parentally reported triggers in a north east London population.
The recorded prevalence of autistic spectrum disorders has risen over recent decades. Measles, mumps and rubella (MMR) vaccine has been blamed, by causing a "new variant" form of "regressive autism" associated with "autistic enterocolitis". To estimate the prevalence of autism and to assess any changes in parental perception regarding the onset or causes of autism. A total of 567 children with autistic spectrum disorder in five districts in north east London were identified, born 1979-98. Reported autism, excluding the 94 cases of Asperger's syndrome, increased by year of birth until 1992, since when prevalence has plateaued. This flattening off persisted after allowing for expected delay in diagnosis in more recent birth cohorts. The age at diagnosis of autistic spectrum disorder was estimated to have decreased per five year period since 1983, by 8.7% for childhood autism and by 11.0% for atypical autism. There was some evidence that MMR was more likely to be mentioned as a trigger after August 1997 than before. The prevalence of autism, which was apparently rising from 1979 to 1992, reached a plateau from 1992 to 1996 at a rate of some 2.6 per 1000 live births. This levelling off, together with the reducing age at diagnosis, suggests that the earlier recorded rise in prevalence was not a real increase but was likely due to factors such as increased recognition, a greater willingness on the part of educationalists and families to accept the diagnostic label, and better recording systems. The proportion of parents attributing their child's autism to MMR appears to have increased since August 1997.


Developing a model of best practice for teams managing crisis in people with dementia: a consensus approach.
Teams delivering crisis resolution services for people with dementia and their carers provide short-term interventions to prevent admission to acute care settings. There is great variation in these services across the UK. This article reports on a consensus process undertaken to devise a Best Practice Model and evaluation Tool for use with teams managing crisis in dementia. The Best Practice Model and Tool were developed over a three stage process: (i) Evidence gathering and generation of candidate standards (systematic review and scoping survey, interviews and focus groups); (ii) Prioritisation and selection of standards (consultation groups, a consensus conference and modified Delphi process); (iii) Refining and operationalising standards (consultation group and field-testing). One hundred sixty-five candidate standards arose from the evidence gathering stage; were refined and reduced to 90 through a consultation group exercise; and then reduced to 50 during the consensus conference and weighted using a modified Delphi process. Standards were then operationalised through a clinical consultation group and field-tested with 11 crisis teams and 5 non-crisis teams. Scores ranged from 48 to 92/100. The median score for the crisis teams was 74.5 (range 67-92), and the median score for non-crisis teams was 60 (range 48-72). With further psychometric testing, this Best Practice Model and Tool will be ideal for the planning, improvement and national benchmarking of teams managing dementia crises in the future.


Proguanil resistance in Plasmodium falciparum African isolates: assessment by mutation-specific polymerase chain reaction and in vitro susceptibility testing.
The antifolate proguanil is commonly used in the prophylaxis and treatment of Plasmodium falciparum malaria. A series of point mutations in the dihydrofolate reductase (DHFR) gene has been linked to differential susceptibility of varied P. falciparum clones or isolates to this drug. To survey the efficiency of proguanil prophylaxis in an African endemic region, and to evaluate the level of proguanil resistance in the corresponding parasite population, we performed drug susceptibility assays with P. falciparum isolates from Senegal, Kenya, and Niger. In parallel, we developed a mutation-specific polymerase chain reaction assay that enabled us to characterize mutations in the DHFR gene of the same isolates without in vitro parasite cultivation. We confirm previously available data showing that parasites harboring a point mutation from Ser108 to Asn present a decrease in susceptibility to cycloguanil (the active metabolite of proguanil), and we show that mutations in codons 51 and 59 appear to modulate the level of resistance to cycloguanil. No mutations in codons 16 and 164 were detected in resistant parasites, in contrast with results from some previous studies.


Effects of cardiac contraction and coronary sinus pressure elevation on collateral circulation.
Controlled coronary sinus occlusion was shown to retard necrosis of ischemic myocardium. To elucidate this mechanism, regional myocardial blood flow measurement was performed with and without coronary sinus pressure elevation to 30 mmHg (CS30). Colored microspheres were injected into left and right coronary arteries after coronary perfusion of the left anterior descending (LAD) coronary artery was stopped in seven isolated canine hearts with induced atrioventricular block, either paced at 120 beats/min by direct right ventricular stimulation [beating heart (B)] or during asystole induced by stopping pacing [nonbeating heart (NB)]. Regional myocardial blood flow in the LAD perfused area in the control state in the NB with normal coronary sinus pressure (NB-CScont; 0.27 +/- 0.13 ml.min-1.g-1, means +/- SE) was significantly greater than those in B-CScont (0.19 +/- 0.09 ml.min-1.g-1; P < 0.05) and in NB with CS30 (NB-CS30; 0.19 +/- 0.09 ml.min-1.g-1; P < 0.05). Regional myocardial blood flow of the LAD area in B with CS30 (B-CS30; 0.23 +/- 0.10 ml.min-1.g-1) was significantly greater in comparison with that at B-CScont and NB-CS30 (P < 0.05). The augmentative effect of the LAD area regional myocardial blood flow was observed only in the periphery of the ischemic region but not in its center. Cardiac contraction and CS30 impede regional myocardial blood flow in the ischemic bed independently. The coexistence of these two factors enhances regional myocardial blood flow. In conclusion, coronary sinus pressure elevation in B may participate in augmenting collateral flow.


A Hydrogen-Oxidizing, Fe(III)-Reducing Microorganism from the Great Bay Estuary, New Hampshire.
A dissimilatory Fe(III)- and Mn(IV)-reducing bacterium was isolated from bottom sediments of the Great Bay estuary, New Hampshire. The isolate was a facultatively anaerobic gram-negative rod which did not appear to fit into any previously described genus. It was temporarily designated strain BrY. BrY grew anaerobically in a defined medium with hydrogen or lactate as the electron donor and Fe(III) as the electron acceptor. BrY required citrate, fumarate, or malate as a carbon source for growth on H(2) and Fe(III). With Fe(III) as the sole electron acceptor, BrY metabolized hydrogen to a minimum threshold at least 60-fold lower than the threshold reported for pure cultures of sulfate reducers. This finding supports the hypothesis that when Fe(III) is available, Fe(III) reducers can outcompete sulfate reducers for electron donors. Lactate was incompletely oxidized to acetate and carbon dioxide with Fe(III) as the electron acceptor. Lactate oxidation was also coupled to the reduction of Mn(IV), U(VI), fumarate, thiosulfate, or trimethylamine n-oxide under anaerobic conditions. BrY provides a model for how enzymatic metal reduction by respiratory metal-reducing microorganisms has the potential to contribute to the mobilization of iron and trace metals and to the immobilization of uranium in sediments of Great Bay Estuary.


Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage.
A dose-escalation study of the calcium ion entry blocking drug nicardipine was performed using large dose infusions in 67 patients with recent aneurysmal subarachnoid hemorrhage (SAH). A safe, potentially therapeutic dose of the drug was determined. Patients admitted within 7 days of SAH from a documented cerebral aneurysm were entered into the study if no spasm was present on the initial angiogram. Nicardipine was administered as a continuous intravenous infusion throughout the 14-day period after SAH, regardless of the timing of surgery. To determine the safest possible dose, nicardipine was administered at seven dose levels from 0.01 to 0.15 mg/kg/hr. The total daily doses ranged from 27.7 mg to 375.0 mg. A follow-up angiogram was carried out on all 67 patients 7 to 10 days after SAH. Computerized tomography and neurological examinations were used to determine the presence of cerebral infarction. No major adverse effects, unexpected reactions, or permanent sequelae could be attributed to nicardipine. A decline in blood pressure was noted following administration of the drug. This occurred more frequently among patients given the largest dose but did not produce clinical problems or require discontinuation of the drug. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted: only eight (24%) of 33 patients treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two (6%) of 33 patients treated with this dose. Of the 34 patients receiving the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27%. No deaths due to vasospasm occurred. Nicardipine appears to prevent both vasospasm and cerebral ischemia after SAH. A multicenter randomized double-blind trial to test this hypothesis is planned.


Cluster of Nipah virus infection, Kushtia District, Bangladesh, 2007.
In March 2007, we investigated a cluster of Nipah encephalitis to identify risk factors for Nipah infection in Bangladesh. We defined confirmed Nipah cases by the presence of IgM and IgG antibodies against Nipah virus in serum. Case-patients, who resided in the same village during the outbreak period but died before serum could be collected, were classified as probable cases. We identified three confirmed and five probable Nipah cases. There was a single index case. Five of the secondary cases came in close physical contact to the index case when she was ill. Case-patients were more likely to have physical contact with the index case (71% cases versus 0% controls, p = <0.001). The index case, on her third day of illness, and all the subsequent cases attended the same religious gathering. For three probable cases including the index case, we could not identify any known risk factors for Nipah infection such as physical contact with Nipah case-patients, consumption of raw date palm juice, or contact with sick animals or fruit bats. Though person-to-person transmission remains an important mode of transmission for Nipah infection, we could not confirm the source of infection for three of the probable Nipah case-patients. Continued surveillance and outbreak investigations will help better understand the transmission of Nipah virus and develop preventive strategies.


Booster Breaks in the workplace: participants' perspectives on health-promoting work breaks.
Increasing sedentary work has been associated with greater cardiovascular and metabolic risk, as well as premature mortality. Interrupting the sedentary workday with health-promoting work breaks can counter these negative health effects. To examine the potential sustainability of work-break programs, we assessed the acceptance of these breaks among participants in a Booster Break program. We analyzed qualitative responses from 35 participants across five worksites where one 15-min physical activity break was taken each workday. Two worksites completed a 1-year intervention and three worksites completed a 6-month intervention. Responses to two open-ended questions about the acceptance and feasibility of Booster Breaks were obtained from a survey administered after the intervention. Three themes for benefits and two themes for barriers were identified. The benefit themes were (i) reduced stress and promoted enjoyment, (ii) increased health awareness and facilitated behavior change, and (iii) enhanced workplace social interaction. The barrier themes were the need for (iv) greater variety in Booster Break routines and (v) greater management support. This study provides empirical support for the acceptance and feasibility of Booster Breaks during the workday. Emphasizing the benefits and minimizing the barriers are strategies that can be used to implement Booster Breaks in other workplaces.


Evaluation of quality and patient satisfaction during endoscopic procedure: a cross sectional study from south Asian country.
To assess the quality of gastrointestinal (GI) endoscopic procedures and patient satisfaction in endoscopy suite of South Asian country. Patients coming to the endoscopic suite of Aga Khan University Hospital (AKUH) were interviewed and assessed in this cross-sectional study. Quality of GI endoscopic procedures was evaluated using assessment tools as suggested by The American Society of Gastroenterology. Patient satisfaction after the procedure was assessed using a modified GHAA-9 questionnaire. The questionnaire was statistically evaluated using Pareto analysis and Spearman rank correlation. In this study, 323 patients were evaluated with a mean age of 43 +/- 14.36 years. Out of all the procedures 251 (77.7%) were gastroscopies while 72 (22.3%) were colonoscopies. Patients undergoing different therapeautic procedures were 121 in number (37.46%). Pre-procedure education was rated as excellent or very good by 91.3% of the patients. Midazolam was used for sedation with an average dose of 3 mg. Technically successful procedures included 99.2% gastroscopies and 98.6% colonoscopies. Mean score of patients regarding satisfaction on mGHAA-9 questionnaire was 30 +/- 3.965. Patient dissatisfaction calculated in our study was 3.6% with the length of time spent waiting before procedure and length of time waiting to get an appointment for the procedure contributing to 90% of dissatisfaction. Quality of endoscopic procedures at our centre is at par with international standards with acceptable complication rate and good patient satisfaction.


Photodissociation of OCS: deviations between theory and experiment, and the importance of higher order correlation effects.
The photodissociation of carbonyl sulfide (OCS) was investigated theoretically in a series of studies by Schmidt and co-workers. Initial studies [J. A. Schmidt, M. S. Johnson, G. C. McBane, and R. Schinke, J. Chem. Phys. 136, 131101 (2012); J. A. Schmidt, M. S. Johnson, G. C. McBane, and R. Schinke, J. Chem. Phys. 137, 054313 (2012)] found photodissociation in the first UV-band to occur mainly by excitation of the 2(1)A' (A) excited state. However, in a later study [G. C. McBane, J. A. Schmidt, M. S. Johnson, and R. Schinke, J. Chem. Phys. 138, 094314 (2013)] it was found that a significant fraction of photodissociation must occur by excitation of 1(1)A″ (B) excited state to explain the product angular distribution. The branching between excitation of the A and B excited states is determined by the magnitude of the transition dipole moment vectors in the Franck-Condon region. This study examines the sensitivity of these quantities to changes in the employed electronic structure methodology. This study benchmarks the methodology employed in previous studies against highly correlated electronic structure methods (CC3 and MRAQCC) and provide evidence in support of the picture of the OCS photodissociation process presented in [G. C. McBane, J. A. Schmidt, M. S. Johnson, and R. Schinke, J. Chem. Phys. 138, 094314 (2013)] showing that excitation of A and B electronic states both contribute significantly to the first UV absorption band of OCS. In addition, this study presents evidence in support of the assertion that the A state potential energy surface employed in previous studies underestimates the energy at highly bent geometries (γ ∼ 70°) leading to overestimated rotational energy in the product CO.


Smad3 deficiency in mice protects against insulin resistance and obesity induced by a high-fat diet.
Obesity and associated pathologies are major global health problems. Transforming growth factor-β/Smad3 signaling has been implicated in various metabolic processes, including adipogenesis, insulin expression, and pancreatic β-cell function. However, the systemic effects of Smad3 deficiency on adiposity and insulin resistance in vivo remain elusive. This study investigated the effects of Smad3 deficiency on whole-body glucose and lipid homeostasis and its contribution to the development of obesity and type 2 diabetes. We compared various metabolic profiles of Smad3-knockout and wild-type mice. We also determined the mechanism by which Smad3 deficiency affects the expression of genes involved in adipogenesis and metabolism. Mice were then challenged with a high-fat diet to study the impact of Smad3 deficiency on the development of obesity and insulin resistance. Smad3-knockout mice exhibited diminished adiposity with improved glucose tolerance and insulin sensitivity. Chromatin immunoprecipitation assay revealed that Smad3 deficiency increased CCAAT/enhancer-binding protein β-C/EBP homologous protein 10 interaction and exerted a differential regulation on proliferator-activated receptor β/δ and proliferator-activated receptor γ expression in adipocytes. Focused gene expression profiling revealed an altered expression of genes involved in adipogenesis, lipid accumulation, and fatty acid β-oxidation, indicative of altered adipose physiology. Despite reduced physical activity with no modification in food intake, these mutant mice were resistant to obesity and insulin resistance induced by a high-fat diet. Smad3 is a multifaceted regulator in adipose physiology and the pathogenesis of obesity and type 2 diabetes, suggesting that Smad3 may be a potential target for the treatment of obesity and its associated disorders.


Post-exercise reduction of blood pressure in hypertensive men is not due to acute impairment of baroreflex function.
Two experiments were carried out in male subjects. In the first experiment heart rate and blood pressures were measured before, during and for 90 min after a 50 min period of intermittent exercise in seven hypertensive subjects. After exercise there was a marked reduction in systolic and diastolic blood pressures; this effect lasted throughout the 90 min observation period and was unaccompanied by tachycardia. In the second experiment heart rate and blood pressures were measured before and during the rest periods in a 50 min session of intermittent exercise in nine hypertensive and nine normotensive subjects. Following the first 10 min bout of exercise, resting blood pressures were significantly reduced in the hypertensive subjects; the reduction in blood pressure progressively increased following successive exercise periods. The normotensive subjects did not show a significant reduction in resting blood pressures until the fifth bout of exercise had been completed. In the second experiment also, the competence of baroreflexes was assessed by measuring cardiovascular responses to lower body subatmospheric pressure ( LBSP ) 30 min before and 30 and 60 min after exercise. The post-exercise reduction in blood pressure was not due to exercise-induced impairment of baroreflex mechanisms since the reduced blood pressure after exercise was well maintained during lower body subatmospheric pressure. Furthermore, after exercise, exposure to lower body subatmospheric pressure elicited greater increases in heart rate and forearm vascular resistance than were seen before exercise.


Nut consumption and risk of metabolic syndrome and overweight/obesity: a meta-analysis of prospective cohort studies and randomized trials.
Nut consumption has been shown to reduce the risk of cardiovascular disease. However, its role in the prevention of metabolic disorders, such as metabolic syndrome (Mets) and overweight/obesity, remains controversial. We therefore conducted a meta-analysis to determine the association of nut consumption with Mets and overweight/obesity. Eligible studies were identified by searching the PubMed and Embase databases and by reviewing the references of relevant literatures. We used random effect models to pool the studies-specific risk ratio (RR) and weighted mean difference (WMD). This meta-analysis included six prospective cohort studies with 420,890 subjects and 62 randomized feeding trials with 7184 participants. Among the cohort studies, the summary RR for every 1-serving/week increase in nut intake was 0.96 (95% confidence interval [CI]: 0.92 to 0.99; n = 3) for Mets, 0.97 (95% CI: 0.95 to 0.98; n = 2) for overweight/obesity, and 0.95 (95% CI: 0.89 to 1.02; n = 2) for obesity. Pooling of randomized trials indicated that nut consumption was related to a significant reduction in body weight (WMD: - 0.22 Kg, 95% CI: -0.40 to - 0.04), body mass index (WMD: - 0.16 Kg/m2, 95% CI: -0.31 to - 0.01), and waist circumference (WMD: - 0.51 cm, 95% CI: -0.95 to - 0.07). These findings remained stable in the sensitivity analysis, and no publication bias was detected. Nut consumption may be beneficial in the prevention of Mets and overweight/obesity. Additional prospective studies are needed to enhance these findings and to explore the metabolic benefits for specific subclasses of nut.


Grasses suppress shoot-borne roots to conserve water during drought.
Many important crops are members of the Poaceae family, which develop root systems characterized by a high degree of root initiation from the belowground basal nodes of the shoot, termed the crown. Although this postembryonic shoot-borne root system represents the major conduit for water uptake, little is known about the effect of water availability on its development. Here we demonstrate that in the model C4 grass Setaria viridis, the crown locally senses water availability and suppresses postemergence crown root growth under a water deficit. This response was observed in field and growth room environments and in all grass species tested. Luminescence-based imaging of root systems grown in soil-like media revealed a shift in root growth from crown-derived to primary root-derived branches, suggesting that primary root-dominated architecture can be induced in S. viridis under certain stress conditions. Crown roots of Zea mays and Setaria italica, domesticated relatives of teosinte and S. viridis, respectively, show reduced sensitivity to water deficit, suggesting that this response might have been influenced by human selection. Enhanced water status of maize mutants lacking crown roots suggests that under a water deficit, stronger suppression of crown roots actually may benefit crop productivity.


Healing of segmental bone defects by direct percutaneous gene delivery: effect of vector dose.
Previous studies have demonstrated the ability of direct adenoviral BMP-2 (Ad.BMP-2) gene delivery to enhance bone repair. Nevertheless, in studies using a rat segmental defect model, it has not proved possible to achieve reliably full osseous union in all animals. To address this issue, we evaluated the effect of vector dose on healing. Critical-size defects were created in the right femora of 27 Sprague-Dawley rats. The defects received a single, intralesional, percutaneous injection of 2.7 x 10(7) (low dose), 2.7 x 10(8) (medium dose), or 2.7 x 10(9) (high dose) plaque-forming units of Ad.BMP-2. After 8 weeks, femora were evaluated by X-ray, dual-energy X-ray absorptiometry, microcomputed tomography (microCT), and histology. The high dose of vector bridged 100%, the medium dose 11%, and the low dose 25% of the defects, as evaluated by X-ray and microCT imaging. Bone mineral content and bone volume of the defects receiving the high dose of vector were significantly higher than those of both groups receiving lower doses. Histologically, defects treated with the high dose were filled by trabecular bone and small amounts of cartilage, whereas large areas of fibrous tissue and cartilage remained in the defects receiving lower doses. However, the newly formed bone lacked the structural organization of native bone, suggesting that further maturation is necessary.


Gaze strategies for avoiding obstacles: Differences between young and elderly subjects.
Visual input is highly relevant for safely stepping over obstacles. In this study, gaze-behaviour was investigated in elderly, middle-aged and young subjects as they walked on a treadmill repeatedly stepping over obstacles, which approached either on the right or left side. In between obstacle-steps, subjects visually fixated a target N or F located two or four steps ahead on the floor, respectively. An acoustic warning signal announced the obstacles, after which subjects were free to look wherever they wanted. Gaze-movements were measured by video-oculography. Four conditions with 20 obstacles were conducted (two with target N, two with target F). In two conditions, high-precision stepping was investigated by asking subjects to step with minimal foot-clearance over the obstacles, while receiving acoustic feedback about their performance. In the high-precision conditions, more subjects (target N: 70%, F: 81%) turned their gaze on the obstacles and for a longer time than in unrestricted conditions. When fixating on the near target N and unrestricted stepping over the obstacles, significantly more elderly subjects (85%) turned their gaze on the obstacle compared to middle-aged (17%) and young subjects (29%). The elderly turned their gaze earlier and longer on the obstacle than middle-aged or young subjects. Our results reveal a different gaze-behaviour strategy of elderly subjects suggesting a greater dependency on visual inputs.


Computer-Based Training in Eating and Nutrition Facilitates Person-Centered Hospital Care: A Group Concept Mapping Study.
Studies have shown that computer-based training in eating and nutrition for hospital nursing staff increased the likelihood that patients at risk of undernutrition would receive nutritional interventions. This article seeks to provide understanding from the perspective of nursing staff of conceptually important areas for computer-based nutritional training, and their relative importance to nutritional care, following completion of the training. Group concept mapping, an integrated qualitative and quantitative methodology, was used to conceptualize important factors relating to the training experiences through four focus groups (n = 43), statement sorting (n = 38), and importance rating (n = 32), followed by multidimensional scaling and cluster analysis. Sorting of 38 statements yielded four clusters. These clusters (number of statements) were as follows: personal competence and development (10), practice close care development (10), patient safety (9), and awareness about the nutrition care process (9). First and second clusters represented "the learning organization," and third and fourth represented "quality improvement." These findings provide a conceptual basis for understanding the importance of training in eating and nutrition, which contributes to a learning organization and quality improvement, and can be linked to and facilitates person-centered nutritional care and patient safety.


Patients with faecal peritonitis admitted to European intensive care units: an epidemiological survey of the GenOSept cohort.
Faecal peritonitis (FP) is a common cause of sepsis and admission to the intensive care unit (ICU). The Genetics of Sepsis and Septic Shock in Europe (GenOSept) project is investigating the influence of genetic variation on the host response and outcomes in a large cohort of patients with sepsis admitted to ICUs across Europe. Here we report an epidemiological survey of the subset of patients with FP. To define the clinical characteristics, outcomes and risk factors for mortality in patients with FP admitted to ICUs across Europe. Data was extracted from electronic case report forms. Phenotypic data was recorded using a detailed, quality-assured clinical database. The primary outcome measure was 6-month mortality. Patients were followed for 6 months. Kaplan-Meier analysis was used to determine mortality rates. Cox proportional hazards regression analysis was employed to identify independent risk factors for mortality. Data for 977 FP patients admitted to 102 centres across 16 countries between 29 September 2005 and 5 January 2011 was extracted. The median age was 69.2 years (IQR 58.3-77.1), with a male preponderance (54.3%). The most common causes of FP were perforated diverticular disease (32.1%) and surgical anastomotic breakdown (31.1%). The ICU mortality rate at 28 days was 19.1%, increasing to 31.6% at 6 months. The cause of FP, pre-existing co-morbidities and time from estimated onset of symptoms to surgery did not impact on survival. The strongest independent risk factors associated with an increased rate of death at 6 months included age, higher APACHE II score, acute renal and cardiovascular dysfunction within 1 week of admission to ICU, hypothermia, lower haematocrit and bradycardia on day 1 of ICU stay. In this large cohort of patients admitted to European ICUs with FP the 6 month mortality was 31.6%. The most consistent predictors of mortality across all time points were increased age, development of acute renal dysfunction during the first week of admission, lower haematocrit and hypothermia on day 1 of ICU admission.


Association of Anemia with Outcomes of Acute Heart Failure.
Anemia is common in patients presenting with acute congestive heart failure (CHF); when hemoglobin (HGB) declines to low levels, it can result in worse outcomes. The aim of this study was to determine a level of HGB on admission or discharge that affects outcomes in patients with CHF and then to evaluate the effect of the low HGB levels on these outcomes. We conducted a retrospective cohort study of 756 patients admitted with acute CHF during the period January 1, 2011-December 31, 2014. We used multivariable regression analysis to evaluate the relation among HGB levels and three major outcomes: 3-year mortality, 30-day readmission rate, and length of stay (LOS). Compared with patients with HGB ≥10 g/dL, patients with HGB <10 g/dL on discharge from the hospital had higher mortality (3-year survival 46% vs 33%, P = 0.023) and 30-day readmission rates (23% vs 14%; P = 0.008) and increased LOS (4.8 vs 3.2 days, P < 0.001). Patients with admission HGB <10 g/dL had higher mortality rates (3-year survival 45% vs 32%, P = 0.019) and increased LOS (4.5 vs 3.4 days, P = 0.014). A lower admission HGB value was associated with higher 30-day readmission rates, but it was not statistically significant (P = 0.06). An HGB level <10 g/dL on admission or discharge in patients hospitalized with acute CHF is associated with a significantly worse outcome.


Use of nonsteroidal antiinflammatory drugs: is there a change in patient risk profile after withdrawal of rofecoxib?
Use of traditional nonsteroidal antiinflammatory drugs (tNSAID) increased after rofecoxib withdrawal. tNSAID use is associated with increased gastrointestinal (GI) toxicity and cardiovascular (CV) risk similar to celecoxib. The objective of our study was to describe changes in celecoxib and tNSAID use regarding GI and CV risk and congestive heart failure (CHF) and renal risk that occurred in Quebec, Canada, between April 2005-March 2007 (the post-period) compared to April 2002-March 2004 (the pre-period). Data were obtained from the provincial health insurance agency. All NSAID users ≥ 50 years of age were considered. Celecoxib use decreased by 23% (coxib 61%) while that of tNSAID doubled. In both periods, celecoxib users were older and included more women, and they suffered more frequently from arthritis. Users of celecoxib were more likely to have higher level of GI risk: post-period odds ratios compared to low GI risk, very high 1.79 (95% CI 1.63, 1.97), high 1.76 (95% CI 1.71, 1.81), and moderate 1.30 (95% CI 1.27, 1.33); similar results were observed in the pre-period. Celecoxib users had higher CV risk levels in the pre-period: OR compared to low CV risk, very high 1.13 (95% CI 1.08, 1.19), high 1.24 (95% CI 1.20, 1.29), and moderate 1.16 (95% CI 1.14, 1.19); and in the post-period, very high 0.85 (95% CI 0.81, 0.89), high 1.13 (95% CI 1.10, 1.16), and moderate 1.15 (95% CI 1.12, 1.17). CHF and renal risk factors did not play an important role in the choice of NSAID in either period. Current NSAID use differs from that prior to 2004. Coxib utilization decreased substantially and patients at high CV risk seem less likely to receive celecoxib, while those at high GI risk seem more likely to receive it.


Civilian Prehospital Tourniquet Use Is Associated with Improved Survival in Patients with Peripheral Vascular Injury.
Tourniquet use has been proven to reduce mortality on the battlefield. Although empirically transitioned to the civilian environment, data substantiating survival benefit attributable to civilian tourniquet use is lacking. We hypothesized that civilian prehospital tourniquet use is associated with reduced mortality in patients with peripheral vascular injuries. We conducted a multicenter retrospective review of all patients sustaining peripheral vascular injuries admitted to 11 Level I trauma centers (January 2011 through December 2016). The study population was divided into 2 groups based on prehospital tourniquet use. Baseline characteristics were compared and factors associated with mortality identified. Logistic regression, adjusting for demographic, physiologic and injury-related parameters, was used to evaluate the association between prehospital tourniquet use and mortality. Delayed amputation was the secondary end point. During 6 years, 1,026 patients with peripheral vascular injuries were admitted. Prehospital tourniquets were used in 181 (17.6%) patients. Tourniquet time averaged 77.3 ± 63.3 minutes (interquartile range 39.0 to 92.3 minutes). Traumatic amputations occurred in 98 patients (35.7% had a tourniquet). Mortality was 5.2% in the non-tourniquet group compared with 3.9% in the tourniquet group (odds ratio 1.36; 95% CI 0.60 to 1.65; p = 0.452). After multivariable analysis, the use of tourniquets was found to be independently associated with survival (adjusted odds ratio 5.86; 95% CI 1.41 to 24.47; adjusted p = 0.015). Delayed amputation rates were not significantly different between the 2 groups (1.1% vs 1.1%; adjusted odds ratio 1.82; 95% CI 0.36 to 9.99; adjusted p = 0.473). Although still underused, civilian prehospital tourniquet application was independently associated with a 6-fold mortality reduction in patients with peripheral vascular injuries. More aggressive prehospital application of extremity tourniquets in civilian trauma patients with extremity hemorrhage and traumatic amputation is warranted.


Membrane topology of the xenobiotic-exporting subunit, MexB, of the MexA,B-OprM extrusion pump in Pseudomonas aeruginosa.
The MexA,B-OprM efflux pump assembly of Pseudomonas aeruginosa consists of two inner membrane proteins and one outer membrane protein. The cytoplasmic membrane protein, MexB, appears to function as the xenobiotic-exporting subunit, whereas the MexA and OprM proteins are supposed to function as the membrane fusion protein and the outer membrane channel protein, respectively. Computer-aided hydropathy analyses of MexB predicted the presence of up to 17 potential transmembrane segments. To verify the prediction, we analyzed the membrane topology of MexB using the alkaline phosphatase gene fusion method. We obtained the following unique characteristics. MexB bears 12 membrane spanning segments leaving both the amino and carboxyl termini in the cytoplasmic side of the inner membrane. Both the first and fourth periplasmic loops had very long hydrophilic domains containing 311 and 314 amino acid residues, respectively. This fact suggests that these loops may interact with other pump subunits, such as the membrane fusion protein MexA and the outer membrane protein OprM. Alignment of the amino- and the carboxyl-terminal halves of MexB showed a 30% homology and transmembrane segments 1, 2, 3, 4, 5, and 6 could be overlaid with the segments 7, 8, 9, 10, 11, and 12, respectively. This result suggested that the MexB has a 2-fold repeat that strengthen the experimentally determined topology model. This paper reports the structure of the pump subunit, MexB, of the MexA,B-OprM efflux pump assembly. This is the first time to verify the topology of the resistant-nodulation-division efflux pump protein.


Contextual cues and the retrieval of information from cognitive maps.
In three experiments, we investigated how retrieval cues affect memory for cognitive maps. Participants first rated a list of landmarks either for the importance of the activity performed or for the frequency of visitation at each landmark (Experiments 1 and 2), or on both dimensions (Experiment 3). Landmarks ranked high and low on these dimensions were selected and served as the bases for distance estimations and route descriptions. Distances estimated using importance as a criterion for selection were significantly longer than those using frequency of visitation as a criterion. Participants in the importance group also produced more route perspective expressions than survey expressions in their descriptions, whereas participants in the frequency group did not differ in the relative use of these types of perspective expressions (Experiment 1). These findings suggest that deviations in distance estimation and the use of perspectives in route description are a result of contextual manipulation and the procedures invoked during judgments.


A cross-sectional study of individuals seeking information on transient ischemic attack and stroke symptoms online: a target for intervention?
Individuals with TIA/stroke symptoms often do not seek urgent medical attention. We assessed the feasibility of identifying individuals searching for information on TIA/stroke symptoms online as a target for future interventions to encourage urgent evaluation and we evaluated the performance of a self-reported risk score to identify subjects with true TIA or stroke. We placed online advertisements to target English-speaking adults in the United States searching for TIA/stroke-related keywords. After completing an online questionnaire, participants were telephoned by a vascular neurologist to assess the likelihood of TIA/stroke. We used logistic regression and the c-statistic to assess associations and model discrimination respectively. Over 122 days, 251 (1%) of 25,292 website visitors completed the online questionnaire and 175 were reached by telephone (mean age 58.5 years; 63% women) for follow-up. Of these participants, 37 (21%) had symptoms within 24 hours, 60 (34%) had not had a medical evaluation yet, and 68 (39%) had TIA/stroke. Applying a modified ABCD(2) score yielded a c-statistic of 0.66, but 2 of 12 with a zero score had a TIA/stroke. Those with new symptoms were more likely to have TIA/stroke (OR 4.90, 95% CI 2.56-9.09). Individuals with TIA/stroke that are seeking real-time information on symptoms online can be readily identified, in some cases before they have sought formal medical evaluation. Although a simple self-reported risk score was unable to identify a low-risk population in this selected group, this population may still present an attractive target for future interventions designed to encourage urgent medical evaluation.


Assistive locomotion device with haptic feedback for guiding visually impaired people.
Robotic assistive devices are able to enhance physical stability and balance. Smart walkers, in particular, are also capable of offering cognitive support for individuals whom conventional walkers are unsuitable. However, visually impaired individuals often need additional sensorial assistance from those devices. This work proposes a smart walker with an admittance controller for guiding visually impaired individuals along a desired path. The controller uses as inputs the physical interaction between the user and the walker to provide haptic feedback hinting the path to be followed. Such controller is validated in a set of experiments with healthy individuals. At first, users were blindfolded during navigation to assess the capacity of the smart walker in providing guidance without visual input. Then, the blindfold is removed and the focus is on evaluating the human-robot interaction when the user had visual information during navigation. The results indicate that the admittance controller design and the design of the guidance path were factors impacting on the level of comfort reported by users. In addition, when the user was blindfolded, the linear velocity assumed lower values than when did not wear it, from a mean value of 0.19 m/s to 0.21 m/s.


High density lipoprotein cholesterol and proteome in SR-B1 KO mice: lost in precipitation.
Scavenger receptor class B type 1 (SR-B1) plays an essential role in high density lipoprotein (HDL) metabolism. SR-B1 deficient (SR-B1 KO) mice are prone to atherosclerosis and exhibit abnormally large, cholesterol-rich, dysfunctional HDL. In a recent issue of J Transl Med, Cao et al. described results of proteomics analyses of HDL isolated from wild-type (WT) and SR-B1 KO mice using precipitation of large lipoproteins with polyethylene glycol (PEG). They report abnormalities in SR-B1 KO HDL protein components that correlate with HDL function. In this commentary, we describe and discuss the differences in the results published by Cao et al. and those obtained in a recent study from our laboratory using shotgun proteomics of HDL of SR-B1 KO mice isolated by ultracentrifugation. We propose that different HDL purification procedures used may account for the discrepancies observed. We show that SR-B1 KO HDL purification using either PEG or dextran sulfate precipitation results in enrichment of small HDL subclasses, and may therefore underestimate alterations in lipoprotein composition or function. Compared to HDL obtained by ultracentrifugation, HDL isolated by PEG precipitation show a lower ApoE/ApoA-I proportion and reduced cholesterol content. HDL protein components described by Cao et al. or our laboratory are mostly inconsistent: only 33 HDL proteins were detected in both datasets, whereas a significant number of proteins were only identified by Cao et al. (n = 43) or Contreras-Duarte et al. (n = 26) datasets. The relative abundance of HDL-associated peptide and protein levels in WT vs SR-B1 HDL were also highly different in both datasets. This study indicates that caution must be taken when interpreting results from HDL isolated by chemical precipitation.


Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.
The fruit fly Drosophila melanogaster (Dm) mutant for PTEN-induced putative kinase 1 (PINK1B9) gene is a powerful tool to investigate physiopathology of Parkinson's disease (PD). Using PINK1B9 mutant Dm we sought to explore the effects of Mucuna pruriens methanolic extract (Mpe), a L-Dopa-containing herbal remedy of PD. The effects of Mpe on PINK1B9 mutants, supplied with standard diet to larvae and adults, were assayed on 3-6 (I), 10-15 (II) and 20-25 (III) days old flies. Mpe 0.1% significantly extended lifespan of PINK1B9 and fully rescued olfactory response to 1-hexanol and improved climbing behavior of PINK1B9 of all ages; in contrast, L-Dopa (0.01%, percentage at which it is present in Mpe 0.1%) ameliorated climbing of only PINK1B9 flies of age step II. Transmission electron microscopy analysis of antennal lobes and thoracic ganglia of PINK1B9 revealed that Mpe restored to wild type (WT) levels both T-bars and damaged mitochondria. Western blot analysis of whole brain showed that Mpe, but not L-Dopa on its own, restored bruchpilot (BRP) and tyrosine hydroxylase (TH) expression to age-matched WT control levels. These results highlight multiple sites of action of Mpe, suggesting that its effects cannot only depend upon its L-Dopa content and support the clinical observation of Mpe as an effective medication with intrinsic ability of delaying the onset of chronic L-Dopa-induced long-term motor complications. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the properties of Mucuna pruriens for PD treatment.


A proposal for standardization in forensic canine DNA typing: allele nomenclature of six canine-specific STR loci.
In this study a proposal for the allele nomenclature of six polymorphic short tandem repeat (STR) loci (PEZ3, PEZ6, PEZ8, PEZ10, FHC2161, and FHC2328) for canine genotyping (Canis lupus familiaris) is presented. The nomenclature is based on the sequence data of the polymorphic region of the microsatellite markers as recommended by the DNA commission of the International Society of Forensic Haemogenetics (ISFH) in 1994 for human DNA typing. To cover commonly and rarely occurring alleles, a selection of homozygous and heterozygous animals were analyzed and subjected to sequence studies. The alleles consisted of simple tri- and tetra-nucleotide repeat patterns as well as compound and highly complex repeat patterns. Several alleles revealing the same fragment size but different repeat structures were found. The allele designation described here was adopted to the number of repeats, including all variable regions within the amplified fragment. In a second step the most commonly occurring alleles were added to an allelic ladder for each marker allowing a reliable typing of all alleles differing in size. A total number of 142 unrelated dogs from surrounding municipal animal homes, private households, and canines in police duty were analyzed. The data were added to a population database providing allele frequencies for each marker.


Accelerated forgetting of real-life events in Transient Epileptic Amnesia.
Transient Epileptic Amnesia (TEA) is a form of temporal lobe epilepsy associated with ictal and interictal memory disturbance. Some patients with TEA exhibit Accelerated Long-term Forgetting (ALF), in which memory for verbal and non-verbal material is retained normally over short delays but fades at an unusually rapid rate over days to weeks. This study addresses three questions about ALF in TEA: (i) whether real-life events undergo ALF in a similar fashion to laboratory-based stimuli; (ii) whether ALF can be detected within 24h; (iii) whether procedural memories are susceptible to ALF. Eleven patients with TEA and eleven matched healthy controls wore a novel, automatic camera, SenseCam, while visiting a local attraction. Memory for images of events was assessed on the same day and after delays of one day, one week, and three weeks. Forgetting of real-life events was compared with forgetting of a word list and with performance on a procedural memory task. On the day of their excursion, patients and controls recalled similar numbers of primary events, associated secondary details (contiguous events, thoughts and sensory information) and items from the word list. In contrast, patients showed ALF for primary events over three weeks, with ALF for contiguous events, thoughts and words over the first day. Retention on the procedural memory task was normal over three weeks. The results indicate that accelerated forgetting in TEA: (i) affects memory for real-life events as well as laboratory stimuli; (ii) is maximal over the first day; and (iii) is specific to declarative memories.


Influence of irrigated paddy fields on the fluorescence properties of fluvial dissolved organic matter.
This study investigated seasonal and geographical variation in the fluorescence properties of dissolved organic matter (DOM) in a river system that includes rice paddy fields in its watershed. The river system covers a northern area of the main island of Japan, and between 6 and 45% the watershed area of the tributaries is paddy fields. Water samples were collected monthly from eight tributaries for 1 yr, and the fluorescence properties of DOM were monitored by combined excitation-emission matrix (EEM) and parallel factor analysis. The EEM was statistically decomposed into six fluorescence components with different environmental dynamics. The relative proportion of these components varied with season and geographic location, the former having a greater effect than the latter. Seasonal variation is largely attributed to changes in the source of DOM associated with irrigated rice cultivation practice. The fluorescence component composition showed a stronger autochthonous signature, which varied over a wider range during off-cropping period (October-April) than cropping period (May-September). During the cropping period, a large amount of allochthonous DOM with relatively similar quality was transported into river water from flooded paddy fields and masked the variability in the quality of DOM among tributaries. Therefore, irrigated rice cropping practices are considered to be one of major factors that influence seasonal and geographical variation of fluvial DOM composition.


Gene promoter of apoptosis inhibitory protein IAP2: identification of enhancer elements and activation by severe hypoxia.
Inhibitors of apoptosis (IAPs) antagonize cell death and regulate the cell cycle. One mechanism controlling IAP expression is translation initiation through the internal ribosome entry sites. Alternatively, IAP expression can be regulated at the transcription level. We showed recently the activation of IAP2 transcription by severe hypoxia. To pursue this regulation, we have cloned the full-length cDNA of rat IAP2, and have isolated and analysed the promoter regions of this gene. The cDNA encodes a protein of 589 amino acids, exhibiting structural features of IAP. In rat tissues, a major IAP2 transcript of approximately 3.5 kb was detected. We subsequently isolated 3.3 kb of the proximal 5'-flanking regions of this gene, which showed significant promoter activity. Of interest, 5' sequential deletion of the promoter sequence identified an enhancer of approximately 200 bp. Deletion of cAMP-response-element-binding protein (CREB) sites in the enhancer sequence diminished its activity. Finally, the IAP2 gene promoter was activated significantly by severe hypoxia and not by CoCl(2) or desferrioxamine, pharmacological inducers of hypoxia-inducible factor-1. In conclusion, in this study we have cloned the full-length cDNA of rat IAP2, and for the first time we have isolated and analysed promoter sequences of this gene, leading to the identification of enhancer elements. Moreover, we have demonstrated activation of the gene promoter by severe hypoxia, a condition shown to induce IAP2. These findings provide a basis for further investigation of gene regulation of IAP2, a protein with multiple functions.


Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1.
We investigated the role of glycogen synthase kinase-3 (GSK-3), which is inactivated by AKT, for its role in the regulation of apoptosis. Upon IL-3 withdrawal, protein levels of MCL-1 decreased but were sustained by pharmacological inhibition of GSK-3, which prevented cytochrome c release and apoptosis. MCL-1 was phosphorylated by GSK-3 at a conserved GSK-3 phosphorylation site (S159). S159 phosphorylation of MCL-1 was induced by IL-3 withdrawal or PI3K inhibition and prevented by AKT or inhibition of GSK-3, and it led to increased ubiquitinylation and degradation of MCL-1. A phosphorylation-site mutant (MCL-1(S159A)), expressed in IL-3-dependent cells, showed enhanced stability upon IL-3 withdrawal and conferred increased protection from apoptosis compared to wild-type MCL-1. The results demonstrate that the control of MCL-1 stability by GSK-3 is an important mechanism for the regulation of apoptosis by growth factors, PI3K, and AKT.


Downregulation of thymidylate synthase and E2F1 by arsenic trioxide in mesothelioma.
Malignant pleural mesothelioma is a global health issue. Arsenic trioxide (ATO) has been shown to suppress thymidylate synthase (TYMS) in lung adenocarcinoma and colorectal cancer, and induce apoptosis in acute promyelocytic leukemia. With TYMS as a putative therapeutic target, the effect of ATO in mesothelioma was therefore studied. A panel of 5 mesothelioma cell lines was used to study the effect of ATO on cell viability, protein expression, mRNA expression and TYMS activity by MTT assay, western blot, qPCR and tritium-release assay, respectively. The knockdown of TYMS and E2F1 was performed with a specific siRNA. Phosphatidylserine externalization and mitochondrial membrane depolarization were measured by Annexin V and JC-1 staining respectively. The in vivo effect of ATO was studied using a nude mouse xenograft model. Application of ATO demonstrated anticancer effects in the cell line model with clinically achievable concentrations. Downregulation of TYMS protein (except H226 cells and 1.25 µM ATO in H2052 cells) and mRNA expression (H28 cells), pRB1 (H28 cells) and E2F1 and TYMS activity (except H226 cells) were also evident. E2F1 knockdown decreased cell viability more significantly than TYMS knockdown. In general, thymidine kinase 1, ribonucleotide reductase M1, c-myc and skp2 were downregulated by ATO. p-c-Jun was downregulated in H28 cells while upregulated in 211H cells. Phosphatidylserine externalization, mitochondrial membrane depolarization, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bak and cleaved caspase-3 were observed. In the H226 xenograft model, the relative tumor growth was aborted, and E2F1 was downregulated while cleaved caspase-3 was elevated and localized to the nucleus in the ATO treatment group. ATO has potent antiproliferative and cytotoxic effects in mesothelioma in vitro and in vivo, partially mediated through E2F1 targeting (less effect through TYMS targeting). There is sound scientific evidence to support the clinical application of ATO in treatment of mesothelioma.


Income and Physical Activity among Adults: Evidence from Self-Reported and Pedometer-Based Physical Activity Measurements.
This study examined the relationship between income and physical activity by using three measures to illustrate daily physical activity: the self-reported physical activity index for leisure-time physical activity, pedometer-based total steps for overall daily physical activity, and pedometer-based aerobic steps that reflect continuous steps for more than 10 min at a time. The study population consisted of 753 adults from Finland (mean age 41.7 years; 64% women) who participated in 2011 in the follow-up of the ongoing Young Finns study. Ordinary least squares models were used to evaluate the associations between income and physical activity. The consistency of the results was explored by using register-based income information from Statistics Finland, employing the instrumental variable approach, and dividing the pedometer-based physical activity according to weekdays and weekend days. The results indicated that higher income was associated with higher self-reported physical activity for both genders. The results were robust to the inclusion of the control variables and the use of register-based income information. However, the pedometer-based results were gender-specific and depended on the measurement day (weekday vs. weekend day). In more detail, the association was positive for women and negative or non-existing for men. According to the measurement day, among women, income was positively associated with aerobic steps despite the measurement day and with totals steps measured on the weekend. Among men, income was negatively associated with aerobic steps measured on weekdays. The results indicate that there is an association between income and physical activity, but the association is gender-specific and depends on the measurement type of physical activity.


Willingness to Participate in Research during Pregnancy: Race, Experience, and Motivation.
This paper examines the willingness of pregnant women to participate in research on health. We investigate attitudes toward multiple methods of data collection including survey and biomarker data collection. Complete interviews were obtained from a sample of 90 pregnant women in a matched control-comparison study of patients receiving prenatal care in private practice and clinic settings. Women experiencing prenatal care at a clinic reported less willingness to participate in research than women experiencing prenatal care at a private practice. Women who deemed "contributing to science", "learning about pregnancy health", and "helping future patients" as important motivations for participating in research were more likely to express willingness to participate in a study. African American women reported less willingness to answer questions in a survey compared to white women. The results suggest that motivational factors should be integrated into the design of a study of pregnant women to encourage participation.


Anatomic and functional abnormalities of the esophagus in infants surviving congenital diaphragmatic hernia.
As more infants with congenital diaphragmatic hernia (CDH) survive by means of extracorporeal membrane oxygenation (ECMO), new clinical observations are being made. We report anatomic and functional abnormalities of the esophagus in these infants. Twenty-two of 30 infants with CDH survived. Three of 7 non-ECMO-treated infants and 14 of 17 ECMO-treated infants had an air- or fluid-filled mediastinal mass that was confirmed by an upper gastrointestinal series as ectatic esophagus. Contrast studies demonstrated severe gastroesophageal reflux. Intra-esophageal pH monitoring confirmed significant reflux (Euler scores greater than 50) in 69% of tested patients. Prolonged acid clearance in most patients implied abnormal peristalsis. Hydramnios was correlated to the observed esophageal abnormalities, being present in 13 of 16 infants with an available amniotic history. All patients had symptomatic gastroesophageal reflux managed without antireflux surgery and were discharged 36 +/- 2 days after initiation of feeding. Follow-up (range: 7 to 56 months; mean: 32 months) showed that weight gain in affected children was slower than in those not affected. All but one are asymptomatic. Repeat upper gastrointestinal series shows persistent ectasia but less gastro-esophageal reflux. Gastroesophageal reflux/ectasia is a new observation with CDH. The associated hydramnios may result from proximal foregut obstruction by kinking the gastroesophageal junction with CDH. The radiographic appearance can be quite unusual. Clinical manifestations of gastro-esophageal reflux are manageable without surgery but may account for the observed compromised growth.


Development of antibodies to human thrombin and factor V in a pediatric patient exposed to topical bovine thrombin.
Bovine topical thrombin is commonly used for local hemostasis in pediatric surgery. Acquired inhibitors to coagulation factors, particularly to factor V and bovine thrombin, have been infrequently reported in the pediatric population. We report a 3-year-old male who developed a coagulopathy and clinical bleeding after cardiothoracic surgery, during which bovine topical thrombin was used for local hemostasis. Laboratory tests revealed elevated prothrombin, partial thromboplastin, and thrombin times, and a low factor V activity level. He was found to have both human-thrombin and factor V inhibitors, among the first reported cases of these combined inhibitors secondary to bovine topical thrombin. He was treated with intravenous immunoglobulin and steroids with a rapid and durable response.


A human immune system mouse model with robust lymph node development.
Lymph nodes (LNs) facilitate the cellular interactions that orchestrate immune responses. Human immune system (HIS) mice are powerful tools for interrogation of human immunity but lack secondary lymphoid tissue (SLT) as a result of a deficiency in Il2rg-dependent lymphoid tissue inducer cells. To restore LN development, we induced expression of thymic-stromal-cell-derived lymphopoietin (TSLP) in a Balb/c Rag2-/-Il2rg-/-SirpaNOD (BRGS) HIS mouse model. The resulting BRGST HIS mice developed a full array of LNs with compartmentalized human B and T cells. Compared with BRGS HIS mice, BRGST HIS mice have a larger thymus, more mature B cells, and abundant IL-21-producing follicular helper T (TFH) cells, and show enhanced antigen-specific responses. Using BRGST HIS mice, we demonstrated that LN TFH cells are targets of acute HIV infection and represent a reservoir for latent HIV. In summary, BRGST HIS mice reflect the effects of SLT development on human immune responses and provide a model for visualization and interrogation of regulators of immunity.


Aggressive fibromatosis (desmoid tumor) is a monoclonal disorder.
Aggressive fibromatosis (also called deep fibromatosis or desmoid tumor) is a proliferation of cytologically benign-appearing fibrocytes, often resulting in significant functional loss. The nature of the lesion is controversial: some evidence suggests that it is a reactive process, whereas other evidence supports a neoplastic etiology. The pattern of X chromosome inactivation, using a technique based on polymerase chain reaction (PCR) amplification of a hypervariable CAG repeat region flanking Hhal restriction sites of the human androgen receptor gene, was determined in four cases in which cryopreserved tumor and adjacent normal tissue were available. All four tumors demonstrated a monoclonal pattern, while the adjacent normal tissues demonstrated a polyclonal pattern. This demonstrates that aggressive fibromatosis is proliferation of cells derived from a single clone with a growth advantage, and thus is likely a neoplastic process.


Rac1 is deactivated at integrin activation sites through an IQGAP1-filamin-A-RacGAP1 pathway.
Cell migration makes a fundamental contribution to both normal physiology and disease pathogenesis. Integrin engagement with extracellular ligands spatially controls, via the cyclical activation and deactivation of the small GTPase Rac1, the dynamic membrane protrusion and cytoskeletal reorganization events that are required for directional migration. Although the pathways that control integrin-mediated Rac1 activation are reasonably well defined, the mechanisms that are responsible for switching off activity are poorly understood. Here, proteomic analysis of activated integrin-associated complexes suggests filamin-A and IQ-motif-containing GTPase-activating protein 1 (IQGAP1) as candidates that link β1 integrin to Rac1. siRNA-mediated knockdown of either filamin-A or IQGAP1 induced high, dysregulated Rac1 activity during cell spreading on fibronectin. Using immunoprecipitation and immunocytochemistry, filamin-A and IQGAP1 were shown to be part of a complex that is recruited to active β1 integrin. Mass spectrometric analysis of individual filamin-A, IQGAP1 and Rac1 pull-downs and biochemical analysis, identified RacGAP1 as a novel IQGAP1 binding partner. Further immunoprecipitation and immunocytochemistry analyses demonstrated that RacGAP1 is recruited to IQGAP1 and active β1 integrin, and that suppression of RacGAP1 expression triggered elevated Rac1 activity during spreading on fibronectin. Consistent with these findings, reduced expression of filamin-A, IQGAP1 or RacGAP1 triggered unconstrained membrane protrusion and disrupted directional cell migration on fibrillar extracellular matrices. These findings suggest a model whereby integrin engagement, followed by filamin-A, IQGAP1 and RacGAP1 recruitment, deactivates Rac1 to constrain its activity spatially and thereby coordinate directional cell migration.


Rates and modes of body size evolution in early carnivores and herbivores: a case study from Captorhinidae.
Body size is an extremely important characteristic, impacting on a variety of ecological and life-history traits. It is therefore important to understand the factors which may affect its evolution, and diet has attracted much interest in this context. A recent study which examined the evolution of the earliest terrestrial herbivores in the Late Carboniferous and Early Permian concluded that in the four herbivorous clades examined there was a trend towards increased body size, and that this increase was more substantial than that observed in closely related carnivorous clades. However, this hypothesis was not based on quantitative examination, and phylogenetic comparative methods provide a more robust means of testing such hypotheses. Here, the evolution of body size within different dietary regimes is examined in Captorhinidae, the most diverse and longest lived of these earliest high fibre herbivores. Evolutionary models were fit to their phylogeny to test for variation in rate and mode of evolution between the carnivorous and herbivorous members of this clade, and an analysis of rate variation throughout the tree was carried out. Estimates of ancestral body sizes were calculated in order to compare the rates and direction of evolution of lineages with different dietary regimes. Support for the idea that the high fibre herbivores within captorhinids are being drawn to a higher adaptive peak in body size than the carnivorous members of this clade is weak. A shift in rates of body size evolution is identified, but this does not coincide with the evolution of high-fibre herbivory, instead occurring earlier in time and at a more basal node. Herbivorous lineages which show an increase in size are not found to evolve at a faster rate than those which show a decrease; in fact, it is those which experience a size decrease which evolve at higher rates. It is possible the shift in rates of evolution is related to the improved food processing ability of the more derived captorhinids rather than a shift in diet, but the evidence for this is circumstantial.


Organometallic and radical intermediates reveal mechanism of diphthamide biosynthesis.
Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed by a radical S-adenosylmethionine (SAM) enzyme that cleaves a carbon-sulfur (C-S) bond in SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. Using rapid freezing, we have captured an organometallic intermediate with an iron-carbon (Fe-C) bond between ACP and the enzyme's [4Fe-4S] cluster. In the presence of the substrate protein, elongation factor 2, this intermediate converts to an organic radical, formed by addition of the ACP radical to a histidine side chain. Crystal structures of archaeal diphthamide biosynthetic radical SAM enzymes reveal that the carbon of the SAM C-S bond being cleaved is positioned near the unique cluster Fe, able to react with the cluster. Our results explain how selective C-S bond cleavage is achieved in this radical SAM enzyme.


Inequalities in uptake of influenza vaccine by deprivation and risk group: time trends analysis.
The aim of this study was to investigate influenza immunisation rates in the United Kingdom over a 6-year period and examine trends in uptake by deprivation, ethnicity, rurality and risk group. Influenza immunisation rates were determined from 1999/2000 to 2004/2005 using a large general practice database (QRESEARCH). There was a relative increase of 59.5% in the overall influenza vaccination rate over the study period. In 2004/2005, 70.2% of all patients aged 65 and over were vaccinated, compared with 29.3% of patients in a clinical risk group aged less than 65. Males, patients from deprived areas and from areas with a higher proportion of non-White residents had slightly lower vaccination rates overall. This general practice based study suggests that substantial increases in influenza vaccination rates have occurred across all risk groups, but that increased focus should be given to immunising high-risk patients below the age of 65.


Local governments' dependence on tobacco tax revenue: a deterrent to tobacco control in the Republic of Korea.
To investigate, in the Republic of Korea, whether local governments' participation in an anti-smoking programme supported by the National Health Promotion Fund in 2002-2003 was related to the percentage of local tax revenue comprised by the tobacco consumption tax (TCT). Using financial and administrative data on 163 municipalities, the authors estimated logit models of local governments' participation in the anti-smoking programme as a function of the proportion of local tax revenue that came from the TCT and a set of control variables, namely local socioeconomic characteristics and the size of the staff in the local public health centre (PHC). Local governments that derived a greater percentage of their local tax revenue from the TCT, particularly those that ranked in the upper fourth in terms of this percentage, were less likely to participate in the anti-smoking programme. Insufficient staff in the PHC was also found to be associated with lower participation in the anti-smoking programme. Local governments' dependence on revenue from the TCT may be a deterrent to tobacco control in the Republic of Korea.


Transcranial direct current stimulation (tDCS) enhances reconsolidation of long-term memory.
A new and weak memory trace undergoes consolidation to gain resistance against interfering stimuli. When an encoded memory is recalled, it becomes labile and another round of consolidation, or reconsolidation, is required to restore its stability. Transcranial direct current stimulation (tDCS) is a non-invasive method of altering cortical excitability. The aim of this study was to examine the effects of tDCS on the reconsolidation of long-term verbal memory. Participants (n = 15) memorized words in the encoding session, then reactivated the memory of the words 3 h later using an old-new recognition task under anodal, cathodal and sham stimulation to the left dorsolateral prefrontal cortex (DLPFC). Finally, after another 5 h, they performed another round of the old-new recognition task and rated their confidence. Anodal tDCS during the second session resulted in significantly more words recognized in the third session as compared to cathodal and sham stimulation. Cathodal tDCS did not affect the recognition performance compared to sham stimulation. These results cannot be attributed to differences in response times and confidence ratings, as they were comparable in all conditions. In order to study whether the activation of a memory was crucial for the enhancing effects of anodal tDCS, a group of controls (n = 15) did not perform the recognition task in the second session but still underwent stimulation. Contrary to the main group, anodal stimulation did not enhance the memory performance for the control group. This result suggests that anodal tDCS over the left DLPFC can enhance the reconsolidation of long-term memory only when the memory has been reactivated.


Impact of youth sports specialisation on career and task-specific athletic performance: a systematic review following the American Medical Society for Sports Medicine (AMSSM) Collaborative Research Network's 2019 Youth Early Sport Specialisation Summit.
The impact, positive or negative, of youth sport specialisation (YSS) on short-term and long-term performance is not fully understood; however, the desire to maximise performance goals is generally considered the primary reason children and adolescents specialise at a young age. We performed a systematic review of original research to establish the association of YSS and task-focused or career-focused performance outcomes. Systematic review. Databases searched include PubMed, EMBASE, Cochrane, CINAHL and SPORTDiscus. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify peer-reviewed research articles published in English between 1 January 1990 and 31 December 2018 that reported original findings on the association of YSS and performance outcomes. Studies without an explicit measure of sport specialisation, for example, volume measures without measuring sport specialisation, were excluded. Twenty-two articles were included in the final review; 15 addressed career performance outcomes and 7 considered task performance outcomes. All identified studies were cross-sectional or retrospective in design. The proportion of elite athletes who specialised early ranged between 7% and 85%, depending on sport and definition of specialisation. Elite athletes often specialised between the ages of 14 and 15 compared with their non-elite or semi-elite peers who typically specialised prior to 13 years. In addition, neuromuscular control, anterior reach asymmetry and physical task outcomes did not differ by specialisation status. The volume and methodological rigour of published research in this field are limited. Our review suggests that YSS is not required to achieve success at elite levels. YSS also does not appear to improve task-related performance (eg, anterior reach, neuromuscular control) outcomes for specialised athletes when compared with non-specialised athletes during childhood and adolescence.


Geospatial analysis of emergency department visits for targeting community-based responses to the opioid epidemic.
The opioid epidemic in the United States carries significant morbidity and mortality and requires a coordinated response among emergency providers, outpatient providers, public health departments, and communities. Anecdotally, providers across the spectrum of care at Massachusetts General Hospital (MGH) in Boston, MA have noticed that Charlestown, a community in northeast Boston, has been particularly impacted by the opioid epidemic and needs both emergency and longer-term resources. We hypothesized that geospatial analysis of the home addresses of patients presenting to the MGH emergency department (ED) with opioid-related emergencies might identify "hot spots" of opioid-related healthcare needs within Charlestown that could then be targeted for further investigation and resource deployment. Here, we present a geospatial analysis at the United States census tract level of the home addresses of all patients who presented to the MGH ED for opioid-related emergency visits between 7/1/2012 and 6/30/2015, including 191 visits from 100 addresses in Charlestown, MA. Among the six census tracts that comprise Charlestown, we find a 9.5-fold difference in opioid-related ED visits, with 45% of all opioid-related visits from Charlestown originating in tract 040401. The signal from this census tract remains strong after adjusting for population differences between census tracts, and while this tract is one of the higher utilizing census tracts in Charlestown of the MGH ED for all cause visits, it also has a 2.9-fold higher rate of opioid-related visits than the remainder of Charlestown. Identifying this hot spot of opioid-related emergency needs within Charlestown may help re-distribute existing resources efficiently, empower community and ED-based physicians to advocate for their patients, and serve as a catalyst for partnerships between MGH and local community groups. More broadly, this analysis demonstrates that EDs can use geospatial analysis to address the emergency and longer-term health needs of the communities they are designed to serve.


Strain rate dependent nanostructure of hydrogels with reversible hydrophobic associations during uniaxial extension.
An energy dissipation mechanism during deformation is required to impart toughness to hydrogels. Here we describe how in situ small angle X-ray scattering (SAXS) provides insight into possible energy dissipation mechanisms for a tough hydrogel based on an amphiphilic copolymer where nanoscale associations of the hydrophobic moieties act as effective crosslinks. The mechanical properties of the hydrogels are intimately coupled with the nanostructure that provides reversible crosslinks and evolves during deformation. As the extension rate increases, more mechanical energy is dissipated from rearrangements of the crosslinks. The scattering is consistent with hopping of hydrophobes between the nanoscale aggregates as the primary rearrangement mechanism. This rearrangement changes the network conformation that leads to non-affine deformation, where the change in the nanostructure dimension from SAXS is less than 15% of the total macroscopic strain. These nanostructure changes are rate dependent and correlated with the relaxation time of the hydrogel. At low strain rate (0.15% s-1), no significant change of the nanostructure was observed, whereas at higher strain rates (1.5% s-1 and 8.4% s-1) significant nanostructure anisotropy occurred during extension. These differences are attributed to the ability for the network chains to rearrange on the time scale of the deformation; when the characteristic time for extension is longer than the average segmental relaxation time, no significant change in nanostructure occurs on uniaxial extension. These results illustrate the importance of strain rate in the mechanical characterization and consideration of relaxation time in the design of tough hydrogels with reversible crosslinks.


Electronic and optical properties of MAPbX3 perovskites (X = I, Br, Cl): a unified DFT and GW theoretical analysis.
Materials engineering is a key for the enhancement of photovoltaics technology. This is particularly true for the novel class of perovskite solar cells. Accurate theoretical modelling can help establish general trends of behavior when addressing structural changes. Here, we consider the effects due to halide substitution in organohalide CH3NH3PbX3 perovskites exploring the halide series with X = Cl, Br, I. For this task, we use accurate DFT and GW methods including spin-orbit coupling. We find the expected band gap increase when moving from X = I to Cl, in line with the experimental data. Most notably, the calculated absorption coefficients for I, Br and Cl are nicely reproducing the behavior reported experimentally. A common feature of all the simulated band structures is a significant Rashba effect. This is similar for MAPbI3 and MAPbBr3 while MAPbCl3 shows in general a reduced Rashba interaction coefficient. Finally, a monotonic increase of the exciton reduced masses is calculated when moving from I to Br to Cl, in line with the stronger excitonic character of the lighter perovskite halides.


Dopamine receptor antagonists.
Intractable nausea and/or vomiting is a serious and significant clinical dilemma that may greatly detract from quality of life. One of the first classes of antiemetic agents used as well as one of the commonest classes of antiemetic agents used is that of the dopamine receptor antagonists. Dopamine receptor antagonists are useful antiemetic agents, however, unfortunately, clinicians have on occasion resorted to switching from one dopamine receptor antagonist to another dopamine receptor antagonist when the initial dopamine receptor antagonist was ineffective rather than adding on a second antiemetic agent from a totally different class (e.g., 5-HT3 receptor antagonists, NK-1 receptor antagonists).


Modified Granada Agar Medium for the detection of group B Streptococcus carriage in pregnant women.
To improve the detection rate of group B streptococci (GBS) in pregnant women, aiming at the prevention of early-onset septicemia in the newborn. The yield from culturing two sites, vaginal and anorectal, on a Modified Granada Medium (MGM) was compared with our standard approach of culturing a vaginal swab on blood agar (BA). Samples were processed from 430 consecutive pregnant women. GBS was isolated from the vagina in 11.6% with BA, and in 13.7% with MGM. In 17.0% of anorectal samples, GBS was identified with MGM. The combination of both sites and media had a yield of 20.0%. MGM identified all but six (2%) of 310 GBS strains after aerobic incubation, with use of a cover slide, and missed only three strains (1%) after anaerobic incubation. Separate culture of vaginal and anorectal samples using the same MGM agar plate resulted in an increase in detection rate for GBS of 76% as compared to BA alone. The technique is simple and results are available after overnight incubation. MGM was confirmed as a specific medium for the identification of GBS, with a sensitivity of 98-99%.


Complex Interactions between soil-transmitted helminths and malaria in pregnant women on the Thai-Burmese border.
Deworming is recommended by the WHO in girls and pregnant and lactating women to reduce anaemia in areas where hookworm and anaemia are common. There is conflicting evidence on the harm and the benefits of intestinal geohelminth infections on the incidence and severity of malaria, and consequently on the risks and benefits of deworming in malaria affected populations. We examined the association between geohelminths and malaria in pregnancy on the Thai-Burmese border. Routine antenatal care (ANC) included active detection of malaria (weekly blood smear) and anaemia (second weekly haematocrit) and systematic reporting of birth outcomes. In 1996 stool samples were collected in cross sectional surveys from women attending the ANCs. This was repeated in 2007 when malaria incidence had reduced considerably. The relationship between geohelminth infection and the progress and outcome of pregnancy was assessed. Stool sample examination (339 in 1996, 490 in 2007) detected a high prevalence of geohelminths 70% (578/829), including hookworm (42.8% (355)), A. lumbricoides (34.4% (285)) and T.trichuria (31.4% (250)) alone or in combination. A lower proportion of women (829) had mild (21.8% (181)) or severe (0.2% (2)) anaemia, or malaria 22.4% (186) (P.vivax monoinfection 53.3% (101/186)). A. lumbricoides infection was associated with a significantly decreased risk of malaria (any species) (AOR: 0.43, 95% CI: 0.23-0.84) and P.vivax malaria (AOR: 0.29, 95% CI: 0.11-0.79) whereas hookworm infection was associated with an increased risk of malaria (any species) (AOR: 1.66, 95% CI: 1.06-2.60) and anaemia (AOR: 2.41, 95% CI: 1.18-4.93). Hookworm was also associated with low birth weight (AOR: 1.81, 95% CI: 1.02-3.23). A. lumbricoides and hookworm appear to have contrary associations with malaria in pregnancy.


Ca isotopes record rapid crystal growth in volcanic and subvolcanic systems.
Kinetic calcium isotope effects can be used as growth-rate proxies for volcanic and subvolcanic minerals. Here, we analyze Ca isotopic compositions in experimental and natural samples and confirm that large kinetic effects (>2‰) can occur during magmatic plagioclase crystallization. Experiments confirm theoretical predictions that disequilibrium isotope effects depend mainly on the rates for crystal growth relative to liquid phase Ca diffusivity (R/D). Plagioclase phenocrysts from the 1915 Mount Lassen rhyodacite eruption, the ∼650-y-old Deadman Creek Dome eruption, and several mafic subvolcanic orbicules and plagioclase comb layers from Northern California have disequilibrium Ca isotopic compositions that suggest rapid crystal growth rates (>1 cm/y to 15 cm/y). The Ca isotope results, combined with complementary crystal-size distribution analyses, suggest that magmatic rejuvenation (and eruption) events, as reflected in crystal growth times, can be as short as ∼10-3 y. Although mafic systems are predicted to have shorter magmatic rejuvenation periods, we find similarly short timescales in both mafic and silicic systems. These results are consistent with a growing body of evidence suggesting that dominantly crystalline volcanic magma reservoirs can be rapidly reactivated by the injection of fresh magma prior to eruption. By focusing on a common mineral such as plagioclase, this approach can be applied across all major magmatic compositions, suggesting that Ca isotopes can be used as a tool for investigating the dynamics and timing of volcanic eruptions.


Associations of height, leg length, and lung function with cardiovascular risk factors in the Midspan Family Study.
Taller people and those with better lung function are at reduced risk of coronary heart disease (CHD). Biological mechanisms for these associations are not well understood, but both measures may be markers for early life exposures. Some studies have shown that leg length, an indicator of pre-pubertal nutritional status, is the component of height most strongly associated with CHD risk. Other studies show that height-CHD associations are greatly attenuated when lung function is controlled for. This study examines (1) the association of height and the components of height (leg length and trunk length) with CHD risk factors and (2) the relative strength of the association of height and forced expiratory volume in one second (FEV(1)) with risk factors for CHD. Cross sectional analysis of data collected at detailed cardiovascular screening examinations of 1040 men and 1298 women aged 30-59 whose parents were screened in 1972-76. Subjects come from 1477 families and are members of the Midspan Family Study. The towns of Renfrew and Paisley in the West of Scotland. Taller subjects and those with better lung function had more favourable cardiovascular risk factor profiles, associations were strongest in relation to FEV(1). Higher FEV(1) was associated with lower blood pressure, cholesterol, glucose, fibrinogen, white blood cell count, and body mass index. Similar, but generally weaker, associations were seen with height. These associations were not attenuated in models controlling for parental height. Longer leg length, but not trunk length, was associated with lower systolic and diastolic blood pressure. Longer leg length was also associated with more favourable levels of cholesterol and body mass index than trunk length. These findings provide indirect evidence that measures of lung development and pre-pubertal growth act as biomarkers for childhood exposures that may modify an individual's risk of developing CHD. Genetic influences do not seem to underlie height-CHD associations.