The relative importance of different measures of peer smoking on adolescent smoking behavior: cross-sectional and longitudinal analyses of a large British cohort.
To examine the relative importance of smoking behavior of best friends, boyfriends/girlfriends, the wider friendship group, and school year group smoking prevalence as correlates and predictors of smoking behavior (peer influence). The article also aims to assess the relative extent to which smoking behavior is associated with changes in smoking among peers who are selected to be friends (selective association). Using two waves of data collected from 4,145 year 8 (12-13 years) and year 9 (13-14 years) students in 29 schools, logistic regression models estimated the cross-sectional association between four year 8 peer influence variables and weekly and occasional smoking, and the extent to which these peer influence variables and three selective association variables were predictors of weekly smoking in year 9. The smoking behavior of best friend, boyfriend/girlfriend, the wider friendship group, and school year group prevalence were cross-sectionally associated with higher odds of weekly and occasional smoking. In longitudinal multivariate influence models, only the smoking behavior of boyfriend/girlfriend and the wider friendship group were associated with weekly smoking. Weekly smoking was associated with maintaining or changing to having smokers among best friends, boyfriends/girlfriends, and the wider friendship group. In models including all variables, only selective association effects were observed. Although univariate analyses indicate an association of friends', peer group, and year group smoking with current and subsequent smoking behavior, multivariate longitudinal analyses indicate that simple peer influence models do not completely explain adolescent smoking and that a more complex interrelationship exists between smoking, peer's smoking and peer socialization.


Ethanol can contribute to energy and environmental goals.
To study the potential effects of increased biofuel use, we evaluated six representative analyses of fuel ethanol. Studies that reported negative net energy incorrectly ignored coproducts and used some obsolete data. All studies indicated that current corn ethanol technologies are much less petroleum-intensive than gasoline but have greenhouse gas emissions similar to those of gasoline. However, many important environmental effects of biofuel production are poorly understood. New metrics that measure specific resource inputs are developed, but further research into environmental metrics is needed. Nonetheless, it is already clear that large-scale use of ethanol for fuel will almost certainly require cellulosic technology.


Mutability dynamics of an emergent single stranded DNA virus in a naïve host.
Quasispecies variants and recombination were studied longitudinally in an emergent outbreak of beak and feather disease virus (BFDV) infection in the orange-bellied parrot (Neophema chrysogaster). Detailed health monitoring and the small population size (<300 individuals) of this critically endangered bird provided an opportunity to longitudinally track viral replication and mutation events occurring in a circular, single-stranded DNA virus over a period of four years within a novel bottleneck population. Optimized PCR was used with different combinations of primers, primer walking, direct amplicon sequencing and sequencing of cloned amplicons to analyze BFDV genome variants. Analysis of complete viral genomes (n = 16) and Rep gene sequences (n = 35) revealed that the outbreak was associated with mutations in functionally important regions of the normally conserved Rep gene and immunogenic capsid (Cap) gene with a high evolutionary rate (3.41×10(-3) subs/site/year) approaching that for RNA viruses; simultaneously we observed significant evidence of recombination hotspots between two distinct progenitor genotypes within orange-bellied parrots indicating early cross-transmission of BFDV in the population. Multiple quasispecies variants were also demonstrated with at least 13 genotypic variants identified in four different individual birds, with one containing up to seven genetic variants. Preferential PCR amplification of variants was also detected. Our findings suggest that the high degree of genetic variation within the BFDV species as a whole is reflected in evolutionary dynamics within individually infected birds as quasispecies variation, particularly when BFDV jumps from one host species to another.


Gene heterogeneity for tetracycline resistance in Staphylococcus spp.
Nucleotide sequences related to four tet genes were studied by hybridization in 183 clinical Staphylococcus isolates. tet(K) predominated in strains resistant only to tetracycline, while tet(M) was responsible for combined tetracycline and minocycline resistance. In strains harboring both genes, they contributed additively. tet(L) was detected in only five strains, and no hybridization was observed with tet(O).


Patient-specific biomechanical model as whole-body CT image registration tool.
Whole-body computed tomography (CT) image registration is important for cancer diagnosis, therapy planning and treatment. Such registration requires accounting for large differences between source and target images caused by deformations of soft organs/tissues and articulated motion of skeletal structures. The registration algorithms relying solely on image processing methods exhibit deficiencies in accounting for such deformations and motion. We propose to predict the deformations and movements of body organs/tissues and skeletal structures for whole-body CT image registration using patient-specific non-linear biomechanical modelling. Unlike the conventional biomechanical modelling, our approach for building the biomechanical models does not require time-consuming segmentation of CT scans to divide the whole body into non-overlapping constituents with different material properties. Instead, a Fuzzy C-Means (FCM) algorithm is used for tissue classification to assign the constitutive properties automatically at integration points of the computation grid. We use only very simple segmentation of the spine when determining vertebrae displacements to define loading for biomechanical models. We demonstrate the feasibility and accuracy of our approach on CT images of seven patients suffering from cancer and aortic disease. The results confirm that accurate whole-body CT image registration can be achieved using a patient-specific non-linear biomechanical model constructed without time-consuming segmentation of the whole-body images.


Aggregation of topological motifs in the Escherichia coli transcriptional regulatory network.
Transcriptional regulation of cellular functions is carried out through a complex network of interactions among transcription factors and the promoter regions of genes and operons regulated by them. To better understand the system-level function of such networks simplification of their architecture was previously achieved by identifying the motifs present in the network, which are small, overrepresented, topologically distinct regulatory interaction patterns (subgraphs). However, the interaction of such motifs with each other, and their form of integration into the full network has not been previously examined. By studying the transcriptional regulatory network of the bacterium, Escherichia coli, we demonstrate that the two previously identified motif types in the network (i.e., feed-forward loops and bi-fan motifs) do not exist in isolation, but rather aggregate into homologous motif clusters that largely overlap with known biological functions. Moreover, these clusters further coalesce into a supercluster, thus establishing distinct topological hierarchies that show global statistical properties similar to the whole network. Targeted removal of motif links disintegrates the network into small, isolated clusters, while random disruptions of equal number of links do not cause such an effect. Individual motifs aggregate into homologous motif clusters and a supercluster forming the backbone of the E. coli transcriptional regulatory network and play a central role in defining its global topological organization.


Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter.
Molecular dynamics simulations have been used to study the alternate access mechanism of the melibiose transporter from Escherichia coli. Starting from the outward-facing partially occluded form, 2 out of 12 simulations produced an outward full open form and one partially open, whereas the rest yielded fully or partially occluded forms. The shape of the outward-open form resembles other outward-open conformations of secondary transporters. During the transporter opening, conformational changes in some loops are followed by changes in the periplasm region of transmembrane helix 7. Helical curvature relaxation and unlocking of hydrophobic and ionic locks promote the outward opening of the transporter making accessible the substrate binding site. In particular, FRET studies on mutants of conserved aromatic residues of extracellular loop 4 showed lack of substrate binding, emphasizing the importance of this loop for making crucial interactions that control the opening of the periplasmic side. This study indicates that the alternate access mechanism for the melibiose transporter fits better into a flexible gating mechanism rather than the archetypical helical rigid-body rocker-switch mechanism.


Real-world data confirm clinical trial outcomes for rivaroxaban in orthopaedic patients.
Venous thromboembolism (VTE) is a potential cause of morbidity and mortality in patients after major orthopaedic surgery. Based on the results of the international phase III RECORD (Regulation of Coagulation in Orthopaedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) program, the oral, direct Factor Xa inhibitor rivaroxaban has been approved in many countries for the prevention of VTE after elective hip arthroplasty or knee arthroplasty. However, study results of randomized controlled trials may have limited generalizability to routine clinical practice in unselected patients. The phase IV XAMOS (Xarelto® in the Prophylaxis of Postsurgical Venous Throboembolism after Elective Major Orthopaedic Surgery of the Hip or Knee) study and the ORTHO-TEP (large single-center registry) collected real-world data to assess the effectiveness and safety of rivaroxaban compared with standard of care in large cohorts of patients undergoing major orthopaedic surgery. This review evaluates real-world data from XAMOS and ORTHO-TEP, confirming the favorable benefit-risk profile of rivaroxaban for the prevention of VTE in patients after major orthopaedic surgery that was demonstrated by the phase III RECORD studies in patients after elective hip or knee arthroplasty.


Copy number variation analysis in bicuspid aortic valve-related aortopathy identifies TBX20 as a contributing gene.
Bicuspid aortic valve (BAV) is the most common congenital heart defect (CHD), affecting 1-2% of the population. BAV is associated with thoracic aortic aneurysms (TAAs). Deleterious copy number variations (CNVs) were found previously in up to 10% of CHD cases. This study aimed at unravelling the contribution of deleterious deletions or duplications in 95 unrelated BAV/TAA patients. Seven unique or rare CNVs were validated, harbouring protein-coding genes with a role in the cardiovascular system. Based on the presence of overlapping CNVs in patients with cardiovascular phenotypes in the DECIPHER database, the identification of similar CNVs in whole-exome sequencing data of 67 BAV/TAA patients and suggested topological domain involvement from Hi-C data, supportive evidence was obtained for two genes (DGCR6 and TBX20) of the seven initially validated CNVs. A rare variant burden analysis using next-generation sequencing data from 637 BAV/TAA patients was performed for these two candidate genes. This revealed a suggestive genetic role for TBX20 in BAV/TAA aetiology, further reinforced by segregation of a rare TBX20 variant with the phenotype within a BAV/TAA family. To conclude, our results do not confirm a significant contribution for deleterious CNVs in BAV/TAA as only one potentially pathogenic CNV (1.05%) was identified. We cannot exclude the possibility that BAV/TAA is occasionally attributed to causal CNVs though, or that certain CNVs act as genetic risk factors by creating a sensitised background for BAV/TAA. Finally, accumulative evidence for TBX20 involvement in BAV/TAA aetiology underlines the importance of this transcription factor in cardiovascular disease.


[Efficacy of repeated hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma with portal vein tumor thrombosis].
The aim of this study is to elucidate the efficacy of repeated hepatic arterial infusion chemotherapy (HAIC) and different chemotherapeutic regimens for treating patients having advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). From Jan. 1999 and Dec. 2003, a total of 103 patients diagnosed as having HCC with PVTT, but without extrahepatic spreading, were enrolled in this study. They were stratified into two groups. Group I (67 patients) received intraarterial cisplatin (CDDP, 80 mg/m2 for 2 hours on Day 1), Group II (36 patients) received intraarterial CDDP (60 mg/m2 for 2 hours on Day 2) and 5-fluorouracil (5-FU, 500 mg/m2 for 5 hours on Day 1-3). They were scheduled to receive at least three consecutive courses of the HAIC at 1 month intervals. Among the 66 patients who completed the protocol, one (2.5%) and seven (17.5%) patients of group I, and one (3.8%) and four (15.4%) of group II, exhibited complete and partial responses, respectively. The median survival period of all the patients was 6 months. Group II showed a tendency to improve the median survival compared to group I (8.5 vs 5.0 months, respectively, P=0.45). The most common adverse reaction was nausea (58.2%). However, an elevation of the total bilirubin level was more frequent in Group I than in Group II (61.3% vs 20.7%, respectively, P<0.05). Repeated HAIC using CDDP achieved favorable results in a few patients with HCC with PVTT, and additional 5-FU may be useful.


DNA mismatch-specific targeting and hypersensitivity of mismatch-repair-deficient cells to bulky rhodium(III) intercalators.
Mismatch repair (MMR) is critical to maintaining the integrity of the genome, and deficiencies in MMR are correlated with cancerous transformations. Bulky rhodium intercalators target DNA base mismatches with high specificity. Here we describe the application of bulky rhodium intercalators to inhibit cellular proliferation differentially in MMR-deficient cells compared with cells that are MMR-proficient. Preferential inhibition by the rhodium complexes associated with MMR deficiency is seen both in a human colon cancer cell line and in normal mouse fibroblast cells; the inhibition of cellular proliferation depends strictly on the MMR deficiency of the cell. Furthermore, our assay of cellular proliferation is found to correlate with DNA mismatch targeting by the bulky metallointercalators. It is the Delta-isomer that is active both in targeting base mismatches and in inhibiting DNA synthesis. Additionally, the rhodium intercalators promote strand cleavage at the mismatch site with photoactivation, and we observe that the cellular response is enhanced with photoactivation. Targeting DNA mismatches may therefore provide a cell-selective strategy for chemotherapeutic design.


Contribution of impaired myocardial insulin signaling to mitochondrial dysfunction and oxidative stress in the heart.
Diabetes-associated cardiac dysfunction is associated with mitochondrial dysfunction and oxidative stress, which may contribute to left ventricular dysfunction. The contribution of altered myocardial insulin action, independent of associated changes in systemic metabolism, is incompletely understood. The present study tested the hypothesis that perinatal loss of insulin signaling in the heart impairs mitochondrial function. In 8-week-old mice with cardiomyocyte deletion of insulin receptors (CIRKO), inotropic reserves were reduced, and mitochondria manifested respiratory defects for pyruvate that was associated with proportionate reductions in catalytic subunits of pyruvate dehydrogenase. Progressive age-dependent defects in oxygen consumption and ATP synthesis with the substrate glutamate and the fatty acid derivative palmitoyl-carnitine were observed. Mitochondria also were uncoupled when exposed to palmitoyl-carnitine, in part as a result of increased reactive oxygen species production and oxidative stress. Although proteomic and genomic approaches revealed a reduction in subsets of genes and proteins related to oxidative phosphorylation, no reductions in maximal activities of mitochondrial electron transport chain complexes were found. However, a disproportionate reduction in tricarboxylic acid cycle and fatty acid oxidation proteins in mitochondria suggests that defects in fatty acid and pyruvate metabolism and tricarboxylic acid flux may explain the mitochondrial dysfunction observed. Impaired myocardial insulin signaling promotes oxidative stress and mitochondrial uncoupling, which, together with reduced tricarboxylic acid and fatty acid oxidative capacity, impairs mitochondrial energetics. This study identifies specific contributions of impaired insulin action to mitochondrial dysfunction in the heart.


Establishing Myelinating Cocultures Using Human iPSC-Derived Sensory Neurons to Investigate Axonal Degeneration and Demyelination.
Complex signaling between Schwann cells and axons are vital for peripheral neuron development, myelination, and repair. The interaction between these two cell types can be modeled in vitro by coculturing rodent Schwann cells and neurons together. These have in the past been used with great success to help unravel the bidirectional signaling mechanisms that lead to Schwann cell proliferation and myelination. To provide more translatable potential, we have developed myelinating cocultures using human, induced pluripotent stem cell (iPSC)-derived neurons. Under the right conditions, the human neurons are efficiently myelinated by rat Schwann cells, demonstrating successful cross-species signaling. This chapter describes all the necessary steps to generate these myelinating cocultures and methods to investigate and quantify various aspects of myelination. The myelinating cocultures can be maintained in excellent health for over 1 year, facilitating their use to study developmental or chronic disease processes. With this in mind, we have used the cocultures to model a sensory neuropathy which displays clinically with both axonal and demyelinating features. In the cocultures, we found evidence of extensive axonal degeneration and demyelination demonstrated by axonal swelling and fragmentation, and myelin disintegration. The myelinating cocultures can therefore be used to study complex, human disease processes that result in both axonal and myelin-associated degenerative processes.


The fecal presence of enterotoxin and F4 genes as an indicator of efficacy of treatment with colistin sulfate in pigs.
Enterotoxigenic Escherichia coli (ETEC) strains producing multiple enterotoxins are important causes of post-weaning diarrhea (PWD) in pigs. The aim of the present study was to investigate the fecal presence of ETEC enterotoxin as well as F4 and F18 genes as an indicator of colistin sulfate (CS) efficacy for treatment of PWD in pigs. Forty-eight piglets were weaned at the age of 21 days, and were divided into four groups: challenged treated, challenged untreated, unchallenged treated, and unchallenged untreated. Challenge was performed using 109 CFU of an ETEC: F4 strain, and treatment was conducted using oral CS at the dose of 50,000 IU/kg. The fecal presence of genes encoding for STa, STb, LT, F4 and F18 was detected using PCR. The PCR amplification of ETEC virulence genes showed that nearly 100% of pigs excreted genes encoding for STa and STb toxins in the feces before the challenge. These genes, in the absence of the gene encoding F4, were considered as a marker for F4-negative ETEC. One day after ETEC: F4 oral challenge pigs in the two challenged groups excreted the genes encoding LT and F4 in the feces. These genes were considered as a marker for F4-positive ETEC. However, the gene encoding F18 was not detected in any fecal samples of the 4 groups throughout the experiment. After only 3 days of successive oral treatment with CS, a significant reduction in both the F4-positive and negative ETEC populations was observed in the challenged treated group compared to the challenged untreated group (p < 0.0001). Our study is among the first to report that under controlled farming conditions, oral CS treatment had a significant effect on both fecal F4-positive and F4-negative ETEC in pigs. However, CS clinical efficiency was correlated with non-detection of F4-positive ETEC in the feces. Furthermore the fecal presence of F4-negative ETEC was not associated with clinical symptoms of post-weaning diarrhea in pigs.


Fibromyalgia pain and its modulation by hypnotic and non-hypnotic suggestion: an fMRI analysis.
The neuropsychological status of pain conditions such as fibromyalgia, commonly categorized as 'psychosomatic' or 'functional' disorders, remains controversial. Activation of brain structures dependent upon subjective alterations of fibromyalgia pain experience could provide an insight into the underlying neuropsychological processes. Suggestion following a hypnotic induction can readily modulate the subjective experience of pain. It is unclear whether suggestion without hypnosis is equally effective. To explore these and related questions, suggestions following a hypnotic induction and the same suggestions without a hypnotic induction were used during functional magnetic resonance imaging to increase and decrease the subjective experience of fibromyalgia pain. Suggestion in both conditions resulted in significant changes in reported pain experience, although patients claimed significantly more control over their pain and reported greater pain reduction when hypnotised. Activation of the midbrain, cerebellum, thalamus, and midcingulate, primary and secondary sensory, inferior parietal, insula and prefrontal cortices correlated with reported changes in pain with hypnotic and non-hypnotic suggestion. These activations were of greater magnitude, however, when suggestions followed a hypnotic induction in the cerebellum, anterior midcingulate cortex, anterior and posterior insula and the inferior parietal cortex. Our results thus provide evidence for the greater efficacy of suggestion following a hypnotic induction. They also indicate direct involvement of a network of areas widely associated with the pain 'neuromatrix' in fibromyalgia pain experience. These findings extend beyond the general proposal of a neural network for pain by providing direct evidence that regions involved in pain experience are actively involved in the generation of fibromyalgia pain.


Effect of streptozotocin-diabetes on the local and general responses to injury in the rat.
1. The effects of streptozotocin-diabetes on the local and general responses to a 4 h period of bilateral hind-limb ischaemia in the rat have been investigated. The rats were injured 48 h after the intravenous injection of the streptozotocin. 2. Less fluid was lost from the circulation into the injured limbs after injury in the diabetic rats and this was directly related to the severity of the diabetes, but could not be explained by dehydration. However, when the diabetic and nondiabetic injured rats were considered together there was significant negative correlation between either plasma osmolality or plasma glucose concentration and water content in the injured hind limb. 3. The relationship between plasma glucose concentration and plasma osmolality was changed by injury such that, particularly in the injured diabetic rats, plasma osmolality at a given glucose concentration was higher than that predicted from the relationship betweeen these variables in the uninjured rat.


Responsiveness and minimal detectable change of the dynamic gait index and functional gait index in persons with balance and vestibular disorders.
We performed a retrospective chart review to determine the responsiveness and minimal detectable change (MDC95) in persons with balance and vestibular disorders with the dynamic gait index (DGI) and the functional gait assessment (FGA). The study cohort consisted of 326 patients with a mean age of 60 ± 18.3 years (range, 18-95 years; 69% female). The DGI, FGA, Activities-Specific Balance Confidence (ABC) scale, and the dizziness handicap inventory (DHI) were collected at intake and discharge. The standardized response mean as an index of responsiveness was greater for the FGA (1.25) than for the DGI (0.72). Both measures demonstrated good internal consistency with baseline measures. The amount of pre- to posttreatment change that exceeds chance variation was estimated at 4 points for the DGI and 6 points for the FGA. In both the DGI and the FGA, a magnitude of change equivalent to the respective MDC95 was significantly associated with improvements in self-reported disability as measured by the ABC and DHI. The DGI and the FGA are responsive to change over time in persons with balance and vestibular disorders. More complex gait measures need to be developed, as close to 50% of the subjects received optimal scores at discharge from a physical therapy exercise program, indicating that these measures have a ceiling effect.


Contributions of After School Programs to the Development of Fundamental Movement Skills in Children.
Fundamental movement skill (FMS) proficiency or the ability to perform basic skills (e.g., throwing, catching and jumping) has been linked to participation in lifelong physical activity. FMS proficiency amongst children has declined in the previous 15 years, with more children performing FMS at a low-mastery level. These declines may help explain the insufficient levels of participation in health promoting physical activity seen in today's youth. The after school time period (e.g., 3 to 6 p.m.), is increasingly considered an opportune time for physical activity interventions. To date, little research has examined the potential for after school programming to improve FMS proficiency. Participants (n=40, 6-10 years) of two existent physical activity based after school programs, a low-organized games and a sports-based program, were pre- and post-tested for FMS proficiency using the Test of Gross Motor Development-2 (TGMD-2) over an 11-week period. The sports-based program participants showed no improvement in FMS over the 11-week study (p=0.91, eta2=0.00) and the games-based program participants significantly improved their proficiency (p=0.00, eta2=0.30). No significant (p=0.13, eta2 = 0.06), differences were found in change in FMS scores between the low-organized games program participants and the sport-based program participants. These results suggest that after school programs with a low-organized games-based focus may support a moderate improvement in FMS proficiency in young children. Better training of after school program leaders on how to teach FMS may be necessary to assist children in acquiring sufficient proficiency in FMS.


Predicting a nation's olympic-qualifying swimmers.
Talent identification and development typically involve allocation of resources toward athletes selected on the basis of early-career performance. To compare 4 methods for early-career selection of Australia's 2012 Olympic-qualifying swimmers. Performance times from 5738 Australian swimmers in individual Olympic events at 101 competitions from 2000 to 2012 were analyzed as percentages of world-record times using 4 methods that retrospectively simulated early selection of swimmers into a talent-development squad. For all methods, squad-selection thresholds were set to include 90% of Olympic qualifiers. One method used each swimmer's given-year performance for selection, while the others predicted each swimmer's 2012 performance. The predictive methods were regression and neural-network modeling using given-year performance and age and quadratic trajectories derived using mixed modeling of each swimmer's annual best career performances up to the given year. All methods were applied to swimmers in 2007 and repeated for each subsequent year through 2011. The regression model produced squad sizes of 562, 552, 188, 140, and 93 for the years 2007 through 2011. Corresponding proportions of the squads consisting of Olympic qualifiers were 11%, 11%, 32%, 43%, and 66%. Neural-network modeling produced similar outcomes, but the other methods were less effective. Swimming Australia's actual squads ranged from 91 to 67 swimmers but included only 50-74% of Olympic qualifiers. Large talent-development squads are required to include most eventual Olympic qualifiers. Criteria additional to age and performance are needed to improve early selection of swimmers to talent-development squads.


Single-transmembrane domain IGF-II/M6P receptor: potential interaction with G protein and its association with cholesterol-rich membrane domains.
The IGF-II/mannose 6-phosphate (M6P) receptor is a single-transmembrane domain glycoprotein that plays an important role in the intracellular trafficking of lysosomal enzymes and endocytosis-mediated degradation of IGF-II. The receptor may also mediate certain biological effects in response to IGF-II binding by interacting with G proteins. However, the nature of the IGF-II/M6P receptor's interaction with the G protein or with G protein-coupled receptor (GPCR) interacting proteins such as β-arrestin remains unclear. Here we report that [(125)I]IGF-II receptor binding in the rat hippocampal formation is sensitive to guanosine-5'-[γ-thio]triphosphate, mastoparan, and Mas-7, which are known to interfere with the coupling of the classical GPCR with G protein. Monovalent and divalent cations also influenced [(125)I]IGF-II receptor binding. The IGF-II/M6P receptor, as observed for several GPCRs, was found to be associated with β-arrestin 2, which exhibits sustained ubiquitination after stimulation with Leu(27)IGF-II, an IGF-II analog that binds rather selectively to the IGF-II/M6P receptor. Activation of the receptor by Leu(27)IGF-II induced stimulation of extracellular signal-related kinase 1/2 via a pertussis toxin-dependent pathway. Additionally, we have shown that IGF-II/M6P receptors under normal conditions are associated mostly with detergent-resistant membrane domains, but after stimulation with Leu(27)IGF-II, are translocated to the detergent-soluble fraction along with a portion of β-arrestin 2. Collectively these results suggest that the IGF-II/M6P receptor may interact either directly or indirectly with G protein as well as β-arrestin 2, and activation of the receptor by an agonist can lead to alteration in its subcellular distribution along with stimulation of an intracellular signaling cascade.


Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002).
The British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) commissioned this update of the 2002 guidance. The aim, as before, is to provide guidance on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer. This guidance provides some new recommendations for those with inflammatory bowel disease and for those at moderate risk resulting from a family history of colorectal cancer. In other areas guidance is relatively unchanged, but the recent literature was reviewed and is included where appropriate.


Synergistic effect of high charge and energy particle radiation and chronological age on biomarkers of oxidative stress and tissue degeneration: a ground-based study using the vertebrate laboratory model organism Oryzias latipes.
High charge and energy (HZE) particles are a main hazard of the space radiation environment. Uncertainty regarding their health effects is a limiting factor in the design of human exploration-class space missions, that is, missions beyond low earth orbit. Previous work has shown that HZE exposure increases cancer risk and elicits other aging-like phenomena in animal models. Here, we investigate how a single exposure to HZE particle radiation, early in life, influences the subsequent age-dependent evolution of oxidative stress and appearance of degenerative tissue changes. Embryos of the laboratory model organism, Oryzias latipes (Japanese medaka fish), were exposed to HZE particle radiation at doses overlapping the range of anticipated human exposure. A separate cohort was exposed to reference γ-radiation. Survival was monitored for 750 days, well beyond the median lifespan. The population was also sampled at intervals and liver tissue was subjected to histological and molecular analysis. HZE particle radiation dose and aging contributed synergistically to accumulation of lipid peroxidation products, which are a marker of chronic oxidative stress. This was mirrored by a decline in PPARGC1A mRNA, which encodes a transcriptional co-activator required for expression of oxidative stress defense genes and for mitochondrial maintenance. Consistent with chronic oxidative stress, mitochondria had an elongated and enlarged ultrastructure. Livers also had distinctive, cystic lesions. Depending on the endpoint, effects of γ-rays in the same dose range were either lesser or not detected. Results provide a quantitative and qualitative framework for understanding relative contributions of HZE particle radiation exposure and aging to chronic oxidative stress and tissue degeneration.


Case Reports for Topical Treatment of Corneal Ulcers with a New Matrix Therapy Agent or RGTA® in Dogs.
Superficial corneal ulcers that fail to heal within a normal time period and are refractory to conventional therapy in dogs are common in veterinary practice. Different etiologies can lead to this result, including spontaneous chronic corneal epithelial defects (SCCEDs) and ulcerative keratitis associated with bullous keratopathy. Thus, there is an urgent need to find new therapeutic approaches such as matrix therapy replacement. To determine the efficacy of a new ophthalmic treatment (Clerapliq®) for SCCEDs and ulcerative keratitis associated with bullous keratopathy, a total of 11 dogs referred to the clinic because of nonhealing erosive ulcers after a classic primary treatment were enrolled to get this new treatment. Dogs underwent ophthalmic exams and 7 dogs (10 eyes) were diagnosed with superficial ulceration and 4 dogs (5 eyes) with bullous keratopathy due to endothelial dystrophy/degeneration. They received eye drops of Clerapliq® every 3 days until recovery. The results showed that the corneas with recurrences of the ulcers were resolved predominantly by using Clerapliq® every 3 days in 83.3% of the cases during a period of treatment ranging between 6 to 35 days. Therefore, this new approach using matrix therapy regenerating technology in treating superficial ulcers and bullous keratopathy in dogs can be successfully considered as an adjunctive therapy.


Predicting Internet risks: a longitudinal panel study of gratifications-sought, Internet addiction symptoms, and social media use among children and adolescents.
This study used longitudinal panel survey data collected from 417 adolescents at 2 points in time 1 year apart. It examined relationships between Internet risks changes in Time 2 and social media gratifications-sought, Internet addiction symptoms, and social media use all measured at Time 1. By controlling for age, gender, education, and criterion variable scores in Internet addiction at Time 1, entertainment and instant messaging use at Time 1 significantly predicted increased Internet addiction measured at Time 2. The study also controlled for demographics and scores of criterion variables in Internet risks: targeted for harassment, privacy exposed, and pornographic or violent content consumed in Time 1. Gratifications-sought (including status-gaining, expressing opinions, and identity experimentation), Internet addiction symptoms (including withdrawal and negative life consequences), and social media use (in particular, blogs, and Facebook) significantly predicted Internet risk changes in Time 2. These findings suggest that, with their predictive power, these predictors at Time 1 could be used to identify those adolescents who are likely to develop Internet addiction symptoms and the likelihood of experiencing Internet risks based on their previous gratifications-sought, previous addiction symptoms, and their habits of social media use at Time 1.


Is the early visual system optimised to be energy efficient?
This paper demonstrates that a representation which balances natural image encoding with metabolic energy efficiency shows many similarities to the neural organisation observed in the early visual system. A simple linear model was constructed that learned receptive fields by optimally balancing information coding with metabolic expense for an entire visual field in a 2-stage visual system. The input to the model consists of a space variant retinal array of photoreceptors. Natural images were then encoded through a bottleneck such as the retinal ganglion cells that form the optic nerve. The natural images represented by the activity of retinal ganglion cells were then encoded by many more 'cortical' cells in a divergent representation. Qualitatively, the system learnt by optimising information coding and energy expenditure and matched (1) the centre surround organisation of retinal ganglion cells; (2) the Gabor-like organisation of cortical simple cells; (3) higher densities of receptive fields in the fovea decreasing in the periphery; (4) smaller receptive fields in the fovea increasing in size in the periphery; (5) spacing ratios of retinal cells; and (6) aspect ratios of cortical receptive fields. Quantitatively, however, there are small but significant discrepancies between density slopes which may be accounted for by taking optic blur and fixation induced image statistics into account. In addition, the model cortical receptive fields are more broadly tuned than biological cortical neurons; this may be accounted for by the computational limitation of modelling a relatively low number of neurons. This paper shows that retinal receptive field properties can be understood in terms of balancing coding with synaptic energy expenditure and cortical receptive fields with firing rate energy expenditure, and provides a sound biological explanation of why 'sparse' distributions are beneficial.


A molecular-based approach for examining responses of eukaryotes in microcosms to contaminant-spiked estuarine sediments.
Ecotoxicological information for most contaminants is limited to a small number of taxa, and these are generally restricted to comparatively hardy organisms that are readily extractable from test media and easily identifiable. Advances in DNA sequencing can now provide a comprehensive view of benthic invertebrate diversity. The authors applied 454 pyrosequencing to examine the responses of benthic communities in microcosms exposed to sediments with elevated concentrations of triclosan, the endpoint being eukaryl communities that have successfully vertically migrated through the manipulated sediments. The biological communities associated with the 3 treatments (control triclosan, low triclosan [14 mg/kg], and high triclosan [180 mg/kg]) clustered into 3 groups: control/low (n = 6 controls and 4 low), moderate (n = 2 low), and high (n = 5 high). One sample was discarded as an outlier. The most pronounced change as a response to triclosan was the loss of number of metazoan operational taxonomic units (OTUs), indicative of the control/low and moderate groups, with this being most evident in the range of taxa associated with the classes Chromadorea and Bivalvia and the phylum Kinorhyncha. The authors also describe a range of other taxa that aided discrimination between the groups; compare findings with traditionally obtained meio- and macrofaunal communities obtained from the same experiment; and illustrate some of the advantages and limitations associated with both the molecular and traditional approaches. The described approach illustrates the capacity for amplicon sequencing to provide ecologically relevant information that can be used to strengthen an understanding of how sedimentary communities respond to a range of environmental stressors.


The metabolic enzyme CTP synthase forms cytoskeletal filaments.
Filament-forming cytoskeletal proteins are essential for the structure and organization of all cells. Bacterial homologues of the major eukaryotic cytoskeletal families have now been discovered, but studies suggest that yet more remain to be identified. We demonstrate that the metabolic enzyme CTP synthase (CtpS) forms filaments in Caulobacter crescentus. CtpS is bifunctional, as the filaments it forms regulate the curvature of C. crescentus cells independently of its catalytic function. The morphogenic role of CtpS requires its functional interaction with the intermediate filament, crescentin (CreS). Interestingly, the Escherichia coli CtpS homologue also forms filaments both in vivo and in vitro, suggesting that CtpS polymerization may be widely conserved. E. coli CtpS can replace the enzymatic and morphogenic functions of C. crescentus CtpS, indicating that C. crescentus has adapted a conserved filament-forming protein for a secondary role. These results implicate CtpS as a novel bifunctional member of the bacterial cytoskeleton and suggest that localization and polymerization may be important properties of metabolic enzymes.


Influence of environmental factors on college alcohol drinking patterns.
Alcohol abuse is a major problem, especially among students on and around college campuses. We use the mathematical framework of [16] and study the role of environmental factors on the long term dynamics of an alcohol drinking population. Sensitivity and uncertainty analyses are carried out on the relevant functions (for example, on the drinking reproduction number and the extinction time of moderate and heavy drinking because of interventions) to understand the impact of environmental interventions on the distributions of drinkers. The reproduction number helps determine whether or not the high-risk alcohol drinking behavior will spread and become persistent in the population, whereas extinction time of high-risk drinking measures the effectiveness of control programs. We found that the reproduction number is most sensitive to social interactions, while the time to extinction of high-risk drinkers is significantly sensitive to the intervention programs that reduce initiation, and the college drop-out rate. The results also suggest that in a population, higher rates of intervention programs in low-risk environments (more than intervention rates in high-risk environments) are needed to reduce heavy drinking in the population.


Hexose-6-phosphate dehydrogenase: a new risk gene for multiple sclerosis.
A recent genome-wide association study (GWAS) performed by the The Wellcome Trust Case-Control Consortium based on 12 374 nonsynonymous single-nucleotide polymorphisms (SNPs) provided evidence for several genes involved in multiple sclerosis (MS) susceptibility. In this study, we aimed at verifying the association of 19 SNPs with MS, with P-values < or =0.005, in an independent cohort of 732 patients and 974 controls, all Caucasian from the South of Spain. We observed an association of the rs17368528 polymorphism with MS (P=0.04, odds ratio (OR)=0.801, 95% confidence interval (CI)=0.648-0.990). The association of this polymorphism with MS was further validated in an independent set of 1318 patients from the Canadian Collaborative Project (P=0.04, OR=0.838, 95% CI=0.716-0.964). This marker is located on chromosome 1p36.22, which is 1 Mb away from the MS-associated kinesin motor protein KIF1B, although linkage disequilibrium was not observed between these two markers. The rs17368528 SNP results in an amino-acid substitution (proline to leucine) in the fifth exon of the hexose-6-phosphate dehydrogenase (H6PD) gene, in which some variants have been reported to attenuate or abolish H6PD activity, in individuals with cortisone reductase deficiency. This study corroborates the association of one locus determined by GWAS and points to H6PD as a new candidate gene for MS.


The Interaction Between Gaze and Facial Expression in the Amygdala and Extended Amygdala is Modulated by Anxiety.
Behavioral evidence indicates that angry faces are seen as more threatening, and elicit greater anxiety, when directed at the observer, whereas the influence of gaze on the processing of fearful faces is less consistent. Recent research has also found inconsistent effects of expression and gaze direction on the amygdala response to facial signals of threat. However, such studies have failed to consider the important influence of anxiety on the response to signals of threat; an influence that is well established in behavioral research and recent neuroimaging studies. Here, we investigated the way in which individual differences in anxiety would influence the interactive effect of gaze and expression on the response to angry and fearful faces in the human extended amygdala. Participants viewed images of fearful, angry and neutral faces, either displaying an averted or direct gaze. We found that state anxiety predicted an increased response in the dorsal amygdala/substantia innominata (SI) to angry faces when gazing at, relative to away from the observer. By contrast, high state anxious individuals showed an increased amygdala response to fearful faces that was less dependent on gaze. In addition, the relationship between state anxiety and gaze on emotional intensity ratings mirrored the relationship between anxiety and the amygdala/SI response. These results have implications for understanding the functional role of the amygdala and extended amygdala in processing signals of threat, and are consistent with the proposed role of this region in coding the relevance or significance of a stimulus to the observer.


Disentangling orthorexia nervosa from healthy eating and other eating disorder symptoms: Relationships with clinical impairment, comorbidity, and self-reported food choices.
Orthorexia nervosa (ON) is characterized by obsessions about eating healthily and rigid adherence to a perceived healthy diet. This study uses the Eating Habits Questionnaire to investigate the relationship of ON symptoms with self-reported food intake, eating-related impairment, obsessive compulsive disorder symptoms (OCD), gender, and BMI while controlling for other eating disordered symptoms. The aim of this study is to provide further evidence for the construct of ON as distinct from other forms of disordered eating. The sample consisted of 449 adults recruited on Amazon's Mechanical Turk. Self-reported symptoms of currently recognized eating disorders (anorexia and bulimia nervosa, AN/BN, avoidant/restrictive food intake disorder, ARFID) were statistically controlled in correlational analyses and MANCOVA exploring the relationship of ON domains to comorbidity, eating behavior, gender, and weight. Confirmatory factor analysis supported a three-factor solution for the EHQ, with factors representing normative healthy eating behaviors ("behaviors"), positive feelings associated with healthy eating ("feelings"), and interference/problems from rigid healthy eating ("problems"). Overall ON symptoms were more strongly related to AN/BN than to ARFID. Of the subscales, only Problems was related to other eating disorder symptomatology. Controlling for other eating disorder symptoms, overall ON symptomatology was not related to clinical impairment from eating or OCD, although it was related to higher self-reported intake of fruits/vegetables and lower intake of discretionary foods. When other eating disordered symptoms and ON domains were statistically controlled, Problems was related to clinical eating impairment, OCD symptoms, and higher intake of both fruits/vegetables and discretionary foods. The Problems scale of the EHQ appears to capture disordered eating symptomatology that is distinct from other eating disorders and from normative healthy eating behaviors, consistent with descriptions of ON.


The World Report on Disability and communication disability: some considerations from an Indian context.
The aim of this paper is to reflect and comment on the lead article by Wylie, McAllister, Davidson, and Marshall (2013) with reference to people with communication disability in India and illustrated by the work of one Indian non-governmental organization. Key themes and questions from Wylie et al. are identified and discussed. Suggestions for how the recommendations of the World Report on Disability might be implemented in an Indian context are made, notwithstanding the magnitude and scale of the demand for services in the context of the vast population. Nine recommendations at the meso- and micro-level are included. These emphasize three major themes: methodologies to ensure access for all those who need speech-language pathology services; enhancement of speech-language pathology training capacities to deliver holistic professional services in urban and rural settings; promotion of the involvement of advocacy groups in policy-making and, hence, facilitating people with communication needs to be more assertive about rights and entitlement.


Modification of the Bankart reconstruction using a suture anchor.
A prospective study was done to determine the effectiveness of a suture anchor in doing a Modified Bankart Reconstruction on the traumatic unidirectional Bankart lesion shoulder. From 1989 to 1991, 26 patients encompassing 27 shoulders with recurrent instability had modified Bankart reconstructions. A minimum 18-month follow-up was obtained by examination of 24 patients with telephone interviews done on two patients. The average follow-up was 23.6 months. A 93.1% good-to-excellent result was obtained using the Bankart rating scale. There were no failures or complications. The surgeon involved in the study thought the suture anchor facilitated the attachment of the avulsed capsulolabral complex in doing the Bankart procedure.


Ultrasound-guided hip injections: a comparative study with fluoroscopy-guided injections.
The purpose was to assess ultrasound-guided injections through patient satisfaction in a comparative internally controlled study of fluoroscopic versus ultrasound technique and to quantitate the reliability of the ultrasound method. In addition, the reliability of the ultrasound method was quantitated. This study consisted of the first 50 consecutive patients to undergo ultrasound-guided intra-articular injection of the hip (by a nurse practitioner) and who had previously undergone fluoroscopy-guided intra-articular injections by our center's fellowship-trained musculoskeletal radiologists. The patients rated the ultrasound and fluoroscopic experiences on a scale from 1 to 10 for convenience and pain; in addition, they indicated their preference between the 2 techniques. Success of the injection was documented among a total of 206 consecutive patients who underwent ultrasound-guided injections during the period of the controlled study. For convenience, ultrasound injection had a mean rating of 9.8 whereas fluoroscopic injection had a mean rating of 3.1. For pain, ultrasound had a mean rating of 3 and fluoroscopy had a mean rating of 5.6. These differences were statistically significant (P < .01) in favor of ultrasound. For preference, 49 of 50 patients in the control study (98%) stated that they would prefer the ultrasound injection, whereas 1 was uncertain. The injection was successful in 202 of the first 206 patients (98%) to undergo ultrasound injection, whereas 4 patients required a second pass for successful injection. In this study in-office ultrasound-guided injections of the hip were more convenient and less painful than fluoroscopy-guided hospital-based injections and were preferred by patients who have undergone both. Furthermore, the ultrasound-guided injections were performed by a recently trained physician extender in contrast to the fluoroscopic method, which was performed by experienced fellowship-trained musculoskeletal radiologists. The procedure is highly successful in the hands of a properly trained clinician. Level II, prospective comparative study.


Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis.
Gastric cancer is strongly associated with Helicobacter pylori (H. pylori). We conducted a previous systematic review and meta-analysis that suggested eradication therapy reduced future incidence of gastric cancer, but effect size was uncertain, and there was no reduction in gastric cancer-related mortality. We updated this meta-analysis, as more data has accumulated. We also evaluated impact of eradication therapy on future risk of gastric cancer in patients having endoscopic mucosal resection for gastric neoplasia. We searched the medical literature through February 2020 to identify randomised controlled trials (RCTs) examining effect of eradication therapy on subsequent occurrence of gastric cancer in healthy H. pylori-positive adults, and in H. pylori-positive patients with gastric neoplasia undergoing endoscopic mucosal resection. The control arm received placebo or no treatment. Follow-up was for ≥2 years. We estimated the relative risk (RR) number needed to treat (NNT), and evaluated the disability-adjusted life-years (DALYs) gained from screening from the meta-analysis. We identified 10 RCTs, seven recruited 8323 healthy individuals, and three randomised 1841 patients with gastric neoplasia. In healthy individuals, eradication therapy reduced incidence of gastric cancer (RR=0.54; 95% CI 0.40 to 0.72, NNT=72), and reduced mortality from gastric cancer (RR=0.61; 95% CI 0.40 to 0.92, NNT=135), but did not affect all-cause mortality. These data suggest that 8 743 815 DALYs (95% CI 5 646 173 to 11 847 456) would be gained if population screening and treatment was implemented globally. In patients with gastric neoplasia, eradication therapy also reduced incidence of future gastric cancer (RR=0.49; 95% CI 0.34 to 0.70, NNT=21). Adverse events were incompletely reported. There is moderate evidence to suggest that H. pylori eradication therapy reduces the incidence of gastric cancer in healthy individuals and patients with gastric neoplasia in East Asian countries. There also appears to be a reduction in gastric cancer-related mortality.


Interplay between surface chemistry and performance of rutile-type catalysts for halogen production.
Catalytic HBr oxidation is an integral step in the bromine-mediated functionalisation of alkanes to valuable chemicals. This study establishes the relationships between the mechanism of HBr oxidation over rutile-type oxides (RuO2, IrO2, TiO2) and their apparent catalytic performance. Comparison with the well-studied HCl oxidation revealed distinct differences in surface chemistry between HBr and HCl oxidation that impact the stability and activity of the catalysts. The kinetic fingerprints of both oxidation reactions over the three rutile-type oxides investigated are compared using temporal analysis of products, which substantiates the energy profiles derived from density functional theory. The quantitative determination of the halogen uptake under operando conditions using prompt gamma activation analysis demonstrates that RuO2 suffers from extensive subsurface bromination upon contact with hydrogen bromide, particularly at low temperature and low O2 : HBr ratios, which negatively affects the stability of the catalyst. TiO2 exhibits intrinsically low halogen coverage (30-50%) under all the conditions investigated, due to its unique defect-driven mechanism that renders it active and stable for Br2 production. On the contrary, for HCl oxidation TiO2 is inactive, and the chlorination of the highly active RuO2 is limited to the surface. Differences in the extent of surface halogenation of the materials were also confirmed by high-resolution transmission electron microscopy and explained by the DFT calculations. These insights into the molecular-level processes taking place under working conditions pave the way for the design of the next generation catalysts for bromine production.


NetTCR-2.0 enables accurate prediction of TCR-peptide binding by using paired TCRα and β sequence data.
Prediction of T-cell receptor (TCR) interactions with MHC-peptide complexes remains highly challenging. This challenge is primarily due to three dominant factors: data accuracy, data scarceness, and problem complexity. Here, we showcase that "shallow" convolutional neural network (CNN) architectures are adequate to deal with the problem complexity imposed by the length variations of TCRs. We demonstrate that current public bulk CDR3β-pMHC binding data overall is of low quality and that the development of accurate prediction models is contingent on paired α/β TCR sequence data corresponding to at least 150 distinct pairs for each investigated pMHC. In comparison, models trained on CDR3α or CDR3β data alone demonstrated a variable and pMHC specific relative performance drop. Together these findings support that T-cell specificity is predictable given the availability of accurate and sufficient paired TCR sequence data. NetTCR-2.0 is publicly available at https://services.healthtech.dtu.dk/service.php?NetTCR-2.0 .


Genome sequencing and analysis of the model grass Brachypodium distachyon.
Three subfamilies of grasses, the Ehrhartoideae, Panicoideae and Pooideae, provide the bulk of human nutrition and are poised to become major sources of renewable energy. Here we describe the genome sequence of the wild grass Brachypodium distachyon (Brachypodium), which is, to our knowledge, the first member of the Pooideae subfamily to be sequenced. Comparison of the Brachypodium, rice and sorghum genomes shows a precise history of genome evolution across a broad diversity of the grasses, and establishes a template for analysis of the large genomes of economically important pooid grasses such as wheat. The high-quality genome sequence, coupled with ease of cultivation and transformation, small size and rapid life cycle, will help Brachypodium reach its potential as an important model system for developing new energy and food crops.


Intermittent androgen suppression for prostate cancer: Canadian Prospective Trial and related observations.
The Canadian Prospective Trial of intermittent androgen suppression was a prototype therapeutic initiative started in 1995 for the management of patients in biochemical relapse after radiation for localized prostate cancer. An interim analysis has yielded several observations on the relations between baseline serum prostate specific antigen (PSA), nadir serum PSA, Gleason score, and time off-treatment. In a typical androgen-dependent tumor, the response of serum PSA to androgen withdrawal is biphasic, but with early tumor progression, plateauing of serum PSA is observed. Ligand-independent activation of the androgen receptor, a mechanism subserving the initiation of androgen independence, can be counteracted experimentally with decoy molecules and clinically with nonsteroidal antiandrogens. In some patients, it is possible to lengthen the off-treatment interval by inhibiting the enzyme 5 alpha-reductase, an effect that can be reinforced by lowering serum testosterone with an antigonadotropin. Serial measurements of serum PSA indicate that intermittent androgen suppression engenders a more diverse range of hormone-related responses than previously appreciated. These include: (1) repeated differentiation of tumor with recovery of apoptotic potential; (2) inhibition of tumor growth by rapid restoration of serum testosterone; and (3) restraint of tumor growth by subnormal levels of serum testosterone. These responses are aspects of regulation that should be taken into account when planning long-term treatment of prostate cancer with intermittent androgen suppression.


Dose-response relationships for the onset of avoidance of sonar by free-ranging killer whales.
Eight experimentally controlled exposures to 1-2 kHz or 6-7 kHz sonar signals were conducted with four killer whale groups. The source level and proximity of the source were increased during each exposure in order to reveal response thresholds. Detailed inspection of movements during each exposure session revealed sustained changes in speed and travel direction judged to be avoidance responses during six of eight sessions. Following methods developed for Phase-I clinical trials in human medicine, response thresholds ranging from 94 to 164 dB re 1 μPa received sound pressure level (SPL) were fitted to Bayesian dose-response functions. Thresholds did not consistently differ by sonar frequency or whether a group had previously been exposed, with a mean SPL response threshold of 142 ± 15 dB (mean ± s.d.). High levels of between- and within-individual variability were identified, indicating that thresholds depended upon other undefined contextual variables. The dose-response functions indicate that some killer whales started to avoid sonar at received SPL below thresholds assumed by the U.S. Navy. The predicted extent of habitat over which avoidance reactions occur depends upon whether whales responded to proximity or received SPL of the sonar or both, but was large enough to raise concerns about biological consequences to the whales.


Combined Drought and Heat Activates Protective Responses in Eucalyptus globulus That Are Not Activated When Subjected to Drought or Heat Stress Alone.
Aiming to mimic a more realistic field condition and to determine convergent and divergent responses of individual stresses in relation to their combination, we explored physiological, biochemical, and metabolomic alterations after drought and heat stress imposition (alone and combined) and recovery, using a drought-tolerant Eucalyptus globulus clone. When plants were exposed to drought alone, the main responses included reduced pre-dawn water potential (Ψpd) and gas exchange. This was accompanied by increases in malondialdehyde (MDA) and total glutathione, indicative of oxidative stress. Abscisic acid (ABA) levels increased while the content of jasmonic acid (JA) fell. Metabolic alterations included reductions in the levels of sugar phosphates accompanied by increases in starch and non-structural carbohydrates. Levels of α-glycerophosphate and shikimate were also reduced while free amino acids increased. On the other hand, heat alone triggered an increase in relative water content (RWC) and Ψpd. Photosynthetic rate and pigments were reduced accompanied by a reduction in water use efficiency. Heat-induced a reduction of salicylic acid (SA) and JA content. Sugar alcohols and several amino acids were enhanced by the heat treatment while starch, fructose-6-phosphate, glucose-6-phosphate, and α-glycerophosphate were reduced. Contrary to what was observed under drought, heat stress activated the shikimic acid pathway. Drought-stressed plants subject to a heat shock exhibited a sharp decrease in gas exchange, Ψpd and JA, no alterations in electrolyte leakage, MDA, starch, and pigments and increased glutathione pool in relation to control. Comparing this with drought stress alone, subjecting drought stressed plants to an additional heat stress alleviated Ψpd and MDA, maintained an increased glutathione pool and reduced starch content and non-structural carbohydrates. A novel response triggered by the combined stress was the accumulation of cinnamate. Regarding recovery, most of the parameters affected by each stress condition reversed after re-establishment of control growing conditions. These results highlight that the combination of drought and heat provides significant protection from more detrimental effects of drought-stressed eucalypts, confirming that combined stress alter plant metabolism in a novel manner that cannot be extrapolated by the sum of the different stresses applied individually.


A randomized trial of intrapartum electronic fetal heart rate monitoring versus intermittent auscultation.
To determine whether continuous intrapartum electronic fetal heart rate monitoring (EFM) is associated with decreased perinatal mortality and morbidity compared with intermittent auscultation. The study was conducted simultaneously at two university hospitals in Athens, Greece (Alexandra and Marika Iliadi Hospitals) from October 1, 1990 to June 30, 1991. All patients with singleton living fetuses and gestational ages of 26 weeks or greater were eligible for inclusion. The participants were assigned to continuous EFM or intermittent auscultation based on the flip of a coin. Both groups were followed during labor according to the most recent ACOG guidelines. However, fetal scalp blood pH and crossover from one group to the other were not used. A total of 1428 patients were included, 746 in the EFM group and 682 in the auscultation group. There were no differences between the groups in terms of maternal age, gravidity, parity, gestational age, and number of antepartum high-risk factors. More patients monitored electronically received oxytocin for either augmentation (52.4 versus 38.1%; P = .0001) or induction (15.6 versus 7%; P = .0001). The length of labor was longer in the EFM group (first stage 6.1 +/- 4.3 versus 5.5 +/- 3.7 hours; P = .006; second stage 29.4 +/- 18.6 versus 26.9 +/- 16.9 minutes; P = .01). There was a higher incidence of nonreassuring fetal heart rate patterns in the EFM group (23.4 versus 10.7%; P = .0001) and a higher rate of surgical intervention (11.2 versus 4.8%; P = .0001). This difference pertained to both vacuum extraction (5.8 versus 2.4%; P = .002) and cesarean delivery for suspected fetal distress (5.3 versus 2.3%; P = .005). There were no differences in 1- and 5-minute Apgar scores, fetal acidosis at birth, need for neonatal resuscitation, neonatal intensive care unit admission, use of assisted ventilation, neonatal hospital stay, or any other neonatal complications. Two neonatal deaths occurred in the EFM group and nine perinatal deaths in the auscultation group (two intrapartum and seven neonatal deaths). The perinatal mortality rates were 2.6 per 1000 and 13 per 1000 total births, respectively (P = .04). The two deaths in the EFM group and three of the neonatal deaths in the auscultation group may not have been prevented by intrapartum monitoring; however, four neonatal deaths from the auscultation group occurred in depressed (5-minute Apgar scores less than 7), acidotic (cord artery pH at or below 7.13) infants. The perinatal death rate related to fetal hypoxia was significantly less in the EFM group (zero of 746 versus six of 682; P = .03). In this controlled trial, intrapartum EFM, as the primary and only method of intrapartum fetal surveillance, was associated with decreased perinatal mortality due to fetal hypoxia but also with higher rates of surgical intervention for suspected fetal distress.


Cell wall oxalate oxidase modifies the ferulate metabolism in cell walls of wheat shoots.
Oxalate oxidase (OXO) utilizes oxalate to generate hydrogen peroxide, and thereby acts as a source of hydrogen peroxide. The present study was carried out to investigate whether apoplastic OXO modifies the metabolism of cell wall-bound ferulates in wheat seedlings. Histochemical staining of OXO showed that cell walls were strongly stained, indicating the presence of OXO activity in shoot walls. When native cell walls prepared from shoots were incubated with oxalate or hydrogen peroxide, the levels of ester-linked diferulic acid (DFA) isomers were significantly increased. On the other hand, the level of ester-linked ferulic acid (FA) was substantially decreased. The decrease in FA level was accounted neither by the increases in DFA levels nor by the release of FA from cell walls during the incubation. After the extraction of ester-linked ferulates, considerable ultraviolet absorption remained in the hemicellulosic and cellulose fractions, which was increased by the treatment with oxalate or hydrogen peroxide. Therefore, a part of FA esters may form tight linkages within cell wall architecture. These results suggest that cell wall OXO is capable of modifying the metabolism of ester-linked ferulates in cell walls of wheat shoots by promoting the peroxidase action via supply of hydrogen peroxide.


Milder forms of atherogenic dyslipidemia in ovulatory versus anovulatory polycystic ovary syndrome phenotype.
Dyslipidemia is common in women with polycystic ovary syndrome (PCOS) but its prevalence in different PCOS phenotypes is still largely unknown. We measured plasma lipids and lipoproteins in 35 anovulatory PCOS (age: 25 +/- 6 years, BMI: 28 +/- 6 kg/m(2)), 15 ovulatory PCOS (age: 30 +/- 6 years, BMI: 25 +/- 3 kg/m(2)) and 27 healthy women (controls) age- and BMI-matched with ovulatory PCOS. PCOS was diagnosed by the presence of clinical or biologic hyperandrogenism associated with chronic anovulation and/or polycystic ovaries at ultrasound. In women with normal menses chronic anovulation was indicated by low serum progesterone levels (<9.54 nmol/l) during midluteal phase (days 21-24) in two consecutive menstrual cycles. Total cholesterol, triglycerides and low-density lipoprotein (LDL)-cholesterol levels increased and high-density lipoprotein (HDL)-cholesterol decreased from controls to ovulatory and then to anovulatory PCOS (all P < 0.05). Levels of lipoprotein(a) (Lp(a)) and small, dense LDL increased (P < 0.0001 for both) and LDL size reduced (P < 0.005) between groups. Insulin resistance (by HOMA) showed a positive correlation with triglycerides and small, dense LDL and an inverse correlation with HDL-cholesterol and LDL size (P < 0.05 for all) in both PCOS phenotypes. No significant correlations were found with testosterone levels. At multivariate analysis, insulin resistance was independently associated with HDL-cholesterol and small, dense LDL in both PCOS phenotypes and with triglyceride concentrations in ovulatory PCOS only. Women with ovulatory PCOS showed milder forms of atherogenic dyslipidemia than anovulatory PCOS and this seemed to be related to the extent of insulin resistance. Future prospective studies are needed to assess the relative contribution of such alterations on cardiovascular risk.


Physiological modules for generating discrete and rhythmic movements: component analysis of EMG signals.
A central question in Neuroscience is that of how the nervous system generates the spatiotemporal commands needed to realize complex gestures, such as handwriting. A key postulate is that the central nervous system (CNS) builds up complex movements from a set of simpler motor primitives or control modules. In this study we examined the control modules underlying the generation of muscle activations when performing different types of movement: discrete, point-to-point movements in eight different directions and continuous figure-eight movements in both the normal, upright orientation and rotated 90°. To test for the effects of biomechanical constraints, movements were performed in the frontal-parallel or sagittal planes, corresponding to two different nominal flexion/abduction postures of the shoulder. In all cases we measured limb kinematics and surface electromyographic activity (EMG) signals for seven different muscles acting around the shoulder. We first performed principal component analysis (PCA) of the EMG signals on a movement-by-movement basis. We found a surprisingly consistent pattern of muscle groupings across movement types and movement planes, although we could detect systematic differences between the PCs derived from movements performed in each shoulder posture and between the principal components associated with the different orientations of the figure. Unexpectedly we found no systematic differences between the figure eights and the point-to-point movements. The first three principal components could be associated with a general co-contraction of all seven muscles plus two patterns of reciprocal activation. From these results, we surmise that both "discrete-rhythmic movements" such as the figure eight, and discrete point-to-point movement may be constructed from three different fundamental modules, one regulating the impedance of the limb over the time span of the movement and two others operating to generate movement, one aligned with the vertical and the other aligned with the horizontal.


Preferences for seeking effort or reward information bias the willingness to work.
Research suggests that the temporal order in which people receive information about costs and benefits whilst making decisions can influence their choices. But, do people have a preference for seeking information about costs or benefits when making effort-based decisions, and does this impact motivation? Here, participants made choices about whether to exert different levels of physical effort to obtain different magnitudes of reward, or rest for low reward. Prior to each effort-based choice, they also had to decide which information they wanted to see first: how much physical effort would be required, or how large the reward would be. We found no overall preference for seeking reward or effort information first, but motivation did change when people saw reward or effort information first. Seeking effort information first, both someone's average tendency to do so and their choice to see effort first on a given trial, was associated with reductions in the willingness to exert higher effort. Moreover, the tendency to prefer effort information first was associated with reduced vigorous exercise and higher levels of fatigue in everyday life. These findings highlight that preferences for seeking effort information may be a bias that reduces people's willingness to exert effort in the lab and in everyday life.


Outcome of childhood brain tumors in Serbia.
To present the results of treatment for childhood brain tumors in Serbia. The medical records of patients with brain tumors diagnosed and operated at the Institute of Neurosurgery, Clinical Center of Serbia and treated with postoperative radiotherapy and chemotherapy at the Institute of Oncology and Radiology of Serbia, Belgrade, between January 1995 and December 2004, were reviewed. Of the 247 patients who were identified, 212 formed the basis of this study. Overall survival (OS) was determined by the Kaplan-Maier method, using log-rank test for comparisons. With a mean follow up of 46.9-33.6 months (range 7-120), the 5-and 8-year OS rates were 70.0% and 61.5%, respectively. At the time of evaluation 119 (60.1%) patients had no evidence of disease. Among 79 patients who failed therapy, most of them (n=61; 77.2%) had local failure only. According to histologic tumor type most of them (n=27; 34.2%) were in the group of malignant medulloblastoma. Girls had better survival than boys, but without statistical significance (p=0.185). Also, no significant difference in survival in relation to age was seen (p=0.291). Patients with supratentorial tumors had significantly better survival than those with infratentorial localizations (p=0.036). Patients with low grade astrocytomas had significantly better survival than malignant gliomas, ependymomas and primitive neuroectodermal tumors (PNETs) (p=0.0001). OS rates were concordant with the results of other modern series. Although the survival rates were encouraging, there is still significant room for improvement in the management of childhood brain tumors.


Evaluation of HIV type 1 strains in men having sex with men and in female sex workers in Mombasa, Kenya.
We compared HIV-1 strains in incident and prevalent infections in a cohort of men having sex with men (MSM) and female sex workers (FSW) near Mombasa, Kenya and conducted a cross-sectional study of viral isolates from a sample of HIV-1-infected MSM and FSW in Kilifi, Coast Province, Kenya. RNA extracted from plasma of 13 MSM, 9 FSW, and one heterosexual male was amplified by nested RT-PCR and the products were directly sequenced. HIV-1 strains from 21 individuals were characterized with one or more complete genome sequences, and two were sequenced in the Nef gene. The envelope quasispecies was also studied in one individual. Among MSM, eight strains were subtype A and five were recombinant. There were two epidemiologically linked pairs of sequences; one pair was subtype A and the other pair was a complex AA2CD recombinant of identical structure. Another MSM was dually infected with DG recombinant strains of related, but nonidentical, structure. MSM also harbored AC and AD recombinant strains. The FSW harbored seven subtype A strains, an AD recombinant, and an AA2D strain related to CRF16_A2D. The one heterosexual male studied had a subtype A infection. This MSM epidemic in Kenya appears to be of local origin, harboring many strains typical of the broader Kenyan epidemic. Characteristics of a close social network were identified, with extended chains of transmission, novel recombinant strains possibly generated within the network, and a relatively high proportion of recombinant and dual infections.


Degree of angle closure and extent of peripheral anterior synechiae: an anterior segment OCT study.
To evaluate the relationship between angle width as determined by anterior segment optical coherence tomography (AS-OCT) and the presence of peripheral anterior synechiae (PAS). This was a prospective observational case series in which 203 subjects with primary angle closure or open angles were recruited. Images of the nasal, temporal and inferior angles were obtained with AS-OCT in dark conditions. Subjects then underwent gonioscopy by an independent examiner who was masked to the AS-OCT findings. PAS were identified by gonioscopy and defined as abnormal adhesions of the iris to the angle that were at least half a clock hour in width and present to the level of the anterior trabecular meshwork or higher. The total clock hours of PAS were recorded. Sixty-eight subjects (33.5%) were PACS, 76 subjects (37.4%) had PAC/PACG, 14 (6.9%) had primary open angle glaucoma, and 45 (22.2%) subjects were normal with open angles. There was a weak but significant correlation between the angle opening distance (AOD), trabecular iris space area (TISA) and angle recess area (ARA) with clock hours of PAS (Spearman's correlation coefficients = -0.30, -0.32 and -0.32, respectively, p<0.001). The mean values of the AOD, TISA and ARA in the nasal, temporal and inferior quadrants were significantly less in eyes with PAS compared with those without (p<0.001, Mann-Whitney U test). Analysis by quadrant showed that these parameters were smaller in the nasal and temporal quadrants in eyes with PAS (p<0.01). Angle width determined by AS-OCT and the extent of PAS were weakly correlated, and angle width was significantly smaller in eyes with PAS.


Binocular and monocular depth cues in online feedback control of 3D pointing movement.
Previous work has shown that humans continuously use visual feedback of the hand to control goal-directed movements online. In most studies, visual error signals were predominantly in the image plane and, thus, were available in an observer's retinal image. We investigate how humans use visual feedback about finger depth provided by binocular and monocular depth cues to control pointing movements. When binocularly viewing a scene in which the hand movement was made in free space, subjects were about 60 ms slower in responding to perturbations in depth than in the image plane. When monocularly viewing a scene designed to maximize the available monocular cues to finger depth (motion, changing size, and cast shadows), subjects showed no response to perturbations in depth. Thus, binocular cues from the finger are critical to effective online control of hand movements in depth. An optimal feedback controller that takes into account the low peripheral stereoacuity and inherent ambiguity in cast shadows can explain the difference in response time in the binocular conditions and lack of response in monocular conditions.


Genome-scale design of PCR primers and long oligomers for DNA microarrays.
During the last years, the demand for custom-made cDNA chips/arrays as well as whole genome chips is increasing rapidly. The efficient selection of gene-specific primers/oligomers is of the utmost importance for the successful production of such chips. We developed GenomePRIDE, a highly flexible and scalable software for designing primers/oligomers for large-scale projects. The program is able to generate either long oligomers (40-70 bases), or PCR primers for the amplification of gene-specific DNA fragments of user-defined length. Additionally, primers can be designed in-frame in order to facilitate large-scale cloning into expression vectors. Furthermore, GenomePRIDE can be adapted to specific applications such as the generation of genomic amplicon arrays or the design of fragments specific for alternative splice isoforms. We tested the performance of GenomePRIDE on the entire genomes of Listeria monocytogenes (1584 gene-specific PCRs, 48 long oligomers) as well as of eukaryotes such as Schizosaccharomyces pombe (5006 gene-specific PCRs), and Drosophila melanogaster (21 306 gene-specific PCRs). With its computing speed of 1000 primer pairs per hour and a PCR amplification success of 99%, GenomePRIDE represents an extremely cost- and time-effective program.


Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL/6J mice.
Type 2 diabetes is associated with obesity, ectopic lipid accumulation and low-grade inflammation. A dysfunctional gut microbiota has been suggested to participate in the pathogenesis of the disease. Green tea is rich in polyphenols and has previously been shown to exert beneficial metabolic effects. Lactobacillus plantarum has the ability to metabolize phenolic acids. The health promoting effect of whole green tea powder as a prebiotic compound has not been thoroughly investigated previously. C57BL/6J mice were fed a high-fat diet with or without a supplement of 4% green tea powder (GT), and offered drinking water supplemented with Lactobacillus plantarum DSM 15313 (Lp) or the combination of both (Lp + GT) for 22 weeks. Parameters related to obesity, glucose tolerance, lipid metabolism, hepatic steatosis and inflammation were examined. Small intestinal tissue and caecal content were collected for bacterial analysis. Mice in the Lp + GT group had significantly more Lactobacillus and higher diversity of bacteria in the intestine compared to both mice in the control and the GT group. Green tea strongly reduced the body fat content and hepatic triacylglycerol and cholesterol accumulation. The reduction was negatively correlated to the amount of Akkermansia and/or the total amount of bacteria in the small intestine. Markers of inflammation were reduced in the Lp + GT group compared to control. PLS analysis of correlations between the microbiota and the metabolic variables of the individual mice showed that relatively few components of the microbiota had high impact on the correlation model. Green tea powder in combination with a single strain of Lactobacillus plantarum was able to promote growth of Lactobacillus in the intestine and to attenuate high fat diet-induced inflammation. In addition, a component of the microbiota, Akkermansia, correlated negatively with several metabolic parameters known to be risk factors for the development of type 2 diabetes.


Xanthusbase after five years expands to become Openmods.
Xanthusbase (http://www.xanthusbase.org), a model organism database for the bacterium Myxococcus xanthus, functions as a collaborative information repository based on Wikipedia principles. It was created more than 5 years ago to serve as a cost-effective reference database for M. xanthus researchers, an education tool for undergraduate students to learn about genome annotation, and a means for the community of researchers to collaboratively improve their organism's annotation. We have achieved several goals and are seeking creative solutions to ongoing challenges. Along the way we have made several important improvements to Xanthusbase related to stability, security and usability. Most importantly, we have designed and implemented an installer that enables other microbial model organism communities to use it as a MOD. This version, called Openmods, has already been used to create Xenorhabdusbase (http://xenorhabdusbase.bact.wisc.edu), Caulobacterbase (http://caulobacterbase.bsd.uchicago.edu) and soon Bdellovibriobase.


Beverage Consumption Patterns among Infants and Young Children (0⁻47.9 Months): Data from the Feeding Infants and Toddlers Study, 2016.
(1) Background: Data about early life beverage intake patterns is sparse. We describe beverage patterns among infants and young children from the Feeding Infants and Toddlers Study (FITS) 2016. (2) Methods: FITS 2016 is a cross-sectional survey of U.S. parents/caregivers of children 0⁻47.9 months (n = 3235). Food and beverage intakes were collected by 24-h dietary recalls to describe beverage consumption patterns including: a) prevalence of consumption, per capita and per consumer intake, b) contribution to intake of calories and key nutrients, and c) prevalence according to eating occasions. (3) Results: Breast milk and infant formula were commonly consumed among <12-month-olds. Among 12⁻23.9-month-olds, the most commonly consumed beverage was whole milk (67% consuming), followed by 100% juice (50% consuming). Plain drinking water was consumed by 70% of 12⁻23.9-month-olds and 78% of 24⁻47.9-month-olds. Among 12⁻47.9-month-olds, milks provided more energy and key nutrients than all other beverages. Across eating occasions, sugar-sweetened beverage (SSB) consumption, especially in the form of fruit-flavored drinks, was higher among 24⁻47.9 compared to 12⁻23.9-month-olds. Only 23⁻32% of ≥12-month-olds consumed milk or water at lunch or dinner. (4) Conclusions: Opportunities exist to improve beverage patterns. Future interventions may benefit from focusing on timely introduction of age-appropriate beverages and reducing consumption of SSBs.


Bioethics and transnational medical travel: India,"medical tourism," and the globalisation of healthcare.
Health-related travel, also referred to as "medical tourism" is historically well-known. Its emerging contemporary form suggests the development of a form of globalised for-profit healthcare. Medical tourism to India, the focus of a recent conference in Canada, provides an example of the globalisation of healthcare. By positioning itself as a low-cost, high-tech, fast-access and high-quality healthcare destination country, India offers healthcare to medical travellers who are frustrated with waiting lists and the limited availability of some procedures in Canada. Although patients have the right to travel and seek care at international medical facilities, there are a number of dimensions of medical tourism that are disturbing. The diversion of public investments in healthcare to the private sector, in order to serve medical travellers, perversely transfers public resources to international patients at a time when the Indian public healthcare system fails to provide primary healthcare to its own citizens. Further, little is known about patient safety and quality care in transnational medical travel. Countries that are departure points as well as destination countries need to carefully explore the ethical, social, cultural, and economic consequences of the growing phenomenon of for-profit international medical travel.


The cellular origin of corticofugal projections to the superior olivary complex in the rat.
Corticofugal pathways originating in auditory cortex innervate most subcortical auditory nuclei in the ascending pathway [Auditory Neurosci. 1 (1995) 287-308; J. Comp. Neurol. 371 (1996) 15-40]. Our goal is to determine if these projections arise from the same neurons or if different neurons project to each of the separate structures. We also seek to identify the layers and fields of auditory cortex from which these neurons originate. In the present study, we answer these questions with respect to the projections to the superior olivary complex (SOC). Fluorescent retrograde tracers, Fast Blue (FB) or Diamidino Yellow (DiY), were injected into the SOC and the pattern of labeled cells was determined in temporal neocortex. We also injected FB into the granule cell domain (GCD) of the cochlear nucleus. Cortical projections to the GCD derive exclusively from layer V pyramidal cells in primary auditory cortex [Brain Res. 706 (1996) 97-102]. Thus the pattern of labeling produced by injections in the GCD provided a reference for interpreting the labeling after SOC injections. Layer V pyramidal cells project to the SOC, and these neurons were distributed bilaterally in primary and secondary areas of auditory cortex. The projections to the SOC from primary auditory cortex are predominantly uncrossed, whereas those from secondary auditory cortex are nearly equal for the two hemispheres. In animals that received injections of FB in the GCD and DiY in the SOC, cells labeled by each injection had a different laminar distribution and very few cells were double labeled. These data suggest that the cortical pathways ending in the cochlear nucleus and SOC are largely independent. We discuss the implications of these findings with respect to the multifunctional nature of the SOC in brainstem auditory processing.


Emily Dickinson revisited: a study of periodicity in her work.
Emily Dickinson, arguably one of America's foremost poets, is characterized by critics as able to capture extreme emotional states in her greatest work. Recent dating of her poems offers the periodicity of her writing as a behavior that can be examined for patterns of affective illness that may relate to these states. The bulk of Dickinson's work was written during a clearly defined 8-year period when she was age 28-35. Poems written during that period, 1858-1865, were grouped by year and examined for annual and seasonal distribution. Her 8-year period of productivity was marked by two 4-year phases. The first shows a seasonal pattern characterized by greater creative output in spring and summer and a lesser output during the fall and winter. This pattern was interrupted by an emotional crisis that marked the beginning of the second phase, a 4-year sustained period of greatly heightened productivity and the emergence of a revolutionary poetic style. These data, supported by excerpts from letters to friends during this period of Dickinson's life, demonstrate seasonal changes in mood during the first four years of major productivity, followed by a sustained elevation of creative energy, mood, and cognition during the second. They suggest, as supported by family history, a bipolar pattern previously described in creative artists.


The University of New Hampshire's Young Adult Health Risk Screening Initiative.
Few comprehensive studies exist that evaluate the nutrient intake and health indicators of college-aged students. This article describes the University of New Hampshire's Young Adult Health Risk Screening Initiative and examines results from participants evaluated from September 2005 through July 2007. This cross-sectional study included 1,701 students who enrolled in an introductory nutrition course, met age requirements (18 to 24 years), agreed to participate, and completed related assessments. All evaluation components were built into the semester-long course design, thus minimizing participant burden. Anthropometric measurements, blood lipids, blood glucose, and blood pressure were measured directly by research staff. Online dietary intake was self-reported and evaluated using a software program. Health risk data indicate high rates of overweight (33%), elevated low-density lipoprotein cholesterol (53%), and elevated systolic (47%) and diastolic blood pressures (39%). Less than 30 minutes of physical activity per day was reported by 28% of respondents. The majority of males (94%) and females (73%) exceeded sodium guidelines. Although females were less likely to be overweight than males, few met recommended intakes for vitamin D (26%), calcium (25%), potassium (35%), iron (31%), and folate (32%). Undergraduate and graduate dietetics students assisted with biological assessments, data entry, and record maintenance. Data inclusion rates ranged between 84% and 94% for various measurements. The methods employed in this study could be modified by institutions interested in profiling the health status of students. Results have led to an enhanced understanding of the nutrition practices and health status of this population and will serve to inform university programs and policies.


Modulation of Polycystic Kidney Disease Severity by Phosphodiesterase 1 and 3 Subfamilies.
Aberrant intracellular calcium levels and increased cAMP signaling contribute to the development of polycystic kidney disease (PKD). cAMP can be hydrolyzed by various phosphodiesterases (PDEs). To examine the role of cAMP hydrolysis and the most relevant PDEs in the pathogenesis of PKD, we examined cyst development in Pde1- or Pde3-knockout mice on the Pkd2(-/WS25) background (WS25 is an unstable Pkd2 allele). These PDEs were selected because of their importance in cross-talk between calcium and cyclic nucleotide signaling (PDE1), control of cell proliferation and cystic fibrosis transmembrane conductance regulator (CFTR) -driven fluid secretion (PDE3), and response to vasopressin V2 receptor activation (both). In Pkd2(-/WS25) mice, knockout of Pde1a, Pde1c, or Pde3a but not of Pde1b or Pde3b aggravated the development of PKD and was associated with higher levels of protein kinase A-phosphorylated (Ser133) cAMP-responsive binding protein (P-CREB), activating transcription factor-1, and CREB-induced CRE modulator proteins in kidney nuclear preparations. Immunostaining also revealed higher expression of P-CREB in Pkd2(-/) (WS25);Pde1a(-/-), Pkd2(-) (/WS25);Pde1c(-/-), and Pkd2(-/) (WS25);Pde3a(-/-) kidneys. The cystogenic effect of desmopressin administration was markedly enhanced in Pkd2(-/WS25);Pde3a(-/-) mice, despite PDE3 accounting for only a small fraction of renal cAMP PDE activity. These observations show that calcium- and calmodulin-dependent PDEs (PDE1A and PDE1C) and PDE3A modulate the development of PKD, possibly through the regulation of compartmentalized cAMP pools that control cell proliferation and CFTR-driven fluid secretion. Treatments capable of increasing the expression or activity of these PDEs may, therefore, retard the development of PKD.


Evidence of multiple chromosomal inversions in Aedes aegypti formosus from Senegal.
Chromosomal inversions are prevalent in mosquito species but polytene chromosomes are difficult to prepare and visualize in members of the tribe Aedinii and thus there exists only indirect evidence of inversions. We constructed an F(1) intercross family using a P(1) female from a laboratory strain of Aedes aegypti aegypti (Aaa) and a P(1) male Aedes aegypti formosus (Aaf) from a strain collected from south-eastern Senegal. Recombination rates in the F(2) offspring were severely reduced and genotype ratios suggested a deleterious recessive allele on chromosome 3. The F(2) linkage map was incongruent in most respects with the established map for Aaa. Furthermore, no increased recombination was detected in F(5) offspring. Recombination rates and gene order were consistent with the presence in Aaf of at least four large inversions on chromosome 1, a single small inversion on chromosome 2 and three inversions on chromosome 3.


Discovery of new microRNAs by small RNAome deep sequencing in childhood acute lymphoblastic leukemia.
MicroRNAs (miRNAs) relevant to acute lymphoblastic leukemia (ALL) in children are hypothesized to be largely unknown as most miRNAs have been identified in non-leukemic tissues. In order to discover these miRNAs, we applied high-throughput sequencing to pooled fractions of leukemic cells obtained from 89 pediatric cases covering seven well-defined genetic types of ALL and normal hematopoietic cells. This resulted into 78 million small RNA reads representing 554 known, 28 novel and 431 candidate novel miR genes. In all, 153 known, 16 novel and 170 candidate novel mature miRNAs and miRNA-star strands were only expressed in ALL, whereas 140 known, 2 novel and 82 candidate novel mature miRNAs and miRNA-star strands were unique to normal hematopoietic cells. Stem-loop reverse transcriptase (RT)-quantitative PCR analyses confirmed the differential expression of selected mature miRNAs in ALL types and normal cells. Expression of 14 new miRNAs inversely correlated with expression of predicted target genes (-0.49 ≤ Spearman's correlation coefficients (Rs)≤ -0.27, P ≤ 0.05); among others, low levels of novel sol-miR-23 associated with high levels of its predicted (antiapoptotic) target BCL2 (B-cell lymphoma 2) in precursor B-ALL (Rs -0.36, P = 0.007). The identification of >1000 miR genes expressed in different types of ALL forms a comprehensive repository for further functional studies that address the role of miRNAs in the biology of ALL.