The multiscale top-hat tensor enables specific enhancement of curvilinear structures in 2D and 3D images.
Quantification and modelling of curvilinear structures in 2D and 3D images is a common challenge in a wide range of biomedical applications. Image enhancement is a crucial pre-processing step for curvilinear structure quantification. Many of the existing state-of-the-art enhancement approaches still suffer from contrast variations and noise. In this paper, we propose to address such problems via the use of a multiscale image processing approach, called Multiscale Top-Hat Tensor (MTHT). MTHT produces a better quality enhancement of curvilinear structures in low contrast and noisy images compared with other approaches in a range of 2D and 3D biomedical images. The proposed approach combines multiscale morphological filtering with a local tensor representation of curvilinear structure. The MTHT approach is validated on 2D and 3D synthetic and real images, and is also compared to the state-of-the-art curvilinear structure enhancement approaches. The obtained results demonstrate that the proposed approach provides high-quality curvilinear structure enhancement, allowing high accuracy segmentation and quantification in a wide range of 2D and 3D image datasets.


Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis.
Metastatic breast cancer (BC) (also referred to as stage IV) spreads beyond the breast to the bones, lungs, liver, or brain and is a major contributor to the deaths of cancer patients. Interestingly, metastasis is a result of stroma-coordinated hallmarks such as invasion and migration of the tumor cells from the primary niche, regrowth of the invading tumor cells in the distant organs, proliferation, vascularization, and immune suppression. Targeted therapies, when used as monotherapies or combination therapies, have shown limited success in decreasing the established metastatic growth and improving survival. Thus, novel therapeutic targets are warranted to improve the metastasis outcomes. We have been actively investigating the cytochrome P450 4 (CYP4) family of enzymes that can biosynthesize 20-hydroxyeicosatetraenoic acid (20-HETE), an important signaling eicosanoid involved in the regulation of vascular tone and angiogenesis. We have shown that 20-HETE can activate several intracellular protein kinases, pro-inflammatory mediators, and chemokines in cancer. This review article is focused on understanding the role of the arachidonic acid metabolic pathway in BC metastasis with an emphasis on 20-HETE as a novel therapeutic target to decrease BC metastasis. We have discussed all the significant investigational mechanisms and put forward studies showing how 20-HETE can promote angiogenesis and metastasis, and how its inhibition could affect the metastatic niches. Potential adjuvant therapies targeting the tumor microenvironment showing anti-tumor properties against BC and its lung metastasis are discussed at the end. This review will highlight the importance of exploring tumor-inherent and stromal-inherent metabolic pathways in the development of novel therapeutics for treating BC metastasis.


Preventing progression of allergic rhinitis: the role of specific immunotherapy.
Allergic rhinitis and asthma are examples of allergic airways disease. Despite their differing symptomatology, both disorders affect the mucosal lining of the respiratory tract and are linked by common underlying cellular processes, thus, using the 'united airways' approach, they can be considered part of the same allergic disease. The conditions are often comorbid, and there is evidence to suggest that allergic rhinitis in children is a significant risk factor for subsequent development of asthma. Management strategies that target the underlying cause of allergic rhinitis in children have the potential to offer additional symptom control above that of symptomatic medications, and prevent disease progression. Specific immunotherapy (SIT) is the only currently available treatment that is proven to target the disease in this way. SIT affects the underlying cause of allergic rhinitis, producing changes in antibody responses to allergens. It has been shown to be effective in the reduction of allergic rhinitis symptoms in both children and adults, with effects being sustained for several years after treatment completion. Furthermore, a number of trials provide evidence that SIT may prevent the development of new sensitisations and asthma in children and adults with allergic rhinitis. One such open-label, randomised controlled study in children/adolescents (the Preventive Allergy Treatment Study) showed that significantly fewer patients who received 3 years of SIT for grass/birch pollen-induced allergic rhinitis had developed asthma 10 years after treatment initiation versus controls. Some clinical guidelines acknowledge this potential asthma preventive effect in children and the need for additional data from double-blind, placebo-controlled trials to support these findings.


Aneuploidy and isochromosome formation in drug-resistant Candida albicans.
Resistance to the limited number of available antifungal drugs is a serious problem in the treatment of Candida albicans. We found that aneuploidy in general and a specific segmental aneuploidy, consisting of an isochromosome composed of the two left arms of chromosome 5, were associated with azole resistance. The isochromosome forms around a single centromere flanked by an inverted repeat and was found as an independent chromosome or fused at the telomere to a full-length homolog of chromosome 5. Increases and decreases in drug resistance were strongly associated with gain and loss of this isochromosome, which bears genes expressing the enzyme in the ergosterol pathway targeted by azole drugs, efflux pumps, and a transcription factor that positively regulates a subset of efflux pump genes.


Recurrent tissue-specific mtDNA mutations are common in humans.
Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in two additional individuals. These recurrent mutations all occur within or in very close proximity to sites that regulate mtDNA replication, strongly implying that these variations alter the replication dynamics of the mutated mtDNA genome. These recurrent variants are all independent of each other and do not occur in the mtDNA coding regions. The most parsimonious explanation of the data is that these frequently repeated mutations experience tissue-specific positive selection, probably through replication advantage.


The future of academic haematology.
Recent advances in the basic medical sciences, particularly cell biology and genomics, have great promise for the future development of all aspects of haematological practice. They will also impinge on the hitherto neglected fields of haematology, including haematology involving the care of the rapidly increasing number of elderly patients and the complex problems of haematological practice in the developing countries. To obtain the maximum benefit from these new developments it will be necessary to review the patterns of training of haematologists of the future at every level. In short, it will be important to try to design and develop various career pathways for training haematologists including those who wish to work full time in basic research, combine research with clinical practice, or commit all their time to clinical work and teaching.


Low bone mass in Pompe disease: muscular strength as a predictor of bone mineral density.
Pompe disease is an inherited metabolic myopathy caused by deficiency of acid alpha-glucosidase. The introduction of enzyme replacement therapy as treatment for the disease may change prospects for patients and may require that more attention be paid to co-morbidities such as osteoporosis. Bone mineral status was assessed in children and adults with Pompe disease and compared with reference values by means of dual energy X-ray absorptiometry (DXA) technology (GE Lunar DPX, GE Health Care). Bone mineral density (BMD) of the total body and the lumbar spine (L2-L4) was measured in adults and children; BMD of the femoral neck was measured in adults only. Exclusion criteria were: age<4 years, severe contractures, and inability to transfer the patient. 46 patients were enrolled in the study; 36 adults and 10 children. The BMD was significantly lower in Pompe patients than in healthy individuals. Sixty-seven percent of patients had a BMD Z-score below -1, 26% were classified as osteoporosis/low bone mass for chronological age (T-score<-2.5 in adults or Z-score<-2 in children), 66% had a BMD Z-score below -1 of the femoral neck, and 34% had a BMD Z-score below -1 for the lumbar spine. Osteoporosis/low bone mass for chronological age was more frequent in patients who were wheelchair-bound, but was also observed in ambulant patients. We found a significant correlation between proximal muscle strength and total body BMD. Of the 10 children, 8 (all four patients with the classic infantile form) had a low BMD. Low BMD is a frequent finding in patients with Pompe disease and may be causally related to decreased proximal muscle strength. BMD should be monitored at regular intervals. Children deserve specific attention.


The identification and functional characterization of WxL proteins from Enterococcus faecium reveal surface proteins involved in extracellular matrix interactions.
The WxL domain recently has been identified as a novel cell wall binding domain found in numerous predicted proteins within multiple Gram-positive bacterial species. However, little is known about the function of proteins containing this novel domain. Here, we identify and characterize 6 Enterococcus faecium proteins containing the WxL domain which, by reverse transcription-PCR (RT-PCR) and genomic analyses, are located in three similarly organized operons, deemed WxL loci A, B, and C. Western blotting, electron microscopy, and enzyme-linked immunosorbent assays (ELISAs) determined that genes of WxL loci A and C encode antigenic, cell surface proteins exposed at higher levels in clinical isolates than in commensal isolates. Secondary structural analyses of locus A recombinant WxL domain-containing proteins found they are rich in β-sheet structure and disordered segments. Using Biacore analyses, we discovered that recombinant WxL proteins from locus A bind human extracellular matrix proteins, specifically type I collagen and fibronectin. Proteins encoded by locus A also were found to bind to each other, suggesting a novel cell surface complex. Furthermore, bile salt survival assays and animal models using a mutant from which all three WxL loci were deleted revealed the involvement of WxL operons in bile salt stress and endocarditis pathogenesis. In summary, these studies extend our understanding of proteins containing the WxL domain and their potential impact on colonization and virulence in E. faecium and possibly other Gram-positive bacterial species.


Investigating the role played by social support in the association between religiosity and mental health in low income older adults: results from the São Paulo Ageing & Health Study (SPAH).
Religiosity has been associated with mental health, especially in the elderly. There is a shortage of studies on the factors that mediate this association, including social support. The aim of this study was to assess the association between the various dimensions of religiosity and the prevalence of common mental disorders among the elderly, and to verify whether social support can work as a mechanism that explains such mediation. The sample consisted of an elderly population living in a low income region of the city of São Paulo (N = 1,980). Data on the socio-demographic profile of this population and on the prevalence of common mental disorders were collected, and indicators of religiosity and social support were identified. 90.7% of the sample considered themselves to be religious. In terms of denomination, 66.6% were Catholic. Forty-one per cent attended some kind of religious activity at least once or more times a week. The presence of common mental disorders was not associated with religious affiliation or subjective religiosity. The prevalence of common mental disorders in followers attending religious services was approximately half (OR between 0.43 and 0.55, p < 0.001) compared to those who never attend a religious service. Attending religious services was associated with higher levels of social support. The association between a higher attendance frequency and fewer common mental disorders did not change after the inclusion of relevant of social support variables. The study showed that subjects presented high levels of religiosity and that there is a strong association between religious attendance and the prevalence of common mental disorders, which could not be explained by social support.


Regeneration in the Xenopus tadpole optic nerve is preceded by a massive macrophage/microglial response.
Changes in the optic nerve following a crush lesion and during axonal regeneration have been studied in Xenopus tadpoles, using ultrastructural and immunohistological methods. Degeneration of both unmyelinated and myelinated axons is very rapid and leads to the formation, within 5 days, of a nerve which consists largely of degeneration debris and cells. Immunohistological analysis with monoclonal antibody 5F4 shows that there is a rapid and extensive microglial/macrophage response to crush of the nerve. Regenerating axons have begun to enter the distal stump by 5 days and grow along the outer part of the nerve in close approximation to the astrocytic glia limitans. Between 5 and 10 days after nerve crush, regenerating axons reach and pass the chiasma. Macrophages are seen in the nerve at the site of the lesion within 1 h, and the response peaks between 3-5 days, just before axonal regeneration gets under way.


Observer biases in the 3D interpretation of line drawings.
Line drawings produced by contours traced on a surface can produce a vivid impression of the surface shape. The stability of this perception is notable considering that the information provided by the surface contours is quite ambiguous. We have studied the stability of line drawing perception from psychophysical and computational standpoints. For a given family of simple line drawings, human observers could perceive the drawings as depicting either an elliptic (egg-shaped) or hyperbolic (saddle-shaped) smooth surface patch. Rotation of the image along the line of sight and change in aspect ratio of the line drawing could bias the observer toward either interpretation. The results were modeled by a simple Bayesian observer that computes the probability to choose either interpretation given the information in the image and prior preferences. The model's decision rule is noncommitting: for a given input image its responses are still probabilistic, reflecting variability in the modeled observers' judgements. A good fit to the data was obtained when three observer assumptions were introduced: a preference for convex surfaces, a preference for surface contours aligned with the principal lines of curvature, and a preference for a surface orientation consistent with an object viewed from above. We discuss how these assumptions might reflect regularities of the visual world.


Investigation of ultrasonic properties of PAG and MAGIC polymer gel dosimeters.
Ultrasonic speed of propagation and attenuation were investigated as a function of absorbed radiation dose in PAG and MAGIC polymer gel dosimeters. Both PAG and MAGIC gel dosimeters displayed a dependence of ultrasonic parameters on absorbed dose with attenuation displaying significant changes in the dose range investigated. The ultrasonic attenuation dose sensitivity at 4 MHz in MAGIC gels was determined to be 4.7 +/- 0.3 dB m(-1) Gy(-1) and for PAG 3.9 +/- 0.3 dB m(-1) Gy(-1). Ultrasonic speed dose sensitivities were 0.178 +/- 0.006 m s(-1) Gy(-1) for MAGIC gel and -0.44 +/- 0.02 m s(-1) Gy(-1) for PAG. Density and compressional elastic modulus were investigated to explain the different sensitivities of ultrasonic speed to radiation for PAG and MAGIC gels. The different sensitivities were found to be due to differences in the compressional elastic modulus as a function of dose for the two formulations. To understand the physical phenomena underlying the increase in ultrasonic attenuation with dose, the viscoelastic properties of the gels were studied. Results suggest that at ultrasonic frequencies, attenuation in polymer gel dosimeters is primarily due to volume viscosity. It is concluded that ultrasonic attenuation significantly increases with absorbed dose. Also, the ultrasonic speed in polymer gel dosimeters is affected by changes in dosimeter elastic modulus that are likely to be a result of polymerization. It is suggested that ultrasound is a sufficiently sensitive technique for polymer gel dosimetry.


The Effects of Caffeine on Voice: A Systematic Review.
Caffeine is considered a dehydrating agent due to its diuretic effects and influences the body's fluid balance. The relationship between voice and hydration has been widely investigated and it is accepted that inadequate hydration has detrimental effects on phonation. Since dehydration negatively affects the vocal folds and caffeine is considered a dehydrating agent, it can be hypothesized that voice might be negatively affected by caffeine intake. This systematic review aims to summarize and appraise the available evidence regarding the effects of caffeine on voice. Randomized and non-randomized experimental studies of healthy participants were retrieved following an electronic searching of six databases in June 2020. No publication, language or date restrictions were applied. Data extraction of relevant data and risk of bias assessment was conducted independently by two reviewers. Five non-randomized experimental studies were deemed eligible for inclusion. The format of the administered interventions in the included studies was either liquid (coffee) or solid (caffeine tablets). Reported outcome measures used to examine the effects of caffeine on phonation consisted of acoustic, aerodynamic and (auditory & self-) perceptual. No measures were adversely affected by caffeine consumption. Clinicians commonly advise patients to refrain from caffeine, as caffeine intake increases diuresis with subsequent effects on fluid balance. Such imbalances can potentially induce dehydration which can be detrimental to phonation. This notion cannot be supported empirically, as the evidence is deemed unreliable and no firm conclusions can be elicited to guide clinical practice. The results of this review demonstrate the lack of research in the field and the necessity for future investigations in order to inform evidence-based practice through reliable and valid outcomes.


Phospholipase D-mediated activation of IQGAP1 through Rac1 regulates hyperoxia-induced p47phox translocation and reactive oxygen species generation in lung endothelial cells.
Phosphatidic acid generated by the activation of phospholipase D (PLD) functions as a second messenger and plays a vital role in cell signaling. Here we demonstrate that PLD-dependent generation of phosphatidic acid is critical for Rac1/IQGAP1 signal transduction, translocation of p47(phox) to cell periphery, and ROS production. Exposure of [(32)P]orthophosphate-labeled human pulmonary artery endothelial cells (HPAECs) to hyperoxia (95% O(2) and 5% CO(2)) in the presence of 0.05% 1-butanol, but not tertiary-butanol, stimulated PLD as evidenced by accumulation of [(32)P]phosphatidylbutanol. Infection of HPAECs with adenoviral constructs of PLD1 and PLD2 wild-type potentiated hyperoxia-induced PLD activation and accumulation of O(2)(.)/reactive oxygen species (ROS). Conversely, overexpression of catalytically inactive mutants of PLD (hPLD1-K898R or mPLD2-K758R) or down-regulation of expression of PLD with PLD1 or PLD2 siRNA did not augment hyperoxia-induced [(32)P]phosphatidylbutanol accumulation and ROS generation. Hyperoxia caused rapid activation and redistribution of Rac1, and IQGAP1 to cell periphery, and down-regulation of Rac1, and IQGAP1 attenuated hyperoxia-induced tyrosine phosphorylation of Src and cortactin and ROS generation. Further, hyperoxia-mediated redistribution of Rac1, and IQGAP1 to membrane ruffles, was attenuated by PLD1 or PLD2 small interference RNA, suggesting that PLD is upstream of the Rac1/IQGAP1 signaling cascade. Finally, small interference RNA for PLD1 or PLD2 attenuated hyperoxia-induced cortactin tyrosine phosphorylation and abolished Src, cortactin, and p47(phox) redistribution to cell periphery. These results demonstrate a role of PLD in hyperoxia-mediated IQGAP1 activation through Rac1 in tyrosine phosphorylation of Src and cortactin, as well as in p47(phox) translocation and ROS formation in human lung endothelial cells.


Are you doing what you want to do? Leisure preferences of adolescents with cerebral palsy.
This study aimed at describing leisure activity preferences of adolescents with cerebral palsy (CP) and their relationship to participation and to identify factors associated with greater interest in particular leisure activities. A cross-sectional design was used. Participants were adolescents (n = 127; 59.5% male; ages 12-19 years old; mean = 15.3; SD = 2.01 years) with CP (GMFCS levels: I 40%, II 33%, III-IV 26%), who could complete the Preferences for Activities of Children (PAC) and other self-report questionnaires. Social (2.53; 0.38) and active-physical activities were most preferred (2.10; 0.42), and self-improvement activities were least preferred (1.93; 0.49). Preference for certain activities was not strongly associated with actual involvement in these activities. Family activity-orientation, family expressiveness, and adolescent's motivation explained 15% of the variance in preferences for social activities, and 37% of the variance in preferences for self-improvement activities. Family factors, personal factors, and functional abilities influence leisure preferences. Rehabilitation interventions should consider adolescents' preferences and family dynamics to promote leisure participation.


Past experiences, current realities and future possibilities for HIV nursing education and care in Canada.
Nurses may have inadequate basic education and opportunities for continuing education in relation to HIV care. As well nurses may perpetuate and impose stigma. We developed, implemented and evaluated an educational intervention to reduce stigma and discrimination among nurses providing HIV care. The intervention used a mentorship model that brought experienced nurses in HIV care and people living with HIV together with nurses who wanted to learn more about HIV nursing care. We examined our findings in relation to past experiences, current realities and future possibilities for HIV nursing education and care in Canada. Our findings demonstrated that many nurses were interested in improving their HIV care, yet few opportunities existed for them to do so. We found that HIV nursing education and expertise were significantly different among participants and across clinical sites. This difference was visible in basic education, services offered for HIV and AIDS care, the collaborative and inter-professional nature of care, and opportunities for continuing education. Mentorship education is an effective strategy to not only address a critical void in knowledge, but also to promote a fundamental shift in attitudes. With the recent call by the World Health Organization to place nurses in key positions to provide HIV care, treatment and prevention, it is imperative to prepare nurses at both the undergraduate and graduate level, as well as those in practice, to fulfill this call.


rhomboid and Star interact synergistically to promote EGFR/MAPK signaling during Drosophila wing vein development.
Genes of the ventrolateral group in Drosophila are dedicated to developmental regulation of Egfr signaling in multiple processes including wing vein development. Among these genes, Egfr encodes the Drosophila EGF-Receptor, spitz (spi) and vein (vn) encode EGF-related ligands, and rhomboid (rho) and Star (S) encode membrane proteins. In this study, we show that rho-mediated hyperactivation of the EGFR/MAPK pathway is required for vein formation throughout late larval and early pupal development. Consistent with this observation, rho activity is necessary and sufficient to activate MAPK in vein primordium during late larval and early pupal stages. Epistasis studies using a dominant negative version of Egfr and a ligand-independent activated form of Egfr suggest that rho acts upstream of the receptor. We show that rho and S function in a common aspect of vein development since loss-of-function clones of rho or S result in nearly identical non-autonomous loss-of-vein phenotypes. Furthermore, mis-expression of rho and S in wild-type and mutant backgrounds reveals that these genes function in a synergistic and co-dependent manner. In contrast, spi does not play an essential role in the wing. These data indicate that rho and S act in concert, but independently of spi, to promote vein development through the EGFR/MAPK signaling pathway.


Neither ideologues nor agnostics: alternative voters' belief system in an age of partisan politics.
How do Americans organize their political beliefs? This article argues that party polarization and the growing prominence of moral issues in recent decades have catalyzed different responses by different groups of Americans. The article investigates systematic heterogeneity in the organization of political attitudes using relational class analysis, a graph-based method for detecting multiple patterns of opinion in survey data. Three subpopulations, each characterized by a distinctive way of organizing its political beliefs, are identified: ideologues, whose political attitudes strongly align with either liberal or conservative categories; alternatives, who are instead morally conservative but economically liberal, or vice versa; and agnostics, who exhibit weak associations between political beliefs. Individuals' sociodemographic profiles, particularly their income, education, and religiosity, lie at the core of the different ways in which they understand politics. Results show that while ideologues have gone through a process of issue alignment, alternatives have grown increasingly apart from the political agendas of both parties. The conflictual presence of conservative and liberal preferences has often been resolved by alternative voters in favor of the Republican Party.


Neonatal anesthesia exposure impacts brain microRNAs and their associated neurodevelopmental processes.
MicroRNAs (miRNAs), when subjected to environmental stimuli, can exhibit differential expression. As critical regulators of gene expression, differential miRNA expression has been implicated in numerous disorders of the nervous system. In this study, we focused on the effect of a general anesthetic, as an environmental stimulus, on miRNA expression of the developing brain. General anesthetics have potential long-lasting neurotoxic effects on the developing brain, resulting in behavioral changes in adulthood. We first carried out an unbiased profiling approach to examine the effect of single-episode neonatal general anesthetic, sevoflurance (sevo), exposure on miRNA expression of the brain. Neonatal sevo has a significant effect on the expression of specific miRNAs of the whole brain and the hippocampus that is both immediate - directly after neonatal treatment, as well as long-lasting - during adulthood. Functionally, neonatal sevo-associated miRNA gene-targets share potential neurodevelopmental pathways related to axon guidance, DNA transcription, protein phosphorylation and nervous system development. Our understanding on the role of miRNAs provides a putative epigenetic/molecular bridge that links neonatal general anesthetic's effect with its associated functional change.


Patient-reported symptoms and diagnostic journey in Multiple Myeloma.
Late presentation of multiple myeloma (MM) heightens the risk of complication risks, including end-organ damage. This study aimed to: 1) detail the diagnostic journey of MM patients, encompassing symptoms, initial diagnoses, and healthcare professionals met; 2) establish the median duration from symptom onset to MM diagnosis; and 3) examine factors linked to timely MM diagnosis within 12 weeks. A total of 300 adults self-reporting MM were analysed from the Rare and Undiagnosed Diseases cohort Study (RUDY). The RUDY study is a web-based platform, where participants provide dynamic consent and self-report their MM diagnosis and information about their diagnostic journey. This includes the estimated date of initial potential first symptoms, descriptions of these symptoms, the healthcare professionals they consulted, and other diagnoses received before the MM diagnosis. Descriptive statistics, combinatorial analyses and logistic regression analyses were used to describe and examine the diagnostic journey of individuals with MM. Overall, 52% of the participants reported other diagnoses before MM diagnosis, with musculoskeletal disorders (47.8%), such as osteoporosis, costochondritis, or muscle strains, being the most common. The most prevalent initial reported symptom was back pain/vertebral fractures (47%), followed by chest/shoulder pain, including rib pain and fractures (20%), and fatigue/tiredness (19.7%). 40% of participants were diagnosed by direct referral from primary care to haematology without seeing other healthcare professionals whilst 60% consulted additional specialists before diagnosis. The median time from symptom onset to MM diagnosis was 4 months (IQR 2-10 months, range 0-172). Seeing an Allied Healthcare Professional such as a physiotherapist, chiropractor or an osteopath (OR = 0.25, 95% CI [0.12, 0.47], p <0.001), experiencing infection symptoms (OR = 0.32, 95% CI [0.13, 0.76], p = 0.013), and having chest or shoulder pain (OR = 0.45, 95% CI [0.23, 0.86], p = 0.020) were associated with a lower likelihood of being diagnosed with MM within 12 weeks. Older age (OR = 1.04, 95% CI [1.02, 1.07], p = 0.001) was associated with a higher likelihood of diagnosis within 12 weeks. Developing resources for allied health professionals may improve early recognition of MM.


Establishing research priorities for the Infusion Nurses Society.
As the leader in the infusion nursing community, the Infusion Nurses Society (INS) recognizes the critical need for research to support the specialty practice. The purpose of this project was to gain input from INS members to establish research priorities for the organization. In partnership with Wayne State University College of Nursing, INS surveyed its members by using the Delphi approach. The qualitative responses received supported a theoretical framework on which to base an agenda. Respondents identified more problem areas in their practice than in research topics needing further exploration. Four themes, all falling under the overarching domain of patient safety, were identified. By identifying research priorities, INS will be able to guide the direction for research, focus the use of limited financial resources toward the most needed research, and use research to develop and support best practices for the infusion nursing specialty.


Effects on the peripheral nervous system of tunnel workers exposed to acrylamide and N-methylolacrylamide.
This study evaluates the possible toxic effects on the peripheral nervous system of tunnel workers exposed to acrylamide and N-methylolacrylamide during grouting work. Symptoms and nerve conduction velocities (NCV) were recorded for 24 tunnel workers 4 and 16 months after the cessation of exposure during grouting operations. Fifty tunnel workers not involved in grouting operations served as referents. Exposure was assessed by questionnaires, qualitative exposure indices, and measurements of hemoglobin adducts after the cessation of exposure. The exposed workers reported a higher prevalence of symptoms during grouting work than they did in an examination 16 months later. A statistically significant reduction in the mean sensory NCV of the ulnar nerve was observed 4 months postexposure when compared with the values of the reference group (52.3 versus 58.9 m/s, P = 0.001), and the mean ulnar distal delay was prolonged (3.1 versus 2.5 ms, P = 0.001). Both measures were significantly improved when measured 1 year later. Exposure-related improvements were observed from 4 to 16 months postexposure for both the median (motor and sensory NCV and F-response) and ulnar (sensory NCV, F-response) nerves. A significant reversible reduction in the mean sensory amplitude of the median nerve was also observed, while the mean sensory amplitude of the sural nerve was significantly reduced after 16 months. The results indicate demyelinating and axonal changes in peripheral nerves of tunnel workers in relation to exposure to N-methylolacrylamide and acrylamide during grouting operations. The changes were slight, mostly subclinical, and most of the effects were reversible, with normalization after 1 year.


Abdominal computed radiography for the diagnosis of enterolithiasis in horses: 142 cases (2003?2007).
To evaluate the sensitivity and specificity of abdominal computed radiography (CR) for the diagnosis of enterolithiasis in horses and to examine how these parameters are affected by the number and anatomic location of enteroliths and by gas distension of the gastrointestinal tract. Retrospective case series. Horses ? 1 year old that underwent abdominal CR and subsequent exploratory laparotomy or postmortem examination. 3 reviewers blinded to signalment, history, clinical signs, and diagnoses separately evaluated abdominal computed radiographs of horses included in the study. Each set of radiographs was evaluated for the presence or absence of enteroliths, the amount of gas distention, and the image quality. Signalment, definitive diagnosis on the basis of findings on exploratory laparotomy or postmortem examination, and the number and location of enteroliths were obtained from medical records. Of the 142 cases reviewed, 58.4% (83/142) had confirmed enterolithiasis. For the 3 reviewers, overall sensitivity was 85% and specificity was 93%. Sensitivity was lower for small colon enteroliths than for large colon enteroliths (50% and 94.5%, respectively) and was significantly affected by gas distention. Sensitivity was not significantly affected by the number of enteroliths. Computed radiography provided high sensitivity and high specificity for the diagnosis of enterolithiasis in horses. Caution should be exercised when the radiographic results are negative, as the sensitivity for small colon enterolithiasis was relatively low and gas distension negatively affected detection of enteroliths. Abdominal CR is indicated as a diagnostic test in horses examined for colic in geographic regions in which enterolithiasis is endemic.


Diabetes care in remote Australia: the antenatal, postpartum and inter-pregnancy period.
Aboriginal and Torres Strait Islander women experience high rates of diabetes in pregnancy (DIP), contributing to health risks for mother and infant, and the intergenerational cycle of diabetes. By enhancing diabetes management during pregnancy, postpartum and the interval between pregnancies, the DIP Partnership aims to improve health outcomes and reduce risks early in the life-course. We describe a mixed methods formative study of health professional's perspectives of antenatal and post-partum diabetes screening and management, including enablers and barriers to care. Health professionals involved in providing diabetes care in pregnancy, from a range of health services across the Northern Territory, completed the survey (n = 82) and/or took part in interviews and/or focus groups (n = 62). Qualitative findings highlighted factors influencing the delivery of care as reported by health professionals, including: whose responsibility it is, access to care, the baby is the focus and pre-conception care. The main challenges were related to: disjointed systems and confusion around whose role it is to provide follow-up care beyond six weeks post-partum. Quantitative findings indicated that the majority of health professionals reported confidence in their own skills to manage women in the antenatal period (62%, 40/79) and slightly lower rates of confidence in the postpartum interval (57%, 33/58). These findings regarding whose role it is to provide postpartum care, along with opportunities to improve communication pathways and follow up care have informed the design of a complex health intervention to improve health systems and the provision of DIP related care.


Repositioning interprofessional education from the margins to the centre of Australian health professional education - what is required?
Objective This paper examines the implementation and implications of four development and research initiatives, collectively titled the Curriculum Renewal Studies program (CRS), occurring over a 6-year period ending in 2015 and focusing on interprofessional education (IPE) within Australian pre-registration health professional education. Methods The CRS was developed as an action-focused and participatory program of studies. This research and development program used a mixed-methods approach. Structured survey, interviews and extensive documentary analyses were supplemented by semi-structured interviews, focus groups, large group consultations and consensus building methods. Narrative accounts of participants' experiences and an approach to the future development of Australian IPE were developed. Results Detailed accounts of existing Australian IPE curricula and educational activity were developed. These accounts were published and used in several settings to support curriculum and national workforce development. Reflective activities engaging with the findings facilitated the development of a national approach to the future development of Australian IPE - a national approach focused on coordinated and collective governance and development. Conclusion This paper outlines the design of an innovative approach to national IPE governance and development. It explores how ideas drawn from sociocultural theories were used to guide the choice of methods and to enrich data analysis. Finally, the paper reflects on the implications of CRS findings for health professional education, workforce development and the future of Australian IPE. What is known about the topic? IPE to enable the achievement of interprofessional and collaborative practice capabilities is widely accepted and promoted. However, many problems exist in embedding and sustaining IPE as a system-wide element of health professional education. How these implementation problems can be successfully addressed is a health service and education development priority. What does this paper add? The paper presents a summary of how Australian IPE was conceptualised, developed and delivered across 26 universities during the period of the four CRS studies. It points to strengths and limitations of existing IPE. An innovative approach to the future development of Australian IPE is presented. The importance of sociocultural factors in the development of practitioner identity and practice development is identified. What are the implications for practitioners? The findings of the CRS program present a challenging view of current Australian IPE activity and what will be required to meet industry and health workforce expectations related to the development of an Australian interprofessional- and collaborative-practice-capable workforce. Although the directions identified pose considerable challenges for the higher education and health sectors, they also provide a consensus-based approach to the future development of Australian IPE. As such they can be used as a blueprint for national development.


Drainage affects tree growth and C and N dynamics in a minerotrophic peatland.
The lowering of the water table resulting from peatland drainage may dramatically alter C and N cycling in peatland ecosystems, which contain one-third of the total terrestrial C. In this study, tree annual ring width and C (delta(13)C) and N (delta(15)N) isotope ratios in soil and plant tissues (tree foliage, growth rings, and understory foliage) in a black spruce-tamarack (Picea mariana-Larix laricina) mixed-wood forest were examined to study the effects of drainage on tree growth and C and N dynamics in a minerotrophic peatland in west-central Alberta, Canada. Drainage increased the delta(15)N of soil NH4+ from a range of +0.6% per hundred to +2.9% per hundred to a range of +4.6% per hundred to +7.0% per hundred most likely through increased nitrification following enhanced mineralization. Plant uptake of 15N-enriched NH4+ in the drained treatment resulted in higher plant delta15N (+0.8% per hundred to +1.8% per hundred in the drained plots and -3.9% per hundred to -5.4% per hundred in the undrained plots), and deposition of litterfall N enriched with 15N increased the delta15N of total soil N in the surface layer in the drained (+2.9% per hundred) as compared with that in the undrained plots (+0.6% per hundred). The effect of drainage on foliar delta(13)C was species-specific, i.e., only tamarack showed a considerably less negative foliar delta(13)C in the drained (-28.1% per hundred) than in the undrained plots (-29.1% per hundred), indicating improved water use efficiency (WUE) by drainage. Tree ring area increments were significantly increased following drainage, and delta(13)C and delta(15)N in tree growth rings of both species showed responses to drainage retrospectively. Tree-ring delta(13)C data suggested that drainage improved WUE of both species, with a greater and more prolonged response in tamarack than in black spruce. Our results indicate that drainage caused the studied minerotrophic peatland to become a more open ecosystem in terms of C and N cycling and loss. The effects of forested peatland drainage or drying on C and N balances deserve further research in order to better understand their roles in future global change.


Social capital: an individual or collective resource for health?
Although it is now widely acknowledged that the social environment plays an important role in people's health and well-being, there is considerable disagreement about whether social capital is a collective attribute of communities or societies, or whether its beneficial properties are associated with individuals and their social relationships. Using data from the European Social Survey (22 countries, N = 42,358), this study suggests that, rather than having a contextual influence on health, the beneficial properties of social capital can be found at the individual level. Individual levels of social trust and civic participation were strongly associated with self-rated health. At the same time, the aggregate social trust and civic participation variables at the national level were not related to people's subjective health after controlling for compositional differences in socio-demographics. Despite the absence of a main contextual effect, the current study found a more complex cross-level interaction for social capital. Trusting and socially active individuals more often report good or very good health in countries with high levels of social capital than individuals with lower levels of trust and civic participation, but are less likely to do so in countries with low levels of social capital. This suggests that social capital does not uniformly benefit individuals living in the same community or society.


Isolation of a Xanthomonas oryzae pv. oryzae flagellar operon region and molecular characterization of flhF.
An 8.1-kb DNA fragment from Xanthomonas oryzae pv. oryzae that contains six open reading frames (ORF) was cloned. The ORF encodes proteins similar to flagellar proteins FlhB, FlhA, FlhF, and FliA, plus two proteins of unknown function, ORF234 and ORF319, from Bacillus subtilis and other organisms. These ORF have a similar genomic organization to those of their homologs in other bacteria. TheflhF gene product, FlhF, has a GTP-binding motif conserved in its homologs. Unlike its homologs, however, X. oryzae pv. oryzae FlhF carries two transmembrane-like domains. Insertional mutations of theflhF gene with the omega cassette or the kanamycin resistance gene significantly retard but do not abolish the motility of the bacteria. Complementation of the mutants with the wild-type flhF gene restored the motility. The X. oryzae pv. oryzae FlhF interacts with itself; the disease resistance gene product XA21; and a protein homologous to the Pill protein of Pseudomonas aeruginosa, XooPilL, in the yeast two-hybrid system. The biological relevance of these interactions remains to be determined.


Isolation of Vibrio tapetis from two native fish species (Genypterus chilensis and Paralichthys adspersus) reared in Chile and description of Vibrio tapetis subsp. quintayensis subsp. nov.
A group of seven Chilean isolates presumptively belonging to Vibrio tapetis was isolated from diseased fine flounders (Paralichthys adspersus) and red conger eel (Genypterus chilensis) experimentally reared in Quintay (Chile). All isolates were confirmed as members of V. tapetis on the basis of matrix-assisted laser desorption ionization time-of-flight MS, 16S rRNA gene sequencing, DNA-DNA hybridization values and G+C content. The ERIC-PCR and REP-PCR patterns were homogeneous among those isolates recovered from the same host (red conger or fine flounders), but distinct from the type strains V. tapetis subsp. tapetis CECT 4600T and V. tapetis subsp. britannicus CECT 8161T. On the basis of atpA, rpoA, rpoD, recA and pyrH gene sequence similarities (99.7-100 %) and clustering in the phylogenetic trees, the red conger isolates (Q20, Q047, Q48 and Q50) were confirmed as representing V. tapetis subsp. tapetis. However, they differed from V. tapetis subsp. tapetis CECT 4600T in their lipase, alpha quimiotripsin and non-acid phosphatase production. On the other hand, the fine flounder isolates (QL-9T, QL-35 and QL-41) showed rpoD, recA and pyrH gene sequence similarities ranging from 91.6 to 97.7 % with the type strains of the two V. tapetis subspecies (CECT 4600T and CECT 8161T) and consistently clustered together as an independent phylogenetic line within V. tapetis. Moreover, they could be differentiated phenotypically from strains CECT 4600T and CECT 8161T by nine and three different biochemical tests, respectively. In conclusion, the presence of V. tapetis in diseased red conger eel and fine flounder was demonstrated, extending the known host range and geographical location for this pathogen. Furthermore, this study demonstrates that the three isolates from fine flounder represent a novel subdivision within V. tapetis, for which the name V. tapetis subsp. quintayensis subsp. nov. is proposed and with QL-9T (=CECT 8851T=LMG 28759T) as the type strain. Although QL-9T was isolated from kidney of diseased fine flounder specimens, the challenge assays showed that it was non-pathogenic for this species.


Possible Hematological Changes Associated with Acute Gastroenteritis among Kindergarten Children in Gaza.
Gastroenteritis is considered one of the leading causes of morbidity and mortality in children especially in developing countries. It is a major childhood problem in Gaza and one of the most common etiologic agents of iron deficiency anemia (IDA). This study was conducted to investigate possible changes in blood parameters that are associated with gastroenteritis infection among kindergarten children in Gaza. A cross-sectional case-control study was performed including kindergarten children suffering from gastroenteritis and matched healthy control group. Types of etiological agents were identified using standard microbiological and serological procedures. Blood samples were collected for estimation of complete blood count and for determination of serum iron, total iron binding capacity (TIBC), and transferrin saturation. Independent sample t-test was used for comparisons and performed using SPSS software version 17(Chicago Illinois USA). The prevalence of enteric pathogens among cases (88.5% [85/96]) was significantly higher than in asymptomatic controls (11.1% [6/54]). The most common enteric pathogens isolated were Entamoeba histolytica (28% [42/91]) and Giardia lamblia (26.7% [40/91]). Blood tests revealed that 21.8% (21/96) of cases and 14.8% (8/54) of controls had IDA, which were not significantly different. Meanwhile, a significant difference was found between the TIBC and hemoglobin in cases compared to controls. This study indicates that gastroenteritis infection could be considered as a common health problem in kindergarten children in Gaza, and it is possibly associated with changes in hemoglobin concentration and TIBC.


Estrogen receptor alpha gene polymorphisms and bone mineral density: haplotype analysis in women from the United Kingdom.
Genetic factors are important in the pathogenesis of osteoporosis and the estrogen receptor has been suggested as a possible candidate gene for regulation of bone mineral density (BMD). We investigated the relationship between PvuII, XbaI, and dinucleotide (TA)n repeat polymorphisms of the estrogen receptor alpha (ER-alpha) gene and BMD in a study of women from northeast Scotland in the United Kingdom. No significant association was observed between BMD values at the lumbar spine (LS) and femoral neck (FN) in relation to PvuII and XbaI polymorphisms individually, but haplotype analysis showed that BMD values (Z score) were significantly lower in those who carried the Px haplotype (n = 36) compared with those who did not (n = 170) at both the LS (mean +/- SEM; -0.775 +/- 0.125 vs. -0.285 +/- 0.082;p = 0.002) and the FN (-0.888 +/- 0.130 vs. -0.335 +/- 0.083; p = 0.0006). In keeping with this, the Px haplotype also was found to be an independent predictor of LS BMD (p = 0.019) and FN BMD (p = 0.005) in a multiple regression analysis model that included other possible predictors of BMD including age, years since menopause (YSM), hormone-replacement therapy (HRT) use, weight, and height. This model explained 15.7% and 23.4% of the total observed variance in LS and FN BMD, respectively, with the Px haplotype accounting for approximately 3% of the variance at both sites. Although the TA repeat polymorphism was in strong linkage disequilibrium (LD) with the PvuII (chi2 = 109.8; p < 0.0001) and XbaI (chi2 = 97.2; p < 0.0001) polymorphisms, there was no overall association between TA repeat number and BMD. We conclude that polymorphisms of the ER-alpha gene are significantly related to BMD in our population and that this association is dependent on the Px haplotype, suggesting that it is the Px haplotype, or a linked polymorphism, that confers risk.


Remote Assessment of Functional Mobility and Strength in Older Cancer Survivors: Protocol for a Validity and Reliability Study.
Older cancer survivors, faced with both age- and treatment-related morbidity, are at increased and premature risk for physical function limitations. Physical performance is an important predictor of disability, quality of life, and premature mortality, and thus is considered an important target of interventions designed to prevent, delay, or attenuate the physical functional decline. Currently, low-cost, valid, and reliable methods to remotely assess physical performance tests that are self-administered by older adults in the home-setting do not exist, thus limiting the reach, scalability, and dissemination of interventions. This paper will describe the rationale and design for a study to evaluate the accuracy, reliability, safety, and acceptability of videoconferencing and self-administered tests of functional mobility and strength by older cancer survivors in their own homes. To enable remote assessment, participants receive a toolkit and instructions for setting up their test course and communicating with the investigator. Two standard gerontologic performance tests are being evaluated: the Timed Up and Go test and the 30-second chair stand test. Phase 1 of the study evaluates proof-of-concept that older cancer survivors (age ≥60 years) can follow the testing protocol and use a tablet PC to communicate with the study investigator. Phase 2 evaluates the criterion validity of videoconference compared to direct observation of the two physical performance tests. Phase 3 evaluates reliability by enrolling 5-10 participants who agree to repeat the remote assessment (without direct observation). Phase 4 enrolls 5-10 new study participants to complete the remote assessment test protocol. Feedback from participants in each phase is used to refine the test protocol and instructions. Enrollment began in December 2019. Ten participants completed the Phase 1 proof-of-concept. The study was paused in mid-March 2020 due to the COVID-19 pandemic. The study is expected to be completed by the end of 2020. This validity and reliability study will provide important information on the acceptability and safety of using videoconferencing to remotely assess two tests of functional mobility and strength, self-administered by older adults in their homes. Videoconferencing has the potential to expand the reach, scalability, and dissemination of interventions to older cancer survivors, and potentially other older adults, especially in rural areas. ClinicalTrials.gov NCT04339959; https://clinicaltrials.gov/ct2/show/NCT04339959. DERR1-10.2196/20834.


Surgical Techniques for Revascularization in Abdominal Wall Transplantation.
Abdominal wall vascularized composite allotransplantation (AW-VCA) can be considered as a technically feasible option for abdominal wall reconstruction in patients whose abdomen cannot be closed using traditional methods. However, successful initial abdominal wall revascularization in the setting of visceral organ transplantation can pose a major challenge as graft ischemia time, operating in a limited surgical field, and variable recipient and donor anatomy must be considered. Several techniques have been reported to accomplish abdominal wall revascularization. A literature review was performed using PubMed for articles related to "abdominal wall transplantation (AWT)." The authors of this study sorted through this search for relevant publications that describe abdominal wall transplant anatomy, technical descriptions, and outcomes of various techniques. A total of four distinct revascularization techniques were found in the literature. Each of these techniques was described by the respective authors and reported varying patient outcomes. Levi et al published a landmark article in 2003 that described technical feasibility of AWT with anastomosis between donor external iliac and inferior epigastric vessels with recipient common iliac vessels in end-to-side fashion. Cipriani et al described a microsurgical technique with anastomosis between donor and recipient inferior epigastric vessels in an end-to-end fashion. Giele et al subsequently proposed banking the abdominal wall allograft in the forearm to reduce graft ischemia time. Recently, Erdmann et al described the utilization of an arteriovenous loop for synchronous revascularization of abdominal wall and visceral transplants for reduction of ischemia time, operative time, while eliminating the need for further operations. Vascularized composite allotransplantation continues to advance with improving immunotherapy and outcomes in solid organ transplantation. Optimizing surgical techniques remains paramount as the field continues to grow. Refinement of the presented methods will continue as additional evidence and outcomes become available in AW-VCA.


Cytomegalovirus infection in steroid-refractory ulcerative colitis: a case-control study.
Cytomegalovirus (CMV) infection is reported to be a cause of steroid-refractory ulcerative colitis (UC), but the strength of this association has not been tested in a case control study. Controlled studies have also not been performed to determine the sensitivity of available immunohistochemical techniques to detect CMV in this setting. The pathology database at Stanford Hospital was searched for UC patients with a diagnosis of "severe colitis" between the years 1992 and 2002 and medical records were reviewed. Forty patients were identified with refractory UC, defined as poor response to highdose systemic steroids for >2 weeks. Another group of 40 patients with severe, but nonrefractory, UC was case-matched for age and year of biopsy. A series of 40 patients who underwent colectomy for reasons other than inflammatory bowel disease with representative sections of "normal" colon were selected as noncolitis controls. CMV inclusions were detected on hematoxylin and eosin (H&E) in 2 of 40 patients with refractory UC, but not in other patients. Immunohistochemistry (IHC) detected CMV in 10 of 40 (25%) patients with refractory UC and 1 of 40 (2.5%) patients with nonrefractory UC (P = 0.007). The CMV-positive cases initially identified on IHC but not on H&E were re-reviewed for viral inclusions on H&E: 3 had rare, but typical, inclusions; 3 had atypical inclusions; and 3 had no inclusions. CMV was not detected by H&E or IHC in 40 noncolitis controls. Of 10 steroid-refractory UC patients with CMV detected, 7 were refractory to cyclosporin or 6-mercaptopurine/azathioprine (70%) and 6 had undergone proctocolectomy (60%) prior to detection of the CMV. Two patients with recognized CMV infection were treated with gancyclovir, improved, and were able to taper off steroids and avoid proctocolectomy. This study provides evidence that unrecognized and therefore untreated CMV infection is significantly associated with steroid-refractory UC. Moreover, IHC is more sensitive than H&E for detection of CMV and should be considered as part of the routine evaluation of steroid-refractory UC patients, before proceeding with other medical or surgical therapy that may be unnecessary once the CMV is treated.


Beta-alanine improves sprint performance in endurance cycling.
Recent research has shown that chronic dietary beta-alanine (betaALA) supplementation increases muscle carnosine content, which is associated with better performance in short (1-2 min) maximal exercise. Success in endurance competitions often depends on a final sprint. However, whether betaALA can be ergogenic in sprint performance at the end of an endurance competition is at present unknown. Therefore, we investigated the effect of 8-wk betaALA administration in moderately to well-trained cyclists on sprint performance at the end of a simulated endurance cycling race. A double-blind study was performed, which consisted of two experimental test sessions interspersed by an 8-wk betaALA (2-4 g.d; n = 9) or matched placebo (PL; n = 8) supplementation period. In the pretesting and the posttesting, subjects performed a 10-min time trial and a 30-s isokinetic sprint (100 rpm) after a 110-min simulated cycling race. Capillary blood samples were collected for determination of blood lactate concentration and pH. Mean power output during the time trial was approximately 300 W and was similar between PL and betaALA during either the pretesting or the posttesting. However, compared with PL, during the final sprint after the time trial, betaALA on average increased peak power output by 11.4% (95% confidence interval = +7.8 to +14.9%, P = 0.0001), whereas mean power output increased by 5.0% (95% confidence interval = +2.0 to +8.1%, P = 0.005). Blood lactate and pH values were similar between groups at any time. Oral betaALA supplementation can significantly enhance sprint performance at the end of an exhaustive endurance exercise bout.


Epidemiology of sarcopenia and insight into possible therapeutic targets.
Musculoskeletal ageing is a major public health concern owing to demographic shifts in the population. Sarcopenia, generally defined as the age-related loss of muscle mass and function, is associated with considerable risk of falls, loss of independence in older adults and hospitalization with poorer health outcomes. This condition is therefore associated with increased morbidity and health care costs. As with bone mass, muscle mass and strength increase during late adolescence and early adulthood, but begin to decline substantially from ∼50 years of age. Sarcopenia is characterized by many features, which include loss of muscle mass, altered muscle composition, infiltration with fat and fibrous tissue and alterations in innervation. A better understanding of these factors might help us to develop strategies that target these effects. To date, however, methodological challenges and controversies regarding how best to define the condition, in addition to uncertainty about what outcome measures to consider, have delayed research into possible therapeutic options. Most pharmacological agents investigated to date are hormonal, although new developments have seen the emergence of agents that target myostatin signalling to increase muscle mass. In this review we consider the current approaching for defining sarcopenia and discuss its epidemiology, pathogenesis, and potential therapeutic opportunities.


Assessing different mechanisms of toxicity in mountaintop removal/valley fill coal mining-affected watershed samples using Caenorhabditis elegans.
Mountaintop removal-valley fill coal mining has been associated with a variety of impacts on ecosystem and human health, in particular reductions in the biodiversity of receiving streams. However, effluents emerging from valley fills contain a complex mixture of chemicals including metals, metalloids, and salts, and it is not clear which of these are the most important drivers of toxicity. We found that streamwater and sediment samples collected from mine-impacted streams of the Upper Mud River in West Virginia inhibited the growth of the nematode Caenorhabditis elegans. Next, we took advantage of genetic and transgenic tools available in this model organism to test the hypotheses that the toxicity could be attributed to metals, selenium, oxidative stress, or osmotic stress. Our results indicate that in general, the toxicity of streamwater to C. elegans was attributable to osmotic stress, while the toxicity of sediments resulted mostly from metals or metalloids.


Comparative analysis of environmental DNA extraction and purification methods from different humic acid-rich soils.
To establish a rapid, improved soil environmental DNA extraction and purification protocol. Three different soil DNA isolation and four purification strategies were compared on different soil samples with variable rates of success. Bead beating extraction gave significantly higher DNA yields than microwave-based and liquid nitrogen grinding DNA extraction methods. The inclusion of soil washing prior to cell lysis decreased the amount of purification steps required. Although these soil types differed, polyvinylpolypyrrolidone (PVPP)-sepharose 2B column elution was sufficient for all three samples, yielding DNA pure enough for successful application in molecular studies. One soil sample retained 80% of the initial DNA after successful purification. Optimization of a purification protocol confirmed that only a combination of previously described methods proved sufficient in yielding pure environmental DNA from humic-rich soils. Total processing time for DNA extraction and subsequent purification from multiple samples was considerably more rapid than the previously described methods. This study developed a new optimized soil DNA extraction and purification protocol that is suitable for different environmental sources that are rich in humic acid content.


IL-33 induces antigen-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4.
Type 2 cytokines (IL-4, IL-5, and IL-13) play a pivotal role in helminthic infection and allergic disorders. CD4(+) T cells which produce type 2 cytokines can be generated via IL-4-dependent and -independent pathways. Although the IL-4-dependent pathway is well documented, factors that drive IL-4-independent Th2 cell differentiation remain obscure. We report here that the new cytokine IL-33, in the presence of Ag, polarizes murine and human naive CD4(+) T cells into a population of T cells which produce mainly IL-5 but not IL-4. This polarization requires IL-1R-related molecule and MyD88 but not IL-4 or STAT6. The IL-33-induced T cell differentiation is also dependent on the phosphorylation of MAPKs and NF-kappaB but not the induction of GATA3 or T-bet. In vivo, ST2(-/-) mice developed attenuated airway inflammation and IL-5 production in a murine model of asthma. Conversely, IL-33 administration induced the IL-5-producing T cells and exacerbated allergen-induced airway inflammation in wild-type as well as IL-4(-/-) mice. Finally, adoptive transfer of IL-33-polarized IL-5(+)IL-4(-)T cells triggered airway inflammation in naive IL-4(-/-) mice. Thus, we demonstrate here that, in the presence of Ag, IL-33 induces IL-5-producing T cells and promotes airway inflammation independent of IL-4.


Amplification of the c-myb oncogene in a case of human acute myelogenous leukemia.
Amplification is one of the mechanisms by which cellular oncogenes may be altered in their function, possibly leading to neoplastic transformation. The oncogenes c-myc, c- abl , and c-Ki-ras are amplified in several different human neoplasias. The oncogene c-myb, which is specifically expressed and regulated in hematopoietic cells, was found to be amplified in cell lines ML-1, ML-2, and ML-3, which were separately cultured from cells of a patient with acute myelogenous leukemia (AML). A five- to tenfold amplification was correlated with high levels of expression of normal size c-myb messenger RNA and with chromosomal abnormalities in the region 6q22 -24, where the c-myb locus is normally located. Amplification and cytogenetic abnormalities were detected in DNA's from primary and secondary cultures of ML cells, suggesting that they may have contributed to leukemogenesis. The similar AML cell lines HL-60 and ML's contain different amplified oncogenes: c-myc and c-myb, respectively. Alternative activation of structurally and possibly functionally similar oncogenes may distinguish--at the pathogenetic level--phenotypically similar tumors.


Ultrafast spectroscopy of the uranium(IV) and thorium(IV) bis(ketimide) complexes (C5Me5)2An[-N=C(Ph)(CH2Ph)]2 (An = Th, U).
Ultrafast pump-probe spectroscopic studies have been performed on (C 5Me 5) 2U[- N=C(Ph)(CH 2Ph)] 2 and (C 5Me 5) 2Th[- N=C(Ph)(CH 2Ph)] 2 including, for the uranium complex, the first direct measurement of dynamics of electronic deactivation within a 5f-electron manifold. Evidence has been found for strong coupling between the electronic ground state and the f-electron manifold which dominates the dynamics of the excited states of the bis(ketimide) uranium complex. These also demonstrate strong singlet-f manifold coupling, which assists in the deactivation of the photoexcited state of the uranium complex, and provide information on intersystem crossing and internal conversion processes in both complexes.


Frequency stabilization of internal-mirror helium-neon lasers.
A simple and inexpensive frequency stabilization system of a helium-neon two-mode laser with an internal mirror plasma tube is described. The stabilization depends on the comparison of the light intensities of the two operating longitudinal modes. The corresponding frequencies of the modes are symmetrized about the emission line of neon at the transition 3s(2)-2p(4). Experimental results are given. The relative uncertainty of the frequency stabilization is less than 1 part in 10(7).


Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role?
One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (131I) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the 131I-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer.


Adding Increased Energy or Activity to Criterion (A) of the DSM-5 Definition of Hypomania and Mania: Effect on the Diagnoses of 907 Patients From the Bipolar Collaborative Network.
According to DSM-IV, criterion (A) for diagnosing a hypomanic/manic episode is mood change (ie, elevated, expansive, or irritable mood). Criterion (A) was redefined in DSM-5, adding increased energy or activity in addition to mood change. We sought to investigate the effect of adding increased energy or activity to criterion (A) for the diagnosis of hypomania/mania and, thus, bipolar disorder. This analysis of prospectively collected data from the Bipolar Collaborative Network (1995-2002) includes 907 DSM-IV-TR-diagnosed bipolar outpatients (14,306 visits). The Young Mania Rating Scale (YMRS) was administered monthly and used to define DSM-IV and DSM-5 criterion (A) fulfillment during a hypomanic/manic visit. Patients were adults (median age = 40; IQR, 33-49), and over half (56%) were women. Median number of contributed visits was 10 (IQR, 4-23). Applying DSM-5 criterion (A) reduced the number of patients experiencing a hypomanic/manic visit by 34%, compared to DSM-IV. Visits fulfilling DSM-5 criterion (A) had higher odds of experiencing elevated levels of all other mania symptoms, compared to fulfilling DSM-IV criterion (A) only. Association between individual symptoms was strongest with mood elevation and energy or activity (OR [95% CL] = 8.65, [7.91, 9.47]). The 34% reduction in the number of patients being diagnosed with a hypomanic/manic visit shows that the impact of applying DSM-5 criterion (A) is substantial. Fewer hypomanic/manic episodes may be diagnosed by the stricter DSM-5 criterion (A), but the episodes diagnosed are likely to be more severe. The DSM-5 criteria may in general prevent overdiagnosis of bipolar disorder but possibly at the cost of underdiagnosing hypomanic/manic episodes.


Current fluctuations and oscillations in smooth muscle cells from hog carotid artery. Role of the sarcoplasmic reticulum.
Electrical activity of enzymatically isolated, smooth muscle cells from hog carotid arteries was recorded under current clamp and voltage clamp. Under the experimental conditions, membrane potential usually was not stable, and spontaneous hyperpolarizing transients of approximately 100-msec duration were recorded. The amplitude of the transients was markedly voltage dependent and ranged from about 20 mV at a membrane potential of 0 mV to undetectable at membrane potentials negative to -60 mV. Under voltage clamp, transient outward currents displayed a similar voltage dependency. These fluctuations reflect a K+ current; they were abolished by 10 mM tetraethylammonium chloride, a K+ channel blocker, and the current fluctuations reversed direction in high extracellular K+ concentration. Modulators of intracellular Ca2+ concentration also affected electrical activity. Lowering intracellular Ca2+ concentration by addition of 10 mM EGTA to the pipette solution or suppressing sarcoplasmic reticulum function by superfusion with caffeine (10 mM), ryanodine (1 microM), or histamine (3-10 microM) blocked the rapid voltage and current spikes. However, caffeine and histamine induced a much slower hump of outward current before blocking the rapid spikes. This slower transient outward current could be elicited only once after external Ca2+ was removed and is consistent with an activation of K+ channels by Ca2+ released from internal stores. In contrast, removal of external Ca2+ alone failed to abolish the rapid spikes. These results suggest that 1) a Ca2+-dependent K+ conductance can markedly affect the electrical behavior of arterial smooth muscle cells and 2) internal Ca2+ stores, probably the sarcoplasmic reticulum, can support rapid and frequent releases of Ca2+. Exposure to a low concentration of histamine (3 microM) caused synchronization of the irregular, rapid fluctuations giving rise to slow, periodic oscillations of Ca2+-activated K+ conductance with a frequency of 0.1-0.3 Hz. These regular oscillations are reminiscent of periodic Ca2+-induced Ca2+ release, were inhibited by 10 mM caffeine, and point to a modulation of sarcoplasmic reticulum Ca2+ release by histamine.


The Impact of the ACA Medicaid Expansions on Dental Visits by Dental Coverage Generosity and Dentist Supply.
Low-income adults in the United States have historically had limited access to dental coverage and poor dental health outcomes. We examined the effects of the Affordable Care Act Medicaid expansions on dental visits among low-income adults focusing on the generosity of dental coverage and heterogeneity in effects by dentist supply. We used data from 2012, 2014, and 2016 Behavioral Risk Factor Surveillance System surveys. The main analytical sample included nearly 117,000 individuals <138% federal poverty level. We employed a quasi-experimental difference-in-differences design to identify the impact of the state Medicaid expansions on having a dental visit in the past 12 months by the generosity of dental coverage and dentist supply. Medicaid expansions were associated with a nearly 6 percentage-point increase in the likelihood of any dental visits in 2016 (over 10% increase from preexpansion rate) for individuals in Medicaid expanding states with extensive dental benefits. This increase, however, was concentrated in states with high dentist supply with no evidence of improvement in utilization in states with limited dental coverage or low dentist supply. Expanding Medicaid with generous dental coverage improved dental care use only in areas with high dentist supply with no evidence of benefits with low dentist supply or less generous coverage. Improving access to dental care may require both generous coverage and supply-side interventions to increase dentist availability.


The Mouse Genome Database: enhancements and updates.
The Mouse Genome Database (MGD) is a major component of the Mouse Genome Informatics (MGI, http://www.informatics.jax.org/) database resource and serves as the primary community model organism database for the laboratory mouse. MGD is the authoritative source for mouse gene, allele and strain nomenclature and for phenotype and functional annotations of mouse genes. MGD contains comprehensive data and information related to mouse genes and their functions, standardized descriptions of mouse phenotypes, extensive integration of DNA and protein sequence data, normalized representation of genome and genome variant information including comparative data on mammalian genes. Data for MGD are obtained from diverse sources including manual curation of the biomedical literature and direct contributions from individual investigator's laboratories and major informatics resource centers, such as Ensembl, UniProt and NCBI. MGD collaborates with the bioinformatics community on the development and use of biomedical ontologies such as the Gene Ontology and the Mammalian Phenotype Ontology. Recent improvements in MGD described here includes integration of mouse gene trap allele and sequence data, integration of gene targeting information from the International Knockout Mouse Consortium, deployment of an MGI Biomart, and enhancements to our batch query capability for customized data access and retrieval.


Equifinality and its violations in a redundant system: control with referent configurations in a multi-joint positional task.
We tested a prediction that equifinality at the task level may be accompanied by violations of equifinality within the redundant set of elemental variables. Seated subjects grasped a handle, and occupied an initial arm configuration against a bias force produced by a robot. The robot applied a smooth, transient change in the force (perturbation). The subjects were instructed "not to intervene voluntarily" with hand deviations. After the robot force returned to the bias value, the hand returned close to the original position and orientation. Analysis of across-trials variance in the joint configuration space confirmed that most variance of the difference between the initial and final states was compatible with unchanged values of both hand position and orientation. These results provide direct support for the theoretical scheme that combines the ideas of synergies and control with referent configurations.


Analysis of changes in SUMO-2/3 modification during breast cancer progression and metastasis.
SUMOylation is an essential posttranslational modification and regulates many cellular processes. Dysregulation of SUMOylation plays a critical role in metastasis, yet how its perturbation affects this lethal process of cancer is not well understood. We found that SUMO-2/3 modification is greatly up-regulated in metastatic breast cancer cells compared with nonmetastatic control cells. To identify proteins differentially modified by SUMO-2/3 between metastatic and nonmetastatic cells, we established a method in which endogenous SUMO-2/3 conjugates are labeled by stable isotope labeling by amino acids in cell culture (SILAC), immunopurified by SUMO-2/3 monoclonal antibodies and epitope-peptide elution, and analyzed by quantitative mass spectrometry. We identified 66 putative SUMO-2/3-conjugated proteins, of which 15 proteins show a significant increase/decrease in SUMO-2/3 modification in metastatic cells. Targets with altered SUMOylation are involved in cell cycle, migration, inflammation, glycolysis, gene expression, and SUMO/ubiquitin pathways, suggesting that perturbations of SUMO-2/3 modification might contribute to metastasis by affecting these processes. Consistent with this, up-regulation of PML SUMO-2/3 modification corresponds to an increased number of PML nuclear bodies (PML-NBs) in metastatic cells, whereas up-regulation of global SUMO-2/3 modification promotes 3D cell migration. Our findings provide a foundation for further investigating the effects of SUMOylation on breast cancer progression and metastasis.


Master's level in primary health care education - students' and preceptors' perceptions and experiences of the alteration in the clinical areas.
Many Western European countries are undergoing reforms with changes in higher education according to the Bologna declaration for Higher European Education Area. In accordance with these changes, the Master's degree was introduced in specialist nurse education in Sweden in 2007, and as a result changed the curriculum and modified theoretical and clinical areas. The aim of this study was to investigate students' and preceptors' perceptions and experiences of Master's level education in primary health care with a focus on the clinical area. A descriptive design and qualitative approach was used. Interviews with ten students and ten preceptors were performed twice, before and after the clinical practice period. Interviews were audio-recorded, transcribed verbatim and themes formulated. Students perceived alteration in the content of the education at the Master's level such as more independence and additional assignments. The preceptors perceived benefits with the Master's level but were unsure of how to transform theoretical and abstract knowledge into practice. Writing the Master's thesis was seen by students to take time away from clinical practice. For some students and preceptors the content of the Master's level clinical practice area was experienced as vague and indistinct. The students had not expected supervision to be different from earlier experiences, while preceptors felt higher demands and requested more knowledge. Both students and preceptors perceived that education at the Master's level might lead to a higher status for the nurses' profession in primary health care. Students and preceptors experienced both advantages and disadvantages concerning the change in specialist nurse education in primary health care at the Master's level. The altered educational content was experienced as a step forward, but they also questioned how the new knowledge could be used in practice. The relevance of the Master's thesis was questioned. Supervision was seen by students as an introduction to the work of the district nurses' work. Preceptors perceived high demands and did not feel enough qualified for student supervision. Both groups considered it an advantage with the change in education that could result in higher status for nurses working in primary health care.


An ATF/CREB site is the major regulatory element in the human herpesvirus 6 DNA polymerase promoter.
Human herpesvirus 6 (HHV-6) is a recently described T-cell pathogen whose medical relevance and molecular biology are just beginning to be addressed. As a first look at the regulation of viral genes, control of the HHV-6 DNA polymerase promoter was examined. Polymerase gene transcription in HHV-6-infected cells was found to initiate from a single site located 115 bases upstream of the translation start codon. A polymerase promoter-chloramphenicol acetyltransferase reporter gene construct failed to be expressed in uninfected T cells but was highly active in HHV-6-infected cells. Mutational data indicated that the polymerase promoter is TATA-less. Mutational analysis also revealed that the major upstream promoter regulatory element required for transcriptional activity in HHV-6-infected cells is a palindromic ATF/CREB transcription factor binding site. The significance of this site for promoter induction was further demonstrated by the fact that the polymerase ATF/CREB element, when appended to a heterologous basal promoter, is highly responsive to HHV-6 infection. Two protein complexes were found to bind in a specific manner to the ATF/CREB motif in both uninfected and HHV-6-infected T-cell nuclear extracts. Site-specific mutation of the ATF/CREB site resulted in loss of protein binding as well as loss of promoter activity in HHV-6-infected cells.


MSTAR: a submicrometer absolute metrology system.
The Modulation Sideband Technology for Absolute Ranging (MSTAR) sensor permits absolute distance measurement with subnanometer accuracy, an improvement of 4 orders of magnitude over current techniques. The system uses fast phase modulators to resolve the integer cycle ambiguity of standard interferometers. The concept is described and demonstrated over target distances up to 1 m. The design can be extended to kilometer-scale separations.


Nutritional status of children in India: household socio-economic condition as the contextual determinant.
Despite recent achievement in economic progress in India, the fruit of development has failed to secure a better nutritional status among all children of the country. Growing evidence suggest there exists a socio-economic gradient of childhood malnutrition in India. The present paper is an attempt to measure the extent of socio-economic inequality in chronic childhood malnutrition across major states of India and to realize the role of household socio-economic status (SES) as the contextual determinant of nutritional status of children. Using National Family Health Survey-3 data, an attempt is made to estimate socio-economic inequality in childhood stunting at the state level through Concentration Index (CI). Multi-level models; random-coefficient and random-slope are employed to study the impact of SES on long-term nutritional status among children, keeping in view the hierarchical nature of data. Across the states, a disproportionate burden of stunting is observed among the children from poor SES, more so in urban areas. The state having lower prevalence of chronic childhood malnutrition shows much higher burden among the poor. Though a negative correlation (r = -0.603, p < .001) is established between Net State Domestic Product (NSDP) and CI values for stunting; the development indicator is not always linearly correlated with intra-state inequality in malnutrition prevalence. Results from multi-level models however show children from highest SES quintile posses 50 percent better nutritional status than those from the poorest quintile. In spite of the declining trend of chronic childhood malnutrition in India, the concerns remain for its disproportionate burden on the poor. The socio-economic gradient of long-term nutritional status among children needs special focus, more so in the states where chronic malnutrition among children apparently demonstrates a lower prevalence. The paper calls for state specific policies which are designed and implemented on a priority basis, keeping in view the nature of inequality in childhood malnutrition in the country and its differential characteristics across the states.


Involvement of the arginine repressor in lysine biosynthesis of Thermus thermophilus.
Lysine biosynthesis of Thermus thermophilus proceeds in a similar way to arginine biosynthesis, and some lysine biosynthetic enzymes from T. thermophilus so far investigated have the potential to function in arginine biosynthesis. These observations suggest that arginine might regulate the expression of genes for lysine biosynthesis. To test this hypothesis, the argR gene encoding the regulator of arginine biosynthesis was cloned from T. thermophilus and its function in lysine biosynthesis was analysed. The addition of arginine to the culture medium inhibited the growth of an arginase gene knockout mutant of T. thermophilus, which presumably accumulates arginine inside the cells. Arginine-dependent growth inhibition was not alleviated by the addition of ornithine, which is a biosynthetic intermediate of arginine and serves as a peptidoglycan component of the cell wall in T. thermophilus. However, the growth inhibition was cancelled either by the simultaneous addition of lysine and ornithine or by a knockout of the argR gene, suggesting the involvement of argR in regulation of lysine biosynthesis in T. thermophilus. Electrophoretic mobility shift assay and DNase I footprinting revealed that the ArgR protein specifically binds to the promoter region of the major lysine biosynthetic gene cluster. Furthermore, an alpha-galactosidase reporter assay for this promoter indicated that arginine repressed the promoter in an argR-dependent manner. These results indicate that lysine biosynthesis is regulated by arginine in T. thermophilus.


The compulsory psychiatric regime in Hong Kong: Constitutional and ethical perspectives.
This article examines the compulsory psychiatric regime in Hong Kong. Under section 36 of the Mental Health Ordinance, which authorises long-term detention of psychiatric patients, a District Judge is required to countersign the form filled out by the registered medical practitioners in order for the detention to be valid. Case law, however, has shown that the role of the District Judge is merely administrative. This article suggests that, as it currently stands, the compulsory psychiatric regime in Hong Kong is unconstitutional because it fails the proportionality test. In light of this conclusion, the author proposes two solutions to deal with the issue, by common law or by legislative reform. The former would see an exercise of discretion by the courts read into section 36, while the latter would involve piecemeal reform of the relevant provisions to give the courts an explicit discretion to consider substantive issues when reviewing compulsory detention applications. The author argues that these solutions would introduce effective judicial supervision into the compulsory psychiatric regime and safeguard against abuse of process.


Noninvasive tracking of cardiac embryonic stem cells in vivo using magnetic resonance imaging techniques.
Despite rapid advances in the stem cell field, the ability to identify and track transplanted or migrating stem cells in vivo is limited. To overcome this limitation, we used magnetic resonance imaging (MRI) to detect and follow transplanted stem cells over a period of 28 days in mice using an established myocardial infarction model. Pluripotent mouse embryonic stem (mES) cells were expanded and induced to differentiate into beating cardiomyocytes in vitro. The cardiac-differentiated mES cells were then loaded with superparamagnetic fluorescent microspheres (1.63 microm in diameter) and transplanted into ischemic myocardium immediately following ligation and subsequent reperfusion of the left anterior descending coronary artery. To identify the transplanted stem cells in vivo, MRI was performed using a Varian Inova 4.7 Tesla scanner. Our results show that (a) the cardiac-differentiated mES were effectively loaded with superparamagnetic microspheres in vitro, (b) the microsphere-loaded mES cells continued to beat in culture prior to transplantation, (c) the transplanted mES cells were readily detected in the heart in vivo using noninvasive MRI techniques, (d) the transplanted stem cells were detected in ischemic myocardium for the entire 28-day duration of the study as confirmed by MRI and post-mortem histological analyses, and (e) concurrent functional MRI indicated typical loss of cardiac function, although significant amelioration of remodeling was noted after 28 days in hearts that received transplanted stem cells. These results demonstrate that it is feasible to simultaneously track transplanted stem cells and monitor cardiac function in vivo over an extended period using noninvasive MRI techniques.


Three decades of experience with emergency portacaval shunt for acutely bleeding esophageal varices in 400 unselected patients with cirrhosis of the liver.
Emergency treatment of acute bleeding is of singular and paramount importance in the therapy of portal hypertension and esophagogastric varices. Accordingly, for more than three decades we have conducted prospective studies of emergency therapy, and particularly of emergency portacaval shunt (EPCS). Emergency portacaval shunt was performed upon 400 patients with cirrhosis of the liver and acutely bleeding esophagogastric varices according to three principles: operation within eight hours of initial contact; unselected patients, meaning that no patient with variceal bleeding caused by hepatic disease was excluded from EPCS, and prospective study, meaning that a well-defined protocol was consistently used and data were collected on-line. Patients were divided into an early group of 180 treated from 1963 to 1978 and a recent group of 220 treated from 1978 to July, 1990, with similar characteristics, but strikingly different outcome. Follow-up rates at one, five, and ten years were 100, 98, and 97 percent, respectively; 96 percent of patients underwent EPCS five or more years ago. Proof of acute variceal bleeding and of cirrhosis of the liver (alcoholic in 95 percent) was obtained in every patient. Child's risk classes determined quantitatively were A in 11 percent of the patients, B in 65 percent, and C in 24 percent. All patients had a direct portacaval shunt, side-to-side in 85 percent, which reduced the mean portal vein to inferior vena cava pressure gradient from 271 to 21 mm saline solution. All but four patients (99 percent) had immediate and permanent control of variceal bleeding. Thrombosis of the shunt occurred in only two patients (0.5 percent). Survival rates at 30 days, five years, ten years, and 15 years in the early group were 58, 40, 30, and 30 percent, respectively, while in the recent group they were 85, 78, 71, and 57 percent, respectively (p < 0.0001). Other striking gains in the recent group were abstention from alcohol, improvement in liver function and improvement in Child's class, all in 70 percent of patients. Recurrent portal-systemic encephalopathy occurred in 9 percent of the early group and 8 percent of the recent group. Emergency portacaval shunt substantially improved survival and quality of life of patients with cirrhosis of the liver and bleeding varices. Our results are attributable to rapid and simplified diagnosis, prompt operation, an organized system of care, and rigorous, lifelong follow-up evaluation that emphasized abstinence from alcohol and dietary protein control. Transplantation of the liver is infrequently required in patients whose bleeding is permanently controlled.


Decoding non-unique oligonucleotide hybridization experiments of targets related by a phylogenetic tree.
The reliable identification of presence or absence of biological agents ("targets"), such as viruses or bacteria, is crucial for many applications from health care to biodiversity. If genomic sequences of targets are known, hybridization reactions between oligonucleotide probes and targets performed on suitable DNA microarrays will allow to infer presence or absence from the observed pattern of hybridization. Targets, for example all known strains of HIV, are often closely related and finding unique probes becomes impossible. The use of non-unique oligonucleotides with more advanced decoding techniques from statistical group testing allows to detect known targets with great success. Of great relevance, however, is the problem of identifying the presence of previously unknown targets or of targets that evolve rapidly. We present the first approach to decode hybridization experiments using non-unique probes when targets are related by a phylogenetic tree. Using a Bayesian framework and a Markov chain Monte Carlo approach we are able to identify over 94% of known targets and assign up to 70% of unknown targets to their correct clade in hybridization simulations on biological and simulated data. Software implementing the method described in this paper and datasets are available from http://algorithmics.molgen.mpg.de/probetrees.


High-fructose corn syrup enhances intestinal tumor growth in mice.
Excessive consumption of beverages sweetened with high-fructose corn syrup (HFCS) is associated with obesity and with an increased risk of colorectal cancer. Whether HFCS contributes directly to tumorigenesis is unclear. We investigated the effects of daily oral administration of HFCS in adenomatous polyposis coli (APC) mutant mice, which are predisposed to develop intestinal tumors. The HFCS-treated mice showed a substantial increase in tumor size and tumor grade in the absence of obesity and metabolic syndrome. HFCS increased the concentrations of fructose and glucose in the intestinal lumen and serum, respectively, and the tumors transported both sugars. Within the tumors, fructose was converted to fructose-1-phosphate, leading to activation of glycolysis and increased synthesis of fatty acids that support tumor growth. These mouse studies support the hypothesis that the combination of dietary glucose and fructose, even at a moderate dose, can enhance tumorigenesis.


Ceramide and other sphingolipids in cellular responses.
Formerly considered to serve only as structural components, sphingolipids are emerging as an important group of signaling molecules involved in many cellular events, including cell growth, senescence, meiotic maturation, and cell death. They are also implicated in functions such as inflammation and the responses to heat shock and genotoxic stress. Defects in the metabolism of sphingolipids are related to various genetic disorders, and sphingolipids have the potential to serve as therapeutic agents for human diseases such as colon cancer and viral or bacterial infections. The best-studied member of this family, ceramide, which also serves as the structural backbone for other sphingolipids, is an important mediator in multiple cellular signaling pathways. The metabolism and functions of sphingolipids are discussed in this review, with a focus on ceramide regulation in various cellular responses.


Brain Structure Linking Delay Discounting and Academic Performance.
As a component of self-discipline, delay discounting refers to the ability to wait longer for preferred rewards and plays a pivotal role in shaping students' academic performance. However, the neural basis of the association between delay discounting and academic performance remains largely unknown. Here, we examined the neuroanatomical substrates underlying delay discounting and academic performance in 214 adolescents via voxel-based morphometry (VBM) by performing structural magnetic resonance imaging (S-MRI). Behaviorally, we confirmed the significant correlation between delay discounting and academic performance. Neurally, whole-brain regression analyses indicated that regional gray matter volume (rGMV) of the left dorsolateral prefrontal cortex (DLPFC) was associated with both delay discounting and academic performance. Furthermore, delay discounting partly accounted for the association between academic performance and brain structure. Differences in the rGMV of the left DLPFC related to academic performance explained over one-third of the impact of delay discounting on academic performance. Overall, these results provide the first evidence for the common neural basis linking delay discounting and academic performance. Hum Brain Mapp 38:3917-3926, 2017. © 2017 Wiley Periodicals, Inc.