New ND-FISH-Positive Oligo Probes for Identifying Thinopyrum Chromosomes in Wheat Backgrounds.
Thinopyrum has been widely used to improve wheat (Triticum aestivum L.) cultivars. Non-denaturing fluorescence in situ hybridization (ND-FISH) technology using oligonucleotides (oligo) as probes provides a convenient and efficient way to identify alien chromosomes in wheat backgrounds. However, suitable ND-FISH-positive oligo probes for distinguishing Thinopyrum chromosomes from wheat are lacking. Two oligo probes, Oligo-B11 and Oligo-pThp3.93, were designed according to the published Thinopyrum ponticum (Th. ponticum)-specific repetitive sequences. Both Oligo-B11 and Oligo-pThp3.93 can be used for ND-FISH analysis and can replace conventional GISH and FISH to discriminate some chromosomes of Th. elongatum, Th. intermedium, and Th. ponticum in wheat backgrounds. The two oligo probes provide a convenient way for the utilization of Thinopyrum germplasms in future wheat breeding programs.


[Uretero-nephroscopy. Personal experience].
The authors present the personal experience concerning with the use of the rigid ureteropyeloscopes. Two groups of patients have been studied. In the first one (14 subjects) the ureteropyeloscopy was performed either with diagnostic or therapeutic purposes, in the second one, just as upper urinary tract endoscopic control in patients previously submitted to distal ureteral resection and ureteroneocystostomy for urothelial neoplasia of the distal ureter. The authors presenting the personal results and complications, discuss the indications for the upper urinary tract endoscopy with rigid instruments.


Hierarchical micro/submicrometer-scale structured scaffolds prepared via coaxial electrospinning for bone regeneration.
In this study, a cell-free bone tissue engineering scaffold based on core-sheath fibers with micro/submicro-scale structures were fabricated for bone regeneration. The composite fibers were prepared by coaxial electrospinning with cellulose acetate (CA) core solution and a sheath solution consisting of a mixture of silk fibroin (SF) and polyethylene oxide (PEO) loaded with nano-hydroxyapatite (nHAP) and bone morphogenetic protein 2 (BMP-2). The scanning electron microscopy results indicated that a submicro-scaled elliptical pattern formed throughout the entire sheath surface and that these patterned fibers formed a scaffold with microscale interconnected micropores. The fabricated scaffolds with micro/submicro-scale structures displayed good biocompatibility and increased mechanical properties compared to scaffolds based on single-component SF fibers without CA as the core. The results obtained with enzyme-linked immunosorbent assays (ELISAs) indicated that rapid initial release of BMP-2 from the scaffold occurs during the first few days, followed by slow and sustained release for as long as three weeks. The scaffold had a more profound effect on the attachment, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro compared to scaffolds without nHAP and BMP-2. Furthermore, in vivo studies indicated that this scaffold markedly enhanced bone regeneration at 12 weeks post-implantation. Taken together, our findings suggest that the hierarchical micro/submicro-scale structure scaffold consisting of core-sheath fibers acted as a good carrier for sustained BMP-2 release and that it can be used as a replacement material for bone grafts.


PrOnto database : GO term functional dissimilarity inferred from biological data.
Moonlighting proteins are defined by their involvement in multiple, unrelated functions. The computational prediction of such proteins requires a formal method of assessing the similarity of cellular processes, for example, by identifying dissimilar Gene Ontology terms. While many measures of Gene Ontology term similarity exist, most depend on abstract mathematical analyses of the structure of the GO tree and do not necessarily represent the underlying biology. Here, we propose two metrics of GO term functional dissimilarity derived from biological information, one based on the protein annotations and the other on the interactions between proteins. They have been collected in the PrOnto database, a novel tool which can be of particular use for the identification of moonlighting proteins. The database can be queried via an web-based interface which is freely available at http://tagc.univ-mrs.fr/pronto.


Tuning of CHO secretional machinery improve activity of secreted therapeutic sulfatase 150-fold.
Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. The recombinant production of such sulfatases suffers greatly from both low product activity and yield, further limiting accessibility for patient groups. To mitigate the low product activity, we have investigated cellular properties through computational evaluation of cultures with varying media conditions and comparison of two CHO clones with different levels of one active sulfatase variant. Transcriptome analysis identified 18 genes in secretory pathways correlating with increased sulfatase production. Experimental validation by upregulation of a set of three key genes improved the specific enzymatic activity at varying degree up to 150-fold in another sulfatase variant, broadcasting general production benefits. We also identified a correlation between product mRNA levels and sulfatase activity that generated an increase in sulfatase activity when expressed with a weaker promoter. Furthermore, we suggest that our proposed workflow for resolving bottlenecks in cellular machineries, to be useful for improvements of cell factories for other biologics as well.


Development and optimization of hardware for delta relaxation enhanced MRI.
Delta relaxation enhanced magnetic resonance (dreMR) imaging requires an auxiliary B0 electromagnet capable of shifting the main magnetic field within a clinical 1.5 Tesla (T) MR system. In this work, the main causes of interaction between an actively shielded, insertable resistive B0 electromagnet and a 1.5T superconducting system are systematically identified and mitigated. The effects of nonideal fabrication of the field-shifting magnet are taken into consideration through careful measurement during winding and improved accuracy in the design of the associated active shield. The shielding performance of the resultant electromagnet is compared against a previously built system in which the shield design was based on an ideal primary coil model. Hardware and software approaches implemented to eliminate residual image artifacts are presented in detail. The eddy currents produced by the newly constructed dreMR system are shown to have a significantly smaller "long-time-constant" component, consistent with the hypothesis that less energy is deposited into the cryostat of the MR system. With active compensation, the dreMR imaging system is capable of 0.22T field shifts within a clinical 1.5T MRI with no significant residual eddy-current fields.


Methods for expected value of information analysis in complex health economic models: developments on the health economics of interferon-beta and glatiramer acetate for multiple sclerosis.
To develop methods for performing expected value of perfect information (EVPI) analysis in computationally expensive models and to report on the developments on the health economics of interferon-beta and glatiramer acetate in the management of multiple sclerosis (MS) using this methodological framework. Electronic databases and Internet resources, reference lists of relevant articles. A methodological framework was developed for undertaking EVPI analysis for complex models. The framework identifies conditions whereby EVPI may be calculated numerically, where the one-level algorithm sufficiently approximates the two-level algorithm, and whereby metamodelling techniques may accurately approximate the original simulation model. Metamodelling techniques, including linear regression, neural networks and Gaussian processes (GP), were systematically reviewed and critically appraised. Linear regression metamodelling, GP metamodelling and the one-level EVPI approximation were used to estimate partial EVPIs using the ScHARR MS cost-effectiveness model. The review of metamodelling approaches suggested that in general the simpler techniques such as linear regression may be easier to implement, as they require little specialist expertise although may provide only limited predictive accuracy. More complex methods such as Gaussian process metamodelling and neural networks tend to use less-restrictive assumptions concerning the relationship between the model inputs and net benefits, and therefore may permit greater accuracy in estimating EVPIs. Assuming independent treatment efficacy, the 'per patient' EVPI for all uncertainty parameters within the ScHARR MS model is 8855 British pounds. This leads to a population EVPI of 86,208,936 British pounds, which represents the upper estimate for the overall EVPI over 10 years. Assuming all treatment efficacies are perfectly correlated, the overall per patient EVPI is 4271 British pounds. This leads to a population EVPI of 41,581,273 British pounds, which represents the lower estimate for the overall EVPI over 10 years. The partial EVPI analysis, undertaken using both the linear regression metamodel and Gaussian process metamodel clearly, suggests that further research is indicated on the long-term impact of these therapies on disease progression, the proportion of patients dropping off therapy and the relationship between the EDSS, quality of life and costs of care. The applied methodology points towards using more sophisticated metamodelling approaches in order to obtain greater accuracy in EVPI estimation. Programming requirements, software availability and statistical accuracy should be considered when choosing between metamodelling techniques. Simpler, more accessible techniques are open to greater predictive error, whilst sophisticated methodologies may enhance accuracy within non-linear models, but are considerably more difficult to implement and may require specialist expertise. These techniques have been applied in only a limited number of cases hence their suitability for use in EVPI analysis has not yet been demonstrated. A number of areas requiring further research have been highlighted. Further clinical research is required concerning the relationship between the EDSS, costs of care and health outcomes, the rates at which patients drop off therapy and in particular the impact of disease-modifying therapies on the progression of MS. Further methodological research is indicated concerning the inclusion of epidemiological population parameters within the sensitivity analysis; the development of criteria for selecting a metamodelling approach; the application of metamodelling techniques within health economic models and in the specific application to EVI analyses; and the use of metamodelling for EVSI and ENBS analysis.


Reducing Dietary Sodium and Improving Human Health 2.0.
This Special Issue of Nutrients, "Reducing Dietary Sodium and Improving Human Health 2 [...].


Chemical flexibility of heterobimetallic Mn/Fe cofactors: R2lox and R2c proteins.
A heterobimetallic Mn/Fe cofactor is present in the R2 subunit of class Ic ribonucleotide reductases (R2c) and in R2-like ligand-binding oxidases (R2lox). Although the protein-derived metal ligands are the same in both groups of proteins, the connectivity of the two metal ions and the chemistry each cofactor performs are different: in R2c, a one-electron oxidant, the Mn/Fe dimer is linked by two oxygen bridges (μ-oxo/μ-hydroxo), whereas in R2lox, a two-electron oxidant, it is linked by a single oxygen bridge (μ-hydroxo) and a fatty acid ligand. Here, we identified a second coordination sphere residue that directs the divergent reactivity of the protein scaffold. We found that the residue that directly precedes the N-terminal carboxylate metal ligand is conserved as a glycine within the R2lox group but not in R2c. Substitution of the glycine with leucine converted the resting-state R2lox cofactor to an R2c-like cofactor, a μ-oxo/μ-hydroxo-bridged MnIII/FeIII dimer. This species has recently been observed as an intermediate of the oxygen activation reaction in WT R2lox, indicating that it is physiologically relevant. Cofactor maturation in R2c and R2lox therefore follows the same pathway, with structural and functional divergence of the two cofactor forms following oxygen activation. We also show that the leucine-substituted variant no longer functions as a two-electron oxidant. Our results reveal that the residue preceding the N-terminal metal ligand directs the cofactor's reactivity toward one- or two-electron redox chemistry, presumably by setting the protonation state of the bridging oxygens and thereby perturbing the redox potential of the Mn ion.


Effect of biomolecules derived from human platelet-rich plasma on the ex vivo expansion of human adipose-derived mesenchymal stem cells for clinical applications.
Mesenchymal stem cells are a tool in cell therapies but demand a large cell number per treatment, for that, suitable culture media is required which contains fetal bovine serum (FBS). However, for cell-based therapy applications, the use of FBS is problematic. Several alternatives to FBS have been explored, including human derivatives from platelet-rich plasma (hD-PRP). Although various studies have evaluated the impact of hD-PRP on MSC proliferation and differentiation, few of them have assessed their influence on processes, such as metabolism and gene expression. Here, we cultured human adipose-derived MSCs (hAD-MSCs) in media supplemented with either 10% hD-PRP (hD-PRP-SM) or 10% FBS (FBS-SM) in order to characterize them and evaluate the effect of hD-PRP on cell metabolism, gene expression of associated regenerative factors, as well as chromosome stability during cell expansion. We found that hAD-MSCs cultured in hD-PRP-SM have a greater cell elongation but express similar surface markers; in addition, hD-PRP-SM promoted a significant osteogenic differentiation in the absence of differentiation medium and increased the growth rate, maintaining chromosomal stability. In terms of cell metabolic profile, hAD-MSC behavior did not reveal any differences between both culture conditions. Conversely, significant differences in collagen I and angiopoietin 2 expression were observed between both conditions. The present results suggest that hD-PRP may influence hAD-MSC behavior.


Melanotic neuroectodermal tumour of infancy.
Melanotic neuroectodermal tumour of infancy (MNTI) is a rare benign tumour of neural crest origin that was first described by Krompecher in 1918.1 It is predominantly found in infancy, with about 92% of cases below the age of 12 months and 82% below the age of 6 months. The predominant site of origin is in the premaxilla though it is reported at other sites also including the skull, the mandible, the epididymis and the brain.2 The lesions often have areas of bluish discolouration on the surface and are characterised by displacement of the involved tooth bud and local aggressiveness. The present report deals with two cases of MNTI, a 5-month-old baby girl and a 6-month-old baby boy who reported to the Department of Oral and Maxillofacial Pathology, Dr R Ahmed Dental College and Hospital, Kolkata, India. The clinical, radiological, histological and immunohistochemical findings, confirmed the diagnosis of MNTI. Flow cytometry was performed to analyse aneuploidy. The tumours were treated surgically with no history of recurrence to date.


Decreased IDO1-dependent tryptophan metabolism in aged lung during influenza.
Influenza epidemics remain a leading cause of morbidity and mortality worldwide. In the current study, we investigated the impact of chronological ageing on tryptophan metabolism in response to influenza infection.Examination of metabolites present in plasma collected from critically ill patients identified tryptophan metabolism as an important metabolic pathway utilised specifically in response to influenza. Using a murine model of influenza infection to further these findings illustrated that there was decreased production of kynurenine in aged lung in an indoleamine-pyrrole 2,3-dioxygenase-dependent manner that was associated with increased inflammatory and diminished regulatory responses. Specifically, within the first 7 days of influenza, there was a decrease in kynurenine pathway mediated metabolism of tryptophan, which resulted in a subsequent increase in ketone body catabolism in aged alveolar macrophages. Treatment of aged mice with mitoquinol, a mitochondrial targeted antioxidant, improved mitochondrial function and restored tryptophan metabolism.Taken together, our data provide additional evidence as to why older persons are more susceptible to influenza and suggest a possible therapeutic to improve immunometabolic responses in this population.


The Small and Efficient Language Network of Polyglots and Hyper-polyglots.
Acquiring a foreign language is challenging for many adults. Yet certain individuals choose to acquire sometimes dozens of languages and often just for fun. Is there something special about the minds and brains of such polyglots? Using robust individual-level markers of language activity, measured with fMRI, we compared native language processing in polyglots versus matched controls. Polyglots (n = 17, including nine "hyper-polyglots" with proficiency in 10-55 languages) used fewer neural resources to process language: Their activations were smaller in both magnitude and extent. This difference was spatially and functionally selective: The groups were similar in their activation of two other brain networks-the multiple demand network and the default mode network. We hypothesize that the activation reduction in the language network is experientially driven, such that the acquisition and use of multiple languages makes language processing generally more efficient. However, genetic and longitudinal studies will be critical to distinguish this hypothesis from the one whereby polyglots' brains already differ at birth or early in development. This initial characterization of polyglots' language network opens the door to future investigations of the cognitive and neural architecture of individuals who gain mastery of multiple languages, including changes in this architecture with linguistic experiences.


The transcription factor C/EBP-β mediates constitutive and LPS-inducible transcription of murine SerpinB2.
SerpinB2 or plasminogen activator inhibitor type 2 (PAI-2) is highly induced in macrophages in response to inflammatory stimuli and is linked to the modulation of innate immunity, macrophage survival, and inhibition of plasminogen activators. Lipopolysaccharide (LPS), a potent bacterial endotoxin, can induce SerpinB2 expression via the toll-like receptor 4 (TLR4) by ∼1000-fold over a period of 24 hrs in murine macrophages. To map the LPS-regulated SerpinB2 promoter regions, we transfected reporter constructs driven by the ∼5 kb 5'-flanking region of the murine SerpinB2 gene and several deletion mutants into murine macrophages. In addition, we compared the DNA sequence of the murine 5' flanking sequence with the sequence of the human gene for homologous functional regulatory elements and identified several regulatory cis-acting elements in the human SERPINB2 promoter conserved in the mouse. Mutation analyses revealed that a CCAAT enhancer binding (C/EBP) element, a cyclic AMP response element (CRE) and two activator protein 1 (AP-1) response elements in the murine SerpinB2 proximal promoter are essential for optimal LPS-inducibility. Electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrated that LPS induces the formation of C/EBP-β containing complexes with the SerpinB2 promoter. Importantly, both constitutive and LPS-induced SerpinB2 expression was severely abrogated in C/EBP-β-null mouse embryonic fibroblasts (MEFs) and primary C/EBP-β-deficient peritoneal macrophages. Together, these data provide new insight into C/EBP-β-dependent regulation of inflammation-associated SerpinB2 expression.


The HPV E2-Host Protein-Protein Interactions: A Complex Hijacking of the Cellular Network.
Over 100 genotypes of human papillomaviruses (HPVs) have been identified as being responsible for unapparent infections or for lesions ranging from benign skin or genital warts to cancer. The pathogenesis of HPV results from complex relationships between viral and host factors, driven in particular by the interplay between the host proteome and the early viral proteins. The E2 protein regulates the transcription, the replication as well as the mitotic segregation of the viral genome through the recruitment of host cell factors to the HPV regulatory region. It is thereby a pivotal factor for the productive viral life cycle and for viral persistence, a major risk factor for cancer development. In addition, the E2 proteins have been shown to engage numerous interactions through which they play important roles in modulating the host cell. Such E2 activities are probably contributing to create cell conditions appropriate for the successive stages of the viral life cycle, and some of these activities have been demonstrated only for the oncogenic high-risk HPV. The recent mapping of E2-host protein-protein interactions with 12 genotypes representative of HPV diversity has shed some light on the large complexity of the host cell hijacking and on its diversity according to viral genotypes. This article reviews the functions of E2 as they emerge from the E2/host proteome interplay, taking into account the large-scale comparative interactomic study.


Joint sparse representation of brain activity patterns in multi-task fMRI data.
A single-task functional magnetic resonance imaging (fMRI) experiment may only partially highlight alterations to functional brain networks affected by a particular disorder. Multivariate analysis across multiple fMRI tasks may increase the sensitivity of fMRI-based diagnosis. Prior research using multi-task analysis in fMRI, such as those that use joint independent component analysis (jICA), has mainly assumed that brain activity patterns evoked by different tasks are independent. This may not be valid in practice. Here, we use sparsity, which is a natural characteristic of fMRI data in the spatial domain, and propose a joint sparse representation analysis (jSRA) method to identify common information across different functional subtraction (contrast) images in data from a multi-task fMRI experiment. Sparse representation methods do not require independence, or that the brain activity patterns be nonoverlapping. We use functional subtraction images within the joint sparse representation analysis to generate joint activation sources and their corresponding sparse modulation profiles. We evaluate the use of sparse representation analysis to capture individual differences with simulated fMRI data and with experimental fMRI data. The experimental fMRI data was acquired from 16 young (age: 19-26) and 16 older (age: 57-73) adults obtained from multiple speech comprehension tasks within subjects, where an independent measure (namely, age in years) can be used to differentiate between groups. Simulation results show that this method yields greater sensitivity, precision, and higher Jaccard indexes (which measures similarity and diversity of the true and estimated brain activation sources) than does the jICA method. Moreover, superiority of the jSRA method in capturing individual differences was successfully demonstrated using experimental fMRI data.


Developmental coordination disorder and overweight and obesity in children aged 9-14 y.
Developmental coordination disorder (DCD) is a significant problem that affects between 5 and 9% of all children. Since children with DCD are less likely than their non-DCD peers to participate in physical activities, they may be at greater risk for overweight and obesity. In this report, we examine the relationship between DCD and overweight and obesity in a sample of 578 children aged 9-14 y. We also examine whether the relationship between DCD and overweight/obesity is the same for boys and girls, taking into account sex and age-appropriate differences in percentage body fat and body mass index (BMI) criteria. Our results show that for boys, DCD may be a risk factor for overweight/obesity in childhood and early adolescence. For girls, there is no difference in the prevalence of overweight/obesity between children with and without the disorder.


A 2E''-X2A2' transition of NO3 trapped in solid neon.
NO(3) has been stabilized in a neon matrix at 4.3 K in sufficient yield for detection of the absorptions between 7000 and 10,000 cm(-1), which arise from vibronically allowed transitions from the ground state to levels of the A (2)E'' state. The results confirm and somewhat extend previous gas-phase observations for (14)N(16)O(3). Additional spectra are presented for six other isotopologues of NO(3), four of which possess C(2v) symmetry. The splitting patterns for these species support the previous assignments. Alternations in the spacings of the nu(4) progression are consistent with the occurrence of weak to moderate Jahn-Teller interaction in the A 2E state of NO(3).


Health Equity: The Only Path Forward for Primary Care.
The 2021 National Academies of Sciences, Engineering, and Medicine (NASEM) report on Implementing High-Quality Primary Care identifies 5 high-level objectives regarding payment, access, workforce development, information technology, and implementation. Nine junior primary care leaders (3 internal medicine, 3 family medicine, 3 pediatrics) invited from broad geographies, practice settings, and academic backgrounds used appreciative inquiry to identify priorities for the future of primary care. Highlighting the voices of these early career clinicians, we propose a response to the report from the perspective of early career primary care physicians. Health equity must be the foundation of the future of primary care. Because Barbara Starfield's original 4 Cs (first contact, coordination, comprehensiveness, and continuity) may not be inclusive of the needs of under-resourced communities, we promote an extension to include 5 additional Cs: convenience, cultural humility, structural competency, community engagement, and collaboration. We support the NASEM report's priorities and its focus on achieving health equity. We recommend investing in local communities and preparatory programs to stimulate diverse individuals to serve in health care. Finally, we support a blended value-based care model with risk adjustment for the social complexity of our patients.Appeared as Annals "Online First" article.


Local climatic adaptation in a widespread microorganism.
Exploring the ability of organisms to locally adapt is critical for determining the outcome of rapid climate changes, yet few studies have addressed this question in microorganisms. We investigated the role of a heterogeneous climate on adaptation of North American populations of the wild yeast Saccharomyces paradoxus. We found abundant among-strain variation for fitness components across a range of temperatures, but this variation was only partially explained by climatic variation in the distribution area. Most of fitness variation was explained by the divergence of genetically distinct groups, distributed along a north-south cline, suggesting that these groups have adapted to distinct climatic conditions. Within-group fitness components were correlated with climatic conditions, illustrating that even ubiquitous microorganisms locally adapt and harbour standing genetic variation for climate-related traits. Our results suggest that global climatic changes could lead to adaptation to new conditions within groups, or changes in their geographical distributions.


Tolerance of mixed lipid emulsion in neonates: effect of concentration.
To compare the effect of concentration of a mixed lipid emulsion (50:50 medium chain triglyceride/long chain triglyceride) (MCT/LCT) on lipid tolerance in neonates. A prospective randomised controlled trial of 75 neonates requiring prolonged parenteral nutrition was conducted in the neonatal intensive care units of the Royal Maternity Hospital, Belfast, and the Waveney Hospital, Ballymena. Thirty eight infants received 10% and 37 20% lipid emulsion. Infants were randomly assigned to groups at the start of parenteral nutrition and studied if they required seven or more days of this. Lipid tolerance was assessed by twice weekly measurements of plasma triglyceride and cholesterol concentrations and weekly measurement of non-esterified fatty acids and beta hydroxy butyrate. Anthropometry was carried out weekly. The mean cholesterol in the 10% group was significantly higher within the first seven days of the study compared with the 20% group (3.5 vs 2.87 mmol/l), and continued to rise over the study period in contrast to the 20% group. A similar pattern was observed with the triglyceride concentrations. There was no significant difference in non-esterified fatty acids, beta hydroxy butyrate, or growth between the two groups. Sick neonates show better biochemical tolerance to 20% MCT/LCT emulsion than to 10% emulsion.


An evaluation of western bean cutworm pheromone trapping techniques (Lepidoptera: Noctuidae) in a corn and soybean agroecosystem.
Pheromone traps can be used to monitor for adult western bean cutworms, Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), and for the timing of field scouting. Understanding the effect that different trapping techniques have on adult captures could help corn (Zea mays L.) producers make better pest management decisions. Several approaches to trapping adults were evaluated in 2005 and 2006 by using two different pheromone traps (sticky wing and jug traps) in two different environments (corn or corn/soybean [Glycine max (L.) Merr.] at three different heights (0.6, 1.2, and 1.8 m). There was no significant difference in the trap catches by trap type in either 2005 or 2006. There were significantly more adults captured in traps placed between two cornfields than traps placed between corn/soybean fields during both years. Trap height also was significant, with the traps at 1.2 and 1.8 m catching more moths than traps at 0.6 m during both years. These results show that trapping techniques do affect trap catches and that either trap type placed between two cornfields at either 1.2 or 1.8 m above the ground will maximize trap catches.


Reoxidation of Chromium(III) Products Formed under Different Biogeochemical Regimes.
Hexavalent chromium, Cr(VI), is a widespread and toxic groundwater contaminant. Reductive immobilization to Cr(III) is a treatment option, but its success depends on the long-term potential for reduced chromium precipitates to remain immobilized under oxidizing conditions. In this unique long-term study, aquifer sediments subjected to reductive Cr(VI) immobilization under different biogeochemical regimes were tested for their susceptibility to reoxidation. After reductive treatment for 1 year, sediments were exposed to oxygenated conditions for another 2 years in flow-through, laboratory columns. Under oxidizing conditions, immobilized chromium reduced under predominantly denitrifying conditions was mobilized at low concentrations (≪1 μM Cr(VI); ∼ 3% of Cr(III) deposited) that declined over time. A conceptual model of a limited pool of more soluble Cr(III), and a larger pool of relatively insoluble Cr(III), is proposed. In contrast, almost no chromium was mobilized from columns reduced under predominantly fermentative conditions, and where reducing conditions persisted for several months after introduction of oxidizing conditions, presumably due to the presence of a reservoir of reduced species generated during reductive treatment. The results from this 3-year study demonstrate that biogeochemical conditions present during reductive treatment, and the potential for buildup of reducing species, will impact the long-term sustainability of the remediation effort.


Variables Influencing the Effectiveness of Creatine Supplementation as a Therapeutic Intervention for Sarcopenia.
Sarcopenia is an age-related muscle condition characterized by a reduction in muscle quantity, force generating capacity and physical performance. Sarcopenia occurs in 8-13% of adults ≥ 60 years of age and can lead to disability, frailty, and various other diseases. Over the past few decades, several leading research groups have focused their efforts on developing strategies and recommendations for attenuating sarcopenia. One potential nutritional intervention for sarcopenia is creatine supplementation. However, research is inconsistent regarding the effectiveness of creatine on aging muscle. The purpose of this perspective paper is to: (1) propose possible reasons for the inconsistent responsiveness to creatine in aging adults, (2) discuss the potential mechanistic actions of creatine on muscle biology, (3) determine whether the timing of creatine supplementation influences aging muscle, (4) evaluate the evidence investigating the effects of creatine with other compounds (protein, conjugated linoleic acid) in aging adults, and (5) provide insight regarding the safety of creatine for aging adults.


Neurocardiac and cerebral responses evoked by esophageal vago-afferent stimulation in humans: effect of varying intensities.
This study was designed to determine whether esophageal vago-afferent electrostimulation, over a wide range of stimulus intensities, can sustain a cardiac vago-efferent effect by way of central nervous system processing. Studies were performed in ten healthy male subjects (23.9 +/- 6.3 years). Esophageal electrostimulation was carried out using a stimulating electrode placed in the distal esophagus. Stimulation of esophageal vago-afferent fibres was employed using electrical impulses (200 microseconds at 0.2 Hz x 128 s) varying from 2.7 to 20 mA. Respiratory frequencies, beat-to-beat heart rate autospectra and cerebral evoked potentials were recorded at baseline and at each stimulus intensity in random order. With esophageal electrical stimulation, we observed a small non-significant decrease in heart rate. There was a dramatic shift of the instantaneous heart rate power spectra towards enhanced cardiac vagal modulation with intensities as low as 5 mA. This effect was sustained throughout all intensities with no further change in either the low frequency or high frequency power. Conversely, there was a linear dose response relationship between cerebral evoked potential amplitude and stimulus intensity mainly occurring above perception threshold (10 mA). Esophageal stimulation had no significant effect on heart rate or respiratory frequency at any stimulus intensity. These results indicate that electrical stimulation of the distal esophagus across a wide range of current intensities elicits a reproducible shift in the heart rate power spectrum towards enhanced vagal modulation. The data suggest a closed loop afferent/efferent circuitry wherein tonic visceral afferent impulses appear to elicit a phasic or modulatory vago-efferent cardiac response in healthy subjects.


Oscillating LDL accumulation in normal human aortic arch - shear dependent endothelium.
Abnormal mass transfer of blood components to the arterial walls initiates atherosclerosis. Understating the role of mass transfer within the arterial walls requires quantitative analysis. The oscillating lipid accumulation in the aortic wall is examined in the normal human aortic arch with shear dependent endothelium properties. A semi-permeable nature of the arterial wall computational model, applied in the normal human aortic arch under unsteady normal flow and mass conditions, is incorporated with hydraulic conductivity and permeability treated as wall shear stress dependent. The coupling of fluid dynamics and solute dynamics at the endothelium was achieved by the Kedem-Katchalsky equation. A typical aortic arch blood flow waveform at resting conditions and lasting 800 msec is applied. With constant values of water infiltration and endothelial permeability the surface vertex average normalized luminal concentration is 4.25 % higher than that at the entrance. With shear dependent values the surface vertex average normalized luminal concentration is 7.3 % higher than at the entrance. The luminal surface concentration at the arterial wall is flow-dependent with local variations due to geometric features. Concave sides of the aortic arch exhibit, relatively to the convex ones, elevated low density lipoprotein at all time steps. The degree of elevation in luminal surface LDL concentration is mostly affected from the water infiltration velocity at the vessel wall. Shear dependent endothelial values must be taken into account whenever fluid and mass flow within the arterial system is incorporated.


Behavioral and psychological symptoms and psychotropic drugs among people with cognitive impairment in nursing homes in 2007 and 2013.
The use of psychotropic drugs to treat behavioral and psychological symptoms among people with dementia has been widely questioned because of its limited efficacy and risk of harmful side-effects. The objectives of this study was to compare the prevalence of behavioral and psychological symptoms and the use of psychotropic drug treatments among old people with cognitive impairment living in geriatric care units in 2007 and 2013. Two questionnaire surveys were performed in 2007 and 2013, comprising all those living in geriatric care units in the county of Västerbotten in northern Sweden. A comparison was made between 1971 people from 2007 and 1511 people from 2013. Data were collected concerning psychotropic and antidementia drug use, functioning in the activities of daily living (ADL), cognition, and behavioral and psychological symptoms, using the Multi-Dimensional Dementia Assessment Scale (MDDAS). Between 2007 and 2013, the use of antipsychotic drugs declined from 25.4 to 18.9 %, and of anxiolytic, hypnotic, and sedative drugs from 35.5 to 29.4 %. The prevalence of people prescribed antidepressant drugs remained unchanged while antidementia drug prescription increased from 17.9 to 21.5 %. When controlled for demographic changes, 36 out of 39 behavioral and psychological symptoms showed no difference in prevalence between the years. The use of antipsychotic, anxiolytic, hypnotic, and sedative drugs declined considerably between 2007 and 2013 among old people with cognitive impairment living in geriatric care units. Despite this reduction, the prevalences of behavioral and psychological symptoms remained largely unchanged.


PPP2R5D-Related Intellectual Disability and Neurodevelopmental Delay: A Review of the Current Understanding of the Genetics and Biochemical Basis of the Disorder.
Protein Phosphatase 2 Regulatory Subunit B' Delta (PPP2R5D)-related intellectual disability (ID) and neurodevelopmental delay results from germline de novo mutations in the PPP2R5D gene. This gene encodes the protein PPP2R5D (also known as the B56 delta subunit), which is an isoform of the subunit family B56 of the enzyme serine/threonine-protein phosphatase 2A (PP2A). Clinical signs include intellectual disability (ID); autism spectrum disorder (ASD); epilepsy; speech problems; behavioral challenges; and ophthalmologic, skeletal, endocrine, cardiac, and genital malformations. The association of defective PP2A activity in the brain with a wide range of severity of ID, along with its role in ASD, Alzheimer's disease, and Parkinson's-like symptoms, have recently generated the impetus for further research into mutations within this gene. PP2A, together with protein phosphatase 1 (PP1), accounts for more than 90% of all phospho-serine/threonine dephosphorylations in different tissues. The specificity for a wide variety of substrates is determined through nearly 100 different PP2A holoenzymes that are formed by at least 23 types of regulatory B subunits, and two isoforms each of the catalytic subunit C and the structural subunit A. In the mammalian brain, PP2A-mediated protein dephosphorylation plays an important role in learning and memory. The PPP2R5D subunit is highly expressed in the brain and the PPP2A-PPP2R5D holoenzyme plays an important role in maintaining neurons and regulating neuronal signaling. From 2015 to 2017, 25 individuals with PPP2R5D-related developmental disorder were diagnosed. Since then, Whole-Exome Sequencing (WES) has helped to identify more unrelated individuals clinically diagnosed with a neurodevelopmental disorder with pathological variants of PPP2R5D. In this review, we discuss the current understanding of the clinical and genetic aspects of the disorder in the context of the known functions of the PP2A-PPP2R5D holoenzyme in the brain, as well as the pathogenic mutations in PPP2R5D that lead to deficient PP2A-PPP2R5D dephosphorylation and their implications during development and in the etiology of autism, Parkinson's disease, Alzheimer's disease, and so forth. In the future, tools such as transgenic animals carrying pathogenic PPP2R5D mutations, and patient-derived induced pluripotent stem cell lines need to be developed in order to fully understand the effects of these mutations on different neural cell types.


Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer.
The DNA base excision repair pathway is responsible for the repair of cellular alkylation and oxidative DNA damage. A crucial step in the BER pathway involves the cleavage of baseless sites in DNA by an apurinic/apyrimidinic or baseless (AP) endonuclease (Ape1/ref-1), which is a multifunctional enzyme that acts not only as an AP endonuclease but also as a redox-modifying factor for a variety of transcription factors including Fos, Jun, paired box containing genes (PAX), nuclear factor-kappaB, hypoxia-inducible factor alpha (HIF-1alpha), HIF-like factor (HLF), p53, and others. The expression of Ape1/ref-1 in prostate has not been characterized previously. Ape1/ref-1 nuclear immunohistochemistry levels, scored for intensity as 1+, 2+, or 3+, were 91, 3, and 6% in benign hypertrophy (BPH), 0, 42, and 58% in prostatic intraepithelial neoplasia (PIN) and 3, 30, and 67% in prostate cancer, respectively, clearly showing an increase in Ape1/ref-1 nuclear staining in the PIN and cancer compared with BPH. Furthermore, the level of cytoplasmic staining of Ape1/ref-1 in cancer and PIN were elevated (42 and 36%, respectively) compared with BPH (5%). There was no correlation with prostate-specific antigen values or doubling times to Ape1/ref-1 levels. In conclusion, we have demonstrated that Ape1/ref-1 is dramatically elevated in prostate cancer, the level of staining of Ape1/ref-1 increases from low in BPH to intense in PIN and cancer, and there is an increase in the amount of Ape1/ref-1 in the cytoplasm of PIN and cancer compared with BPH. Given these results, we conclude that Ape1/ref-1 may be a diagnostic marker for early prostate cancer and play a role, through its repair, redox, or both functions, in the physiology of the early development of prostate cancer.


The "Iceberg Phenomenon": As Soon as One Technological Problem in NOTES Is Solved, the Next One Appears!
Though already proclaimed about 7 years ago, natural orifice transluminal endoscopic surgery (NOTES) is still in its early stages. A multidisciplinary working team tried to analyze the technical obstacles and identify potential solutions. After a comprehensive review of the literature, a group of 3 surgeons, 1 gastroenterologist, 10 engineers, and 1 representative of biomedical industry defined the most important deficiencies within the system and then compiled as well as evaluated innovative technologies that could be used to help overcome these problems. These technologies were classified with regard to the time needed for their implementation and associated hindrances, where priority is based on the level of impact and significance that it would make. Both visualization and actuation require significant improvement. Advanced illumination, mist elimination, image stabilization, view extension, 3-dimensional stereoscopy, and augmented reality are feasible options and could optimize visual information. Advanced mechatronic platforms with miniaturized, powerful actuators, and intuitive human-machine interfaces could optimize dexterity, as long as enabling technologies are used. The latter include depth maps in real time, precise navigation, fast pattern recognition, partial autonomy, and cognition systems. The majority of functional deficiencies that still exist in NOTES platforms could be overcome by a broad range of already existing or emerging enabling technologies. To combine them in an optimal manner, a permanent dialogue between researchers and clinicians is mandatory.


Steroid treatment improves cochlear function in the MRL.MpJ-Fas(lpr) autoimmune mouse.
Corticosteroid therapy is used to reverse autoimmune sensorineural hearing loss, although little is known of the mechanism by which this occurs. This has been due to the lack of a suitable animal model with spontaneous hearing loss that is steroid responsive. The present study examined the effects of prednisolone treatment on auditory thresholds in the MRL.MpJ-Fas(lpr) autoimmune mouse to determine its suitability as such a model. Autoimmune mice at 3.5-4. 5 months of age were evaluated by pure-tone auditory brainstem response (ABR) to establish threshold elevations due to the disease. The steroid treatment group was then given prednisolone in their drinking water for 2.5 months, while untreated controls were given tap water. Significantly more steroid treated mice survived to the time of post-treatment ABR evaluation. Half of the steroid treated ears demonstrated either improvement or no change in cochlear function compared to only 25% in the untreated controls. Overall, cochlear thresholds in the untreated controls increased by 14.7 dB, whereas no significant threshold increase was seen in the steroid treated group (4.3 dB) over the treatment period. No qualitative anatomical differences were seen in the ears of those mice surviving to the end of the study. These findings establish the autoimmune mouse as a model for studies of steroid responsive mechanisms within the ear. This could apply to autoimmune sensorineural hearing loss, as well as any hearing disorder for which steroid therapy is recommended.


What do geriatric patients experience during an episode of delirium in acute care hospitals? : A qualitative study.
Predispositions and triggers for delirium, such as noxious agents are known and behavior can be monitored; however, there is little to no information available regarding the experience of patients during delirium episodes. Not much is known about a person's world of experiences, which therefore mostly remains as a sort of black box. This study was motivated by the following question: "What do (Austrian) geriatric patients experience during an episode of delirium in an acute care hospital?" The main objective of this article is to present little snippets from the experiences and to allow geriatric patients to speak for themselves. From 2013 to 2016 interviews were carried out within the framework of a qualitative investigation. For data collection narrative interviews according to Fritz Schütze were employed and 10 interviews were conducted in a hospital setting with German-speaking Austrian patients aged between 75 and 90 years (mean age 80.2 years; 7 female and 3 male). The individual interviews lasted between 60 and 120 min. Primary data in the form of individual interpretation and interpretation groups from interview transcripts were marked and coded according to Mayring. All patients who participated in the interviews subjectively recognized delirium as a negative experience. The data analysis led to three main categories with subcategories: changes in sensory perception, extraordinarily strong emotions and memories. It is important to differentiate between two very different types of memories: firstly, personal fate or life changes and secondly, those regarding experiences of war. Scandinavian and Anglo-American literature describe different categories, such as a change in reality, strong emotions and dramatic episodes in the experience of delirium, which can be transferred to Austria. Others consider the biography of each individual patient in context with the sociocultural history of Austria, especially following developments after 1940.


A mathematical method for determining genome divergence and species delineation using AFLP.
The delineation of bacterial species is presently achieved using direct DNA-DNA relatedness studies of whole genomes. It would be helpful to obtain the same genomically based delineation by indirect methods, provided that descriptions of individual genome composition of bacterial genomes are obtained and included in species descriptions. The amplified fragment length polymorphism (AFLP) technique could provide the necessary data if the nucleotides involved in restriction and amplification are fundamental to the description of genomic divergences. Firstly, in order to verify that AFLP analysis permits a realistic exploration of bacterial genome composition, the strong correspondence between predicted and experimental AFLP data was demonstrated using Agrobacterium strain C58 as a model system. Secondly, a method is proposed for determining current genome mispairing and evolutionary genome divergences between pairs of bacteria, based on arbitrary sampling of genomes by using AFLP. The measure of current genome mispairing was validated by comparison with DNA-DNA relatedness data, which itself correlates with base mispairing. The evolutionary genome divergence is the estimated rate of nucleotide substitution that has occurred since the strains diverged from a common ancestor. Current genome mispairing and evolutionary genome divergence were used to compare members of Agrobacterium, used as a model of closely related genomic species. A strong and highly significant correlation was found between calculated genome mispairing and DNA-DNA relatedness values within genomic species. The canonical 70% DNA-DNA hybridization value used to delineate genomic species was found to correspond to a range of current genome mispairing of 13-13.6%. These limits correspond to 0.097 and 0.104 nucleotide substitutions per site, respectively. In addition, experimental data showed that the large Ti and cryptic plasmids of Agrobacterium had little effect on the estimation of genome divergence. Evolutionary genome divergence was used for phylogenetic inferences. Data showed that members of the same genomic species clustered consistently, as supported by bootstrap resampling. On the basis of these results, it is proposed that the genomic delineation of bacterial species could be based, in future, on phylogenetic groups supported by bootstraps and genome descriptions of individual strains, obtained by AFLP analysis, recorded in accessible databases; this approach might eventually replace DNA-DNA hybridization studies.


In a novel form of IFN-gamma receptor 1 deficiency, cell surface receptors fail to bind IFN-gamma.
Complete IFN-gamma receptor ligand-binding chain (IFNgammaR1) deficiency is a life-threatening autosomal recessive immune disorder. Affected children invariably die of mycobacterial infection, unless bone marrow transplantation is undertaken. Pathogenic IFNGR1 mutations identified to date include nonsense and splice mutations and frameshift deletions and insertions. All result in a premature stop codon upstream from the segment encoding the transmembrane domain, precluding cell surface expression of the receptors. We report herein two sporadic and two familial cases of a novel form of complete IFNgammaR1 deficiency in which normal numbers of receptors are detected at the cell surface. Two in-frame deletions and two missense IFNGR1 mutations were identified in the segment encoding the extracellular ligand-binding domain of the receptor. Eight independent IFNgammaR1-specific mAb's, including seven blocking antibodies, gave recognition patterns that differed between patients, suggesting that different epitopes were altered by the mutations. No specific binding of (125)I-IFN-gamma to cells was observed in any patient, however, and the cells failed to respond to IFN-gamma. The mutations therefore cause complete IFNgammaR1 deficiency by disrupting the IFN-gamma-binding site without affecting surface expression. The detection of surface IFNgammaR1 molecules by specific antibodies, including blocking antibodies, does not exclude a diagnosis of complete IFNgammaR1 deficiency.


The folate precursor p-aminobenzoate is reversibly converted to its glucose ester in the plant cytosol.
Plants synthesize p-aminobenzoate (pABA) in chloroplasts and use it for folate synthesis in mitochondria. It has generally been supposed that pABA exists as the free acid in plant cells and that it moves between organelles in this form. Here we show that fruits and leaves of tomato and leaves of a diverse range of other plants have a high capacity to convert exogenously supplied pABA to its beta-D-glucopyranosyl ester (pABA-Glc), whereas yeast and Escherichia coli do not. High performance liquid chromatography analysis indicated that much of the endogenous pABA in fruit and leaf tissues is esterified and that the total pool of pABA (free plus esterified) varies greatly between tissues (from 0.2 to 11 nmol g-1 of fresh weight). UDP-glucose:pABA glucosyltransferase activity was readily detected in fruit and leaf extracts, and the reaction was found to be freely reversible. p-Aminobenzoic acid beta-D-glucopyranosyl ester esterase activity was also detected in extracts. Subcellular fractionation indicated that the glucosyltransferase and esterase activities are predominantly if not solely cytosolic. Taken together, these results show that reversible formation of pABA-Glc in the cytosol is interposed between pABA production in chloroplasts and pABA consumption in mitochondria. As pABA is a hydrophobic weak acid, its uncharged form is membrane-permeant, and its anion is consequently prone to distribute itself spontaneously among subcellular compartments according to their pH. Esterification of pABA may eliminate such errant behavior and provide a readily reclaimable storage form of pABA as well as a substrate for membrane transporters.


A Study of Leisure Walking Intensity Levels on Mental Health and Health Perception of Older Adults.
Research suggests that different levels of intensity of leisure walking can affect the mental health of older adults. Unfortunately, insufficient evidence exists as to the recommended intensity levels of leisure walking for their health benefits. The purpose of this study was to investigate how leisure walking intensity levels are associated with the mental health and health perceptions of older adults. Using a purposive sampling method, the data of 4,737 adults over the age of 65 were drawn from the 2017 California Health and Interview Survey. The results of analysis of these data showed that older adults who engaged in moderate and vigorous leisure walking reported higher health perceptions than those involved in light leisure walking. In addition, older adults who participated in moderate leisure walking reported higher mental health than those who engaged in light leisure walking. This study suggests that moderate and/or vigorous leisure walking can increase the mental health and health perceptions of older adults.


The dilemma of too few hearts.
The number of patients being listed for heart transplantation continues to escalate. Despite a variety of attempts to increase organ donation, the number of available donor hearts remains unchanged. This imbalance of supply and demand creates medical rationing of donor organs. When the success of heart transplantation became apparent, selection criteria was relaxed, further increasing the disparity between the numbers of donor hearts and potential recipients. Decreasing the demand by tightening the selection criteria is the most reasonable solution at this time.


CRISPR-Cas12a assisted specific detection of mpox virus.
Mpox virus, a member of genus Orthopoxvirus, causes rash and flu-like symptoms in humans. In the recent global outbreak, it was reported from several geographical areas that have not historically reported mpox. Point of care, sensitive and specific mpox diagnostic assays are critical in checking the spread of the disease. We have developed a clustered regularly interspaced short palindromic repeats associated Cas12a nuclease-based assay for detecting mpox virus. Mpox specific conserved sequences were identified in polA (E9L) gene which differ by a single nucleotide polymorphism (SNP) from all the viruses present in the genus Orthopoxvirus. This SNP was exploited in our assay to specifically distinguish mpox virus from other related orthopox viruses with a limit of detection of 1 copy/μl in 30 min. The assay exhibits a sensitive and specific detection of mpox virus which can prove to be of practical value for its surveillance in areas infected with multiple orthopox viruses, especially in hotspots of mpox virus infections.


Prevalence and treatment of eating disorders among Hispanics/Latino Americans in the United States.
We reviewed the recent literature on prevalence rates, and application of evidence-based treatments for eating disorders among Hispanics/Latinos residing in the United States. Lifetime prevalence rates of anorexia nervosa are lower among Hispanic/Latinos than non-Hispanic Whites. There are comparable rates of bulimia nervosa and binge eating disorder (BED) among Hispanic/Latinos and non-Hispanic Whites. BED is the most common eating disorder among Hispanic/Latinos. Evidence-based treatments have begun to be implemented with Hispanics/Latinos. The core concepts of cognitive behavioral therapy for bulimia nervosa and BED apply to this population. Culture-specific adaptations include strengthening the collectivistic framework within an individualistic treatment, psychoeducation of immediate and extended family, and adjustment of meal plans that incorporated cultural foods. There are more similarities than differences in the prevalence of eating disorders across Hispanics/Latinos and non-Hispanic Whites. However, the social context such as immigration status and acculturation is important to consider in the development of eating disorders. In addition, the Westernization of Latin America may change the future relationship of immigration status and development of eating disorder within the United States. Overall, cultural adaptations of evidence-based treatments involved the inclusion of family within treatment, acculturation-related issues, and managing family conflicts that arise because of the changes in eating patterns.


Visual data mining of biological networks: one size does not fit all.
High-throughput technologies produce massive amounts of data. However, individual methods yield data specific to the technique used and biological setup. The integration of such diverse data is necessary for the qualitative analysis of information relevant to hypotheses or discoveries. It is often useful to integrate these datasets using pathways and protein interaction networks to get a broader view of the experiment. The resulting network needs to be able to focus on either the large-scale picture or on the more detailed small-scale subsets, depending on the research question and goals. In this tutorial, we illustrate a workflow useful to integrate, analyze, and visualize data from different sources, and highlight important features of tools to support such analyses.


Relationship between personal and environmental factors and prevalence of acquired physical impairment in Brazil - a population-based study.
The aim of this study was to estimate the relationship between personal and environmental factors and the prevalence of acquired physical impairment in adults and older persons in Brazil. We conducted a cross-sectional study using data from the 2013 National Health Survey. The response variable was self-reported acquired physical impairment. The explanatory variables were sex, race/skin color, education level, social class, paid employment, private health insurance, running water, and connection to a sewer network. The strength of association between the explanatory variables and response variable and respective 95% confidence intervals were estimated using Poisson Regression. Physical impairment was reported by 1.25% of the study population (n=55,369). After complete adjustment, being male and non-white, having a lower level of education, living alone, not being in paid employment, not having private health insurance, not having running water, and not living in a house connected to a sewer network were associated with higher prevalence of acquired physical impairment. The findings show that prevalence of physical impairment was higher among vulnerable groups and that personal and environmental factors are important elements that need to be assessed at the population level.


Long term safety of infliximab.
Infliximab is a chimeric anti-tumour necrosis factor-alpha monoclonal antibody that has been studied for the treatment of Crohn's disease and rheumatoid arthritis. In several placebo controlled, randomized clinical trials and open trials, 771 patients have been given infliximab (a further 192 received placebo). Follow-up for safety has included the time of study (12 weeks after the last infusion), plus three additional years. Acute infusion reactions (headache, fever, chills, urticaria, chest pain) were seen in 17% of patients receiving infliximab compared with 7% of those receiving placebo. While infections were reported more frequently overall in the patients given infliximab (26% over 27 weeks of follow-up versus 16% of placebo-treated patients over 20 weeks of follow-up), there was no increased risk of serious infections. There was no difference in the overall mortality rate between the groups. While low titres of autoantibodies developed in less than 10% of patients, drug-induced lupus was seen in less than 1%, with these cases resolving upon discontinuation of the drug. Overall, infliximab showed an acceptable safety profile.


Peroneal and tibial intraneural ganglion cysts in the knee region: a technical note.
Recent research has resulted in an improved understanding of the pathogenesis and treatment of intraneural ganglia, particularly with respect to the most common form, the peroneal nerve at the fibular neck region. To outline the mechanism for the development and propagation of intraneural ganglia located in the knee region, along with their treatment, as well as highlight how shared principles can be exploited for successful treatment of the more commonly occurring peroneal intraneural ganglia. A surgical approach has been developed for peroneal intraneural cysts based on the pathogenesis. The treatment of the less common tibial intraneural cysts is designed along the same principles. A strategy consisting of (1) disarticulation (resection) of the superior tibiofibular joint (ie, the source), (2) disconnection of the articular branch connection (ie, the conduit), and (3) decompression (rather than resection) of the cyst has improved outcomes and eliminated intraneural recurrences in peroneal intraneural cysts. These same principles and techniques can be applied to the rarer tibial intraneural ganglia derived from the same joint. The mechanism of development and propagation for intraneural cysts in the knee region as well as a surgical technique and its rational are described and illustrated. Understanding the joint-related basis of intraneural cysts leads to simple targeted surgery that addresses the joint, its articular branch, and the cyst. The success of the shared surgical strategy for both peroneal and tibial intraneural ganglia confirms the principles of the unifying articular theory.


Effects of double stocking and weighing frequency on pig performance in wean-to-finish production systems.
Two studies were carried out in different wean-to-finish barns to determine the effects of double stocking on pig growth performance. In Study 1, pigs (n = 1,560) were used in a randomized complete block design with a 2 x 2 factorial arrangement of treatments: initial stocking treatment (Single [52 pigs/pen] vs Double [104 pigs/pen] stocked for 10 wk after weaning) and weighing frequency (High [12 times during the study] vs Low [3 times]) on pig performance from weaning (5.9+/-0.01 kg BW; 17 d of age) to harvest (114+/-0.67 kg BW). Floor and feeder space per pig were 0.650 m2 and 4 cm and 0.325 m2 and 2 cm for the single- and double-stocked treatments, respectively. In Study 2, pigs (n = 1,458) were used in a randomized complete block design to evaluate two initial stocking treatments (Single [27 pigs] vs Double [54 pigs] stocked for 10 wk after weaning) on pig performance from weaning (4.8+/-0.01 kg BW; 15 d of age) to harvest (24 wk after weaning). Floor and feeder space per pig were 0.640 m2 and 3.4 cm and 0.320 m2 and 1.7 cm for single- and double-stocked pens, respectively. In both studies, double-stocked pigs were split at the end of wk 10 into two equal-sized groups of similar mean BW and CV of BW, and one group was moved to a different pen in the same building. In Study 1, performance was not affected (P > 0.10) by frequency of weighing. For the first 10 wk after weaning, the Double compared to the Single treatment had lower ADG (7.7 and 7.9%, for Studies 1 and 2, respectively; P < 0.001) and lighter pigs at wk 10 (6.8 and 7.3%, respectively; P < 0.001). During the first 10 wk in Study 1, Double compared to the Single pigs had lower ADFI (7%; P < 0.001) but similar gain:feed (P > 0.10). From wk 11 to harvest, pigs on Double and Single treatments had similar (P > 0.10) ADG in both studies and, in Study 1, ADFI was unaffected by initial stocking treatment, but double-stocked pigs had greater gain:feed (4%, P < 0.01). Double-stocked pigs required an additional 2 d to reach a fixed harvest BW (P < 0.05) in Study 1 and were lighter (4%; P < 0.05) at 24 wk after weaning in Study 2. Carcass measures were similar (P > 0.10) for double- and single-stocked pigs. Double-stocked pigs that were moved at the end of 10 wk had growth performance similar (P > 0.10) to those that remained in the original pen. In summary, double stocking reduced growth rate to 10 wk after weaning but subsequently had no effect on growth rate and improved feed efficiency.


Physiological measures associated with marathon running performance in high-level male and female homogeneous groups.
The study tested the hypothesis that physiological measurements can predict marathon running performance in a top-level homogeneous group of males and females. Ten male, performance: 2:12:04, coefficient of variation (CV)=2.33%, and 8 female marathon runners, performance: 2:34:53, CV=4.54%, performed an increment test on the treadmill (starting speed, 8 km.h-1; increments, 2 km.h-1; increment duration, 3 min to exhaustion). The heart rate (HR), VO2 and the lactate concentrations were measured at the end of each exercise level. During the recovery time, HR and lactate were measured. Furthermore, echocardiographic, anthropometric and haematologic measurements were made. The results of a stepwise multiple regression analysis using marathon time as the dependent variable yielded R2=0.983 for the male group and R2=0.984 for the female group. The model for the male group used the independent variables lactate value at 10 km.h-1, left ventricular telediastolic diameter (LVD) and lactate value at 22 km.h-1. The model for the female group used the independent variables subscapular skinfold, serum ferritin and sum of six skinfolds. Our study demonstrates that in males and females, physiological parameters can explain the variance in marathon time among elite homogeneous groups.


Isoelectric focusing pattern of acid phosphatase and acid esterase in human blood cells, including thymocytes, T lymphocytes, and B lymphocytes.
Lysosomal acid phosphatase and acid esterase from highly purified, viable human thymocytes, T lymphocytes, B lymphocytes, granulocytes, monocytes, platelets, and erythrocytes were subjected to direct measurement of activity and to isoelectric focusing in polyacrylamide thin-layer slabs. The typical patterns for each cell line were found to be distinctly different from the results recently presented in this journal. The study described here opens a new possibility for the biochemical identification of cells and their functional derivatives and neoplastic variants.


[The practical trend in exams in dermatology and venereology].
Three colored photo tests are given to a student at the examination in dermatology and venereology. Practical skills of the students are checked up at bedside. Such an examination is remarkable for its practical trend; it involves elements of diagnostic search and develops clinical thinking.


Pityriasis Lichenoides, Atypical Pityriasis Lichenoides, and Related Conditions: A Study of 66 Cases.
Pityriasis lichenoides (PLs) is an uncommon skin disease of unknown etiology. In recent years, an atypical form of PL has been described, showing overlapping features with mycosis fungoides (MF) and lymphomatoid papulosis. We studied 66 patients with an initial histopathologic diagnosis of PL (M:F=34:32; median age, 25 y; range, 7 to 85 y). According to clinical and phenotypic features, cases were classified into 4 categories: (1) Conventional PL (characteristic clinical features of PL without phenotypic aberrations) (n=20; M:F=8:12; median age, 37 y; range, 9 to 74 y); (2) Atypical form of PL (characteristic clinical features of PL with phenotypic aberrations) (n=25; M:F=16:9; median age, 21 y; range, 7 to 72 y). Four of these patients subsequently developed MF; (3) Lymphomatoid papulosis (waxing and waning lesions and positivity for CD30) (n=10; M:F=4:6; median age, 41 y; range, 16 to 83 y); (4) MF (clinical features typical of MF) (n=11; M:F=6:5; median age, 17 y; range, 8 to 85 y). Molecular analyses of clonality of the infiltrate did not reveal relevant differences among these 4 groups. Our study suggests that patients with an initial histopathologic diagnosis of PL may belong to different groups, showing that clinicopathologic correlation and complete phenotypic analyses are paramount in order to achieve proper classification. Although the relationship between PL and MF is yet a matter of debate, at the present state of knowledge, patients with a clinicopathologic presentation consistent with PL but with aberrant phenotypic features should be monitored in order to detect a possible evolution into MF.


Long-term clinical outcome analysis of poly-methyl-methacrylate cranioplasty for large skull defects.
The goal of secondary cranioplasty is permanent cerebral protection in an esthetically acceptable fashion. Reconstruction of cranial defects can be performed with several different materials. Alloplastic materials, such as preformed methyl-methacrylate (PMMA) cranioplasties, are an alternative frequently used at our institution. This retrospective analysis was designed to review the outcomes of PMMA cranioplasty for skull defect reconstruction. Seventy consecutive patients who had 78 PMMA cranioplasties placed from 2003 through 2010 were identified. Mechanism of injury, location of cranioplasty, type of original repair, postoperative complications, and follow-up time were reviewed. Of the 70 patients, 6 patients had failure and removal of their original PMMA cranioplasty and reinsertion of another, and 2 patients had failure and removal of 2 cranioplasties with replacement of a third, creating a total of 78 PMMA cranioplasties placed. The predominant mechanism of injury was trauma (64%). The most frequent postoperative complication was infection (13%). With the exception of the 2 patients with implant exposure, no patients reported an unacceptable cosmetic result. An overall complication rate of 24% was seen. The results of previous studies have shown that infection and complication rates of cranioplasties accomplished with bone cement are substantially higher, that titanium-based implants may obscure follow-up imaging for tumor patients, and that the outcomes regarding hydroxyapatite-based ceramics, although similar to PMMA, are associated with a much higher cost. PMMA remains a cost-effective and proven method to repair cranial defects that fulfills the goals of cranial reconstruction for skull defects.


Inguinal Herniation of the Urinary Bladder Presenting as Recurrent Urinary Retention.
Herniation of the urinary bladder into the inguinal canal is an uncommon finding, observed in 0.5-4% of inguinal hernias (Curry (2000)). It is usually associated with other conditions that increase intra-abdominal pressure such as bladder neck obstruction due to prostatic hypertrophy. Consequently, in men, it is usually associated with some degree of urinary retention. We present a 42-year-old man in whom herniation of the urinary bladder was the cause of urinary retention, and not vice versa. The patient was on tumor necrosis factor alpha antagonist (TNFA) (Etanercept) for severe Ankylosing spondylitis. Initially, the urinary retention was thought to be a side effect of the medication, but after the drug was discontinued, urinary retention persisted. CT and MRI demonstrated huge herniation of the urinary bladder into the inguinal canal. Immediately after the hernia was repaired, bladder function was restored. TNF treatment was restarted, and no further urinary symptoms were observed in the next two years of follow-up. In this case, the primary illness and its treatment were distracting barriers to early diagnosis and treatment. In younger patients with a large hernia who develop unexpected urinary retention, herniation of the urinary bladder should be highly considered in the differential diagnosis.


Maxillofacial rehabilitation of an acid attack survivor - The journey from scar to smile.
Acid attack is a form of violent assault involving the act of throwing acid or any corrosive substance such as sulfuric acid, nitric acid, and hydrochloric acid with the intention to disfigure, maim, torture, or kill. A combination of surgical intervention along with prosthetic management using maxillofacial prosthesis serves a good treatment modality for rehabilitation in such cases. The advent of technological advancements has made the rehabilitation procedure easier, faster, and comfortable both for the patient and prosthodontist.


Factors affecting the adsorption of buchnericin LB, a bacteriocin produced by Lactobacillus [correction of Lactocobacillus] buchneri.
Buchnericin-LB adsorbs to gram-positive but not to gram-negative bacteria. The tested gram-positive bacteria were species of Lactobacillus, Pediococcus, Leuconostoc, Enterococcus, Lactococcus, Listeria, Bacillus, Staphylococcus; gram-negative bacteria belonged to the genera Salmonella, Escherichia, Yersinia and Pseudomonas. Buchnericin-LB adsorption depended on pH but not on time and temperature. Also some anions of salts and lipoteichoic acid reduced or inhibited its adsorption. Treatment of cells and cell walls of sensitive bacteria with detergents, organic solvents or enzymes did not affect subsequent binding of buchnericin-LB. Treatment with buchnericin-LB caused sensitive cells to lose high amounts of intracellular K+ ions and UV-absorbing materials and became more permeable to o-nitrophenol-beta-D-galactopyranoside. Buchnericin-LB (640-2560 AU/ml) decreased the colony forming units (99%) and absorbance values of Listeria monocytogenes and Bacillus cereus. These results indicate that the mode of action of buchnericin-LB is bactericidal and its lethal effect is very rapid.


Hyperthermic isolated limb perfusion with tumor necrosis factor alpha, interferon gamma, and melphalan for locally advanced nonmelanoma skin tumors of the extremities: a multicenter study.
Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor alpha (TNF-alpha), interferon gamma, and melphalan has proved to be useful in the treatment of recurrent malignant melanoma and of locally advanced soft tissue sarcomas of the extremities. To determine whether this modality is also effective in the treatment of locally advanced nonmelanoma skin tumors of the extremities. Fifteen patients with locally advanced primary, recurrent, or metastatic skin tumors of the extremities (12 with squamous cell carcinoma and 3 with Merkel cell carcinoma) underwent HILP with TNF-alpha, interferon gamma, and melphalan. Six tumors were localized in the upper extremity (40%), and 9 in the lower extremity (60%). Treatment-related complications, limb salvage rate, local recurrence, and regional and distant metastases were scored during a median follow-up of 20 months. After HILP, 9 patients (60%) showed a complete response (with histopathological confirmation). Four patients (27%) showed a partial response (with histopathological confirmation in 1 patient), and 2 patients (13%) showed no change (with histopathological confirmation in 1 patient and with clinical evidence in 1 patient). Two patients (13%) showed treatment-related complications. The limb salvage was achieved in 12 patients (80%), and the local recurrences developed in 4 patients (27%). During follow-up, regional lymph node metastases were observed in 2 patients (13%) and distant metastases in 2 patients (13%). Based on our results, HILP with TNF-alpha, interferon gamma, and melphalan should be considered as a limb-saving treatment modality in patients with locally advanced nonmelanoma skin tumors of the extremities who would otherwise be candidates for ablative surgery.


A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor.
Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these drugs modulates the stability of the androgen receptor (AR) and resensitizes AR-mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for γ-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC could be repurposed to tackle resistance to antiandrogens in prostate cancer patients.


Excitatory cortical inputs to pallidal neurons via the subthalamic nucleus in the monkey.
How the motor-related cortical areas modulate the activity of the output nuclei of the basal ganglia is an important issue for understanding the mechanisms of motor control by the basal ganglia. In the present study, by using awake monkeys, the polysynaptic effects of electrical stimulation in the forelimb regions of the primary motor and primary somatosensory cortices on the activity of globus pallidus (GP) neurons, especially mediated by the subthalamic nucleus (STN), have been characterized. Cortical stimulation induced an early, short-latency excitation followed by an inhibition and a late excitation in neurons of both the external and internal segments of the GP. It also induced an early, short-latency excitation followed by a late excitation and an inhibition in STN neurons. The early excitation in STN neurons preceded that in GP neurons. Blockade of STN neuronal activity by muscimol (GABA(A) receptor agonist) injection resulted in abolishment of both the early and late excitations evoked in GP neurons by cortical stimulation. At the same time, the spontaneous discharge rate of GP neurons decreased, pauses between the groups of spikes of GP neurons became prominent, and the firing pattern became regular. Injection of (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) [N-methyl-D-aspartate (NMDA) receptor antagonist], but not 1,2,3, 4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium [NBQX (non-NMDA receptor antagonist)], into the STN attenuated the early and late excitations in GP neurons, suggesting that cortico-subthalamic transmission is mediated mainly by NMDA receptors. Interference with the pallido-subthalamic transmission by bicuculline (GABA(A) receptor antagonist) injection into the STN made the inhibition distinct without affecting the early excitation. The present results indicate that the cortico-subthalamo-pallidal pathway conveys powerful excitatory effects from the motor-related cortical areas to the GP with shorter conduction time than the effects conveyed through the striatum.


O-arm-guided balloon kyphoplasty: prospective single-center case series of 54 consecutive patients.
Balloon kyphoplasty is widely used to treat vertebral compression fractures. Procedure outcome and safety are directly linked to precise radiological imaging requiring 1 or 2 C arms to allow correct visualization throughout the procedure. This minimally invasive spinal surgery is associated with radiation exposure for both patient and surgeon. In our center, we switched from using a C-arm to an O-arm image guidance system to perform balloon kyphoplasty. Our preliminary experience is reported in Acta Neurochirurgica, and the encouraging results led us to study this subject more extensively. This article presents our complete results. To the best of our knowledge, there is no comparable clinical series describing O-arm use in kyphoplasty procedures published in the literature. To report our complete results of using the O-arm guidance system to perform balloon kyphoplasty. We prospectively evaluated O-arm-guided kyphoplasty procedure in 54 consecutive patients and measured x-ray exposure and fluoroscopy time. The mean surgical time for the procedure was 38 minutes with a mean fluoroscopy procedure time of 3.1 minutes. The mean fluoroscopy time by level was 2.5 minutes. Mean irradiation dose by procedure was 220 mGy and by level was 166 mGy. There was a significant reduction in fluoroscopy time and x-ray exposure from 5.1 minutes with classic C-arm use to 3.1 minutes when with O-arm use without additional time required for positioning the system. With this new intraoperative system, the overall surgical and fluoroscopy times can be further reduced in the near future.


Cost analysis of informal care: estimates from a national cross-sectional survey in Sweden.
Over the past decades, informal care has increased in most OECD-countries. Informal care is costly to caregivers and to society in the form of lost income and direct costs of providing care. Existing evidence suggests that providing informal care affects caregivers' overall health. However, estimates of the social costs of informal care based on national data on individuals are currently scarce. This study contributes to the existing evidence on the costs of informal care by estimating the direct and indirect costs to caregivers using a purposive national household survey from Sweden. Adopting a bottom-up, prevalence approach, the direct and indirect costs are estimated using the survey data and the value of working time and leisure time from existing sources. The results suggest that around 15% of the adult population of Sweden provide informal care and that such care costs around SEK 152 billion per year (around 3% of GDP; USD 16,3 billion; EUR 14,5 billion), or SEK 128000 per caregiver. Around 55% of costs are in the form of income loss to caregivers. The largest cost items are reduced work hours and direct costs of providing informal care. Replacing informal caregivers with professional care providers would be costly at around SEK 193,6 billion per year. Findings indicate that, even in a country with a relatively generous welfare system, significant resources are allocated toward providing informal care. The costing analysis suggests that effective support initiatives to ease the burden of informal caregivers may be cost-effective.


Rethinking Anatomy: How to Overcome Challenges of Medical Education's Evolution.
Due to scientific and technological development, Medical Education has been readjusting its focus and strategies. Medical curriculum has been adopting a vertical integration model, in which basic and clinical sciences coexist during medical instruction. This context favours the introduction of new complementary technology-based pedagogical approaches. Thus, even traditional core sciences of medical curriculum, like Anatomy, are refocusing their teaching/learning paradigm. We performed a bibliographic review aiming to reflect on Medical Education's current pedagogical trend, by analysing the advantages of the introduction and diversification of pedagogical approaches in Anatomy Education. Anatomy Education's status quo is characterized by: less available teaching time, increasing demands from radiology and endoscopy imaging and other invasive and non-invasive medical techniques, increasing number of medical students and other logistical restrains exposed by the current Medical Education scenario. The traditional learning approach, mainly based on cadaveric dissection, is drifting to complementary newer technologies - such as 3D models or 2D/3D digital imaging - to examine the anatomy of the human body. Also, knowledge transfer is taking different channels, as learning management systems, social networks and computer-assisted learning and assessment are assuming relevant roles. The future holds promising approaches for education models. The development of Artificial Intelligence, Virtual Reality and Learning Analytics could provide analytic tools towards a real-time and personalized learning process. A reflection on Anatomy Education, as a comprehensive model, allows us to understand Medical Education's complexity. Therefore, the present Medical Education context favours a blended learning approach, in which multi-modality pedagogical strategies may become the landmark.


The role of canine superficial ventricular muscle fibers in endocardial impulse distribution.
Thin sections of canine right and left ventricular endocardium and myocardium were studied in a tissue bath to compare conduction properties of intraventricular specialized conducting tissue [Purkinje fibers (PF)], the superficial layers of subendocardial ventricular muscle (SVM), and the deeper ventricular muscle (DVM) below this level. The study was carried out because of observations that some areas of the endocardium, which are devoid of either specialized conducting tissue or of PF-VM junctions between specialized conducting tissue and ventricular muscle, conduct relatively rapidly, favoring specific orientations of propagation. Preparations containing PF, SVM, and DVM were studied electrophysiologically and histologically. A technique of stripping limited areas of endocardium was used to expose DVM in order to determine its intrinsic calculated conduction velocity. In 12 preparations, the average calculated conduction velocity in PF was 1.62 m/sec, and the average in DVM was 0.26 m/sec. The SVM conduction velocity was intermediate between the two, averaging 0.98 m/sec when propagation was parallel to SVM fiber orientation. Conduction velocity transverse to SVM fiber orientation was not significantly different from DVM conduction velocity. Histologically, the most superficial layers of VM were oriented uniformly in the direction of rapid subendocardial conduction, in contrast to DVM fibers in which orientation varied. It is concluded that the geometric arrangement of SVM fibers may provide a means for rapid subendocardial conduction and impulse distribution at a conduction velocity intermediate between PF and DVM in areas devoid of specialized conducting tissue.


Peer mentoring experience on becoming a good doctor: student perspectives.
PASS is a peer-led structured academic mentoring program designed to provide academic assistance for new students in their transition from college to university studies and also for students struggling in certain units. This study aims to establish acquired skills by peer leaders associated with peer-led mentoring via the PASS program, and to explore the role played by these acquired skills in their journey to become a successful doctor. Study participants were forty selected second-year undergraduate medical students at Monash University Malaysia with commendable examination results. Validated pre-test and post-test questionnaires were administered to explore changes in the level of communication, leadership, professional, and pedagogical skills before and after participation in peer mentoring program. Qualitative analysis of focused group interviews was performed by an independent investigator to identify how the skills developed as a peer mentor may help with becoming a good doctor. Major themes were identified with the thematic-analysis approach. Thirty-eight students completed the pre-test and post-test questionnaires. Peer leaders reported improvement in oral and written skills for teaching; increased confidence to give constructive feedback; better stress management; efficient time management; improved interpersonal skills; and enhanced problem-solving and critical thinking capabilities. Eight major themes were identified from the interview and peer leaders reported positive experience of working in diverse environments and shouldering of responsibilities. Peer-led mentoring provides a good opportunity for medical students to shoulder responsibilities as a leader and offers an experience of managing a team of their peers and juniors which in turn may enhance their communication, interpersonal, and leadership skills.


Multiple alignment by aligning alignments.
Multiple sequence alignment is a fundamental task in bioinformatics. Current tools typically form an initial alignment by merging subalignments, and then polish this alignment by repeated splitting and merging of subalignments to obtain an improved final alignment. In general this form-and-polish strategy consists of several stages, and a profusion of methods have been tried at every stage. We carefully investigate: (1) how to utilize a new algorithm for aligning alignments that optimally solves the common subproblem of merging subalignments, and (2) what is the best choice of method for each stage to obtain the highest quality alignment. We study six stages in the form-and-polish strategy for multiple alignment: parameter choice, distance estimation, merge-tree construction, sequence-pair weighting, alignment merging, and polishing. For each stage, we consider novel approaches as well as standard ones. Interestingly, the greatest gains in alignment quality come from (i) estimating distances by a new approach using normalized alignment costs, and (ii) polishing by a new approach using 3-cuts. Experiments with a parameter-value oracle suggest large gains in quality may be possible through an input-dependent choice of alignment parameters, and we present a promising approach for building such an oracle. Combining the best approaches to each stage yields a new tool we call Opal that on benchmark alignments matches the quality of the top tools, without employing alignment consistency or hydrophobic gap penalties. Opal, a multiple alignment tool that implements the best methods in our study, is freely available at http://opal.cs.arizona.edu.


Methodology for Evaluating Models of Telemental Health Delivery Against Population and Healthcare System Needs: Application to Telemental Healthcare for Rural Native Veterans.
Background: Rural American Indian and Alaska Native (AI/AN) Veterans face exceptional barriers to receiving quality mental healthcare. We aimed to identify models of in-person and telemental health service delivery with promise for adaptation and wide dissemination to rural AI/AN Veterans. Methods: Our method for matching specific populations with models of care includes (1) selecting frameworks that represent the healthcare organization's goals, (2) identifying relevant service delivery models for the target population(s), (3) assessing models against the selected frameworks, and (4) summarizing findings across models. We applied this approach to rural AI/AN Veteran populations. Results: Searches identified 13 current models of service delivery for rural AI/AN Veteran, rural AI/AN, and general rural Veteran populations. These models were assessed against four frameworks-the U.S. Department of Veterans Affairs' Office of Rural Health's Promising Practices, Veterans Health Administration's Guide to Mental Health Services, the Institute for Healthcare Improvement's Triple Aim Framework, and the American Indian Telemental Health Clinic framework. Discussion: The one model used for service delivery for rural AI/AN Veterans increases access and is patient-centered but lacks operational feasibility. Models for rural AI/ANs also increase access and are patient-centered but generally lack effectiveness evaluations. Models for rural Veterans demonstrate beneficial effects on mental health outcomes but do not emphasize cultural adaptations to diverse populations. Conclusions: Our approach to selecting models of service delivery considers the needs of operational partners as well as target populations and emphasizes large-scale implementation alongside effectiveness. Pending further testing, this approach holds promise for wider application.


The 6-min Walk Test Reflects Functional Capacity in Primary Care and Obese Patients.
The main purpose of this study was to determine the association between the 6-min walk test distance (6MWTD) and physical functional capacity (PF) in primary care patients, as well as in obese individuals. We studied 351 subjects (age=56.8±14.6 years; BMI=29.4±5.7 kg/m(2); 68% women), including 141 obese subjects (BMI≥30 kg/m(2)), recruited in 10 different family practices. Physical (PCS) and mental component summary of the health-related quality of life (HRQOL) and the 8 sub-scores were measured using the Short Form-36 Health Survey. Anthropometry, vital signs and physical testing were measured according to standardized protocols. Recreational physical activity (LPA) and sedentary levels were determined using the Canadian Community Health Survey. In a stepwise multivariate analysis, 65% of the 6MWTD variance was explained by PF of the HRQOL, age, quadriceps strength, number of chronic diseases, LPA categories, BMI, resting heart rate, PCS, height and TV-viewing categories in primary care subjects. In the obese individuals, PF, age, quadriceps strength and BMI explained 57% of the 6MWTD variance. In these 2 groups, 44% of the 6MWTD variance is explained by PF only. To conclude, the 6MWTD is strongly associated with PF of the HRQOL. Thus, it adequately reflects physical limitations in daily life activities of primary care patients, including obese individuals.


Preference and effect of gustatory sense on sugar-feeding of fire ants.
The red imported fire ant is one of the notorious species of ants all over the world. Sugar is one of the most important components of food and necessary for the survival of ants. Because more than 70% food of fire ants is honeydew produced by Homopteran insects such as aphids and scales. It is well known that beetles, flies, and honey bees can recognize the sugar taste through their legs and antennae, but in the case of fire ants, no records regarding gustatory sense were published. In the current study, considering the importance of sugar bait, we investigated the gustatory sense of the fire ant workers to sucrose via behavioral sequence and gustatory behavior. First, the feeding sequence (ethogram) of the fire ant workers on most preferred sugar (sucrose) solution was observed and categorized. Secondly, the gustatory behavior of treated fire ant workers (without flagellum and foreleg tarsi treated with HCL solution) was observed on the sucrose solution. In addition, using scanning electron microscopy (SEM) techniques, we identified the possible porous sensilla types on antenna flagellum and foreleg tarsi of fire ant workers. Based on the results of feeding sequence, foreleg tarsi of workers were the main body appendages in the detection of the sucrose droplet as compared to antennae flagellum and palps. Feeding time of treated workers with HCL solution was significantly decreased on sucrose solution as compared to those workers having no flagellum. While both types of treated workers have less feeding time in comparison to normal workers. Based on the results of feeding sequence analysis and feeding time, it is indicating that the foreleg tarsi of workers play a more important role in the detection of sucrose solution as compared to antennae flagellum. Based on the SEM results, sensilla chaetic, trichoid II, and basiconic I and II have a clear pore at their tip. This study provides a substantial basis for elucidating the gustatory function of antennal and tarsal sensilla on appendages of fire ant workers to sugars and further baits improvement for the management of fire ants.