Visual acuity in unilateral cataract.
Patching the fellow eye in infancy is a well recognised therapy to encourage visual development in the lensectomised eye in cases of unilateral congenital cataract. The possibility of iatrogenic deficits of the fellow eye was investigated by comparing the vision of these patients with untreated unilateral patients and binocularly normal controls. Sweep visual evoked potentials (VEPs) offer a rapid and objective method for estimating grating acuity. Sweep VEPs were used to estimate acuity in 12 children aged between 4 and 16 years who had had a congenital cataract removed in the first 13 weeks of life. The acuities of aphakic and fellow phakic eye were compared with the monocular acuities of similarly aged children who have good binocular vision, and with children with severe untreated uniocular visual impairment. Recognition linear acuities were measured with a linear Bailey-Lovie logMAR chart and compared with the sweep VEP estimates. A significant difference was found between Bailey-Lovie acuity of the fellow eye of the patient group and the right eye of binocular controls, and the good eye of uniocular impaired patients (one way ANOVA, p < 0.01). However, this was not evident for a similar comparison with sweep VEP estimates. There was no significant difference between the right and left eye acuities in binocular controls measured by the two techniques (paired t test). A loss of recognition acuity in the fellow phakic eye of patients treated for unilateral congenital cataract has been demonstrated with a logMAR chart. This loss was not apparent in children who have severe untreated uniocular visual impairment and may therefore be an iatrogenic effect of occlusion. An acuity loss was not apparent in the patient group using the sweep VEP method. Sweep VEP techniques have a place for objectively studying acuity in infants and in those whose communication difficulties preclude other forms of behavioural test. The mean sweep VEP acuity for the control groups is 20 cpd--that is, about 6/9. When acuities higher than this are under investigation--for example, in older children, slower transient VEP recording may be more appropriate, because higher spatial frequency patterns are not as visible at higher temporal rates (for example, 8 Hz used in sweep VEP recordings).


Transmission of the microsporidian gill parasite, Loma salmonae.
Since it was first reported in 1987 at a hatchery in British Columbia, Loma salmonae has become increasingly important as an emerging parasite affecting the Canadian salmonid aquaculture industry. L. salmonae causes Microsporidial Gill Disease of Salmon (MGDS) in farmed Pacific salmonids, Oncorhynchus spp., resulting in respiratory distress, secondary infections and high mortality rates. In the last decade, laboratory studies have identified key transmission factors for this disease and described the pathogenesis of MGDS. L. salmonae enters the host via the gut, where it injects sporoplasm into a host cell, which then migrates to the heart for a two-week merogony-like phase, followed by a macrophage-mediated transport of the parasite to the gill, with a final development stage of a spore-laden xenoma within the endothelial and pillar cells. Xenoma rupture triggers a cascade of inflammatory events leading to severe, persistent, and extensive proliferative branchitis. The development of robust and reliable experimental challenge models using several exposure methods in marine and freshwater environments with several fish hosts, is a primary reason for the success of scientific research surrounding L. salmonae. To date, demonstrated factors affecting MGDS transmission include host species, strain and size, the length of contact time between naïve and infected fish, water temperature and flow rates.


Modality and morphology: what we write may not be what we say.
Written language is an evolutionarily recent human invention; consequently, its neural substrates cannot be determined by the genetic code. How, then, does the brain incorporate skills of this type? One possibility is that written language is dependent on evolutionarily older skills, such as spoken language; another is that dedicated substrates develop with expertise. If written language does depend on spoken language, then acquired deficits of spoken and written language should necessarily co-occur. Alternatively, if at least some substrates are dedicated to written language, such deficits may doubly dissociate. We report on 5 individuals with aphasia, documenting a double dissociation in which the production of affixes (e.g., the -ing in jumping) is disrupted in writing but not speaking or vice versa. The findings reveal that written- and spoken-language systems are considerably independent from the standpoint of morpho-orthographic operations. Understanding this independence of the orthographic system in adults has implications for the education and rehabilitation of people with written-language deficits.


Effect of cryotherapy on muscle recovery and inflammation following a bout of damaging exercise.
The purpose of this study was to determine the effect of cryotherapy on the inflammatory response to muscle-damaging exercise using a randomized trial. Twenty recreationally active males completed a 40-min run at a -10 % grade to induce muscle damage. Ten of the subjects were immersed in a 5 °C ice bath for 20 min and the other ten served as controls. Knee extensor peak torque, soreness rating, and thigh circumference were obtained pre- and post-run, and 1, 6, 24, 48, and 72 h post-run. Blood samples were obtained pre- and post-run, and 1, 6 and 24 h post-run for assay of plasma chemokine ligand 2 (CCL2). Peak torque decreased from 270 ± 57 Nm at baseline to 253 ± 65 Nm post-run and increased to 295 ± 68 Nm by 72 h post-run with no differences between groups (p = 0.491). Soreness rating increased from 3.6 ± 6.0 mm out of 100 mm at baseline to 47.4 ± 28.2 mm post-run and remained elevated at all time points with no differences between groups (p = 0.696). CCL2 concentrations increased from 116 ± 31 pg mL(-1) at baseline to 293 ± 109 pg mL(-1) at 6 h post-run (control) and from 100 ± 27 pg mL(-1) at baseline to 208 ± 71 pg mL(-1) at 6 h post-run (cryotherapy). The difference between groups was not significant (p = 0.116), but there was a trend for lower CCL2 in the cryotherapy group at 6 h (p = 0.102), though this measure was highly variable. In conclusion, 20 min of cryotherapy was ineffective in attenuating the strength decrement and soreness seen after muscle-damaging exercise, but may have mitigated the rise in plasma CCL2 concentration. These results do not support the use of cryotherapy during recovery.


Do fixed-dose combination pills or unit-of-use packaging improve adherence? A systematic review.
Adequate adherence to medication regimens is central to the successful treatment of communicable and noncommunicable disease. Fixed-dose combination pills and unit-of-use packaging are therapy-related interventions that are designed to simplify medication regimens and so potentially improve adherence. We conducted a systematic review of relevant randomized trials in order to quantify the effects of fixed-dose combination pills and unit-of-use packaging, compared with medications as usually presented, in terms of adherence to treatment and improved outcomes. Only 15 trials met the inclusion criteria; fixed-dose combination pills were investigated in three of these, while unit-of-use packaging was studied in 12 trials. The trials involved treatments for communicable diseases (n = 5), blood pressure lowering medications (n = 3), diabetic patients (n = 1), vitamin supplementation (n = 1) and management of multiple medications by the elderly (n = 5). The results of the trials suggested that there were trends towards improved adherence and/or clinical outcomes in all but three of the trials; this reached statistical significance in four out of seven trials reporting a clinically relevant or intermediate end-point, and in seven out of thirteen trials reporting medication adherence. Measures of outcome were, however, heterogeneous, and interpretation was further limited by methodological issues, particularly small sample size, short duration and loss to follow-up. Overall, the evidence suggests that fixed-dose combination pills and unit-of-use packaging are likely to improve adherence in a range of settings, but the limitations of the available evidence means that uncertainty remains about the size of these benefits.


Bioreducible hyaluronic acid conjugates as siRNA carrier for tumor targeting.
The successful clinical translation of siRNA-based therapeutics requires efficient carrier systems that can specifically deliver siRNA within the cytosol of the target cells. Although numerous polymeric nanocarriers forming ionic complexes with siRNA have been investigated for cancer therapy, their poor stability and lack of tumor targetability have impeded their in vivo applications. To surmount these limitations, we synthesized a novel type of biodegradable hyaluronic acid-graft-poly(dimethylaminoethyl methacrylate) (HPD) conjugate that can form complexes with siRNA and be chemically crosslinked via the formation of the disulfide bonds under facile conditions. The crosslinked siRNA-HPD (C-siRNA-HPD) complexes exhibited high stability in a 50% serum solution, as compared to the uncrosslinked siRNA-HPD (U-siRNA-HPD) complexes and free siRNA. Both the C-siRNA-HPD and U-siRNA-HPD complexes were efficiently taken up by the CD44-overexpressing melanoma cells (B16F10), but not by the normal fibroblast cells (NIH3T3). When the RFP-expressing B16F10 cells were treated with the complexes or free siRNA, the C-siRNA-HPD complexes showed the highest decrease in RFP expression. In vivo studies demonstrated the selective accumulation of C-siRNA-HPD complexes at the tumor site after their systemic administration into tumor-bearing mice, resulting in an efficient gene silencing effect. Overall, these results suggest that the HPD conjugate could be used as an efficient carrier for the tumor-targeted delivery of siRNA.


Climate Change and Women's Health: Impacts and Opportunities in India.
Climate change impacts on health, including increased exposures to heat, poor air quality, extreme weather events, and altered vector-borne disease transmission, reduced water quality, and decreased food security, affect men and women differently due to biologic, socioeconomic, and cultural factors. In India, where rapid environmental changes are taking place, climate change threatens to widen existing gender-based health disparities. Integration of a gendered perspective into existing climate, development, and disaster-risk reduction policy frameworks can decrease negative health outcomes. Modifying climate risks requires multisector coordination, improvement in data acquisition, monitoring of gender specific targets, and equitable stakeholder engagement. Empowering women as agents of social change can improve mitigation and adaptation policy interventions.


The ingenious mast cell: Contemporary insights into mast cell behavior and function.
Mast cells are (in)famous for their role in allergic diseases, but the physiological and pathophysiological roles of this ingenious cell are still not fully understood. Mast cells are important for homeostasis and surveillance of the human system, recognizing both endogenous and exogenous agents, which induce release of a variety of mediators acting on both immune and non-immune cells, including nerve cells, fibroblasts, endothelial cells, smooth muscle cells, and epithelial cells. During recent years, clinical and experimental studies on human mast cells, as well as experiments using animal models, have resulted in many discoveries that help decipher the function of mast cells in health and disease. In this review, we focus particularly on new insights into mast cell biology, with a focus on mast cell development, recruitment, heterogeneity, and reactivity. We also highlight the development in our understanding of mast cell-driven diseases and discuss the development of novel strategies to treat such conditions.


Lung effector memory and activated CD4+ T cells display enhanced proliferation in surfactant protein A-deficient mice during allergen-mediated inflammation.
Although many studies have shown that pulmonary surfactant protein (SP)-A functions in innate immunity, fewer studies have addressed its role in adaptive immunity and allergic hypersensitivity. We hypothesized that SP-A modulates the phenotype and prevalence of dendritic cells (DCs) and CD4(+) T cells to inhibit Th2-associated inflammatory indices associated with allergen-induced inflammation. In an OVA model of allergic hypersensitivity, SP-A(-/-) mice had greater eosinophilia, Th2-associated cytokine levels, and IgE levels compared with wild-type counterparts. Although both OVA-exposed groups had similar proportions of CD86(+) DCs and Foxp3(+) T regulatory cells, the SP-A(-/-) mice had elevated proportions of CD4(+) activated and effector memory T cells in their lungs compared with wild-type mice. Ex vivo recall stimulation of CD4(+) T cell pools demonstrated that cells from the SP-A(-/-) OVA mice had the greatest proliferative and IL-4-producing capacity, and this capability was attenuated with exogenous SP-A treatment. Additionally, tracking proliferation in vivo demonstrated that CD4(+) activated and effector memory T cells expanded to the greatest extent in the lungs of SP-A(-/-) OVA mice. Taken together, our data suggested that SP-A influences the prevalence, types, and functions of CD4(+) T cells in the lungs during allergic inflammation and that SP deficiency modifies the severity of inflammation in allergic hypersensitivity conditions like asthma.


[Three-dimentional organization of synapses and astroglia in the hippocampus of rats and ground squirrels: new structural and functional paradigms of the synapse function].
The literature data and our own data on the synaptic plasticity and remodeling of synaptic organelles in the central nervous system are reviewed. Modern techniques of laser scanning confocal microscopy and serial thin sectioning for in vivo and in vitro studies of dendritic spines, including the relationship between morphological changes and the efficacy of synaptic transmission, are discussed using, in particular, a model of long-term potentiation. The organization of dendritic spines and postsynaptic densities of different categories as well as the role of filopodia in spine genesis were analyzed. It was shown that the method of serial ultrathin sections is the most effective for unbiased quantitative stereological analysis and 3D reconstructions. By using the refined method of serial ultrathin sections with subsequent three-dimensional reconstructions, the presence of giant mitochondria in hippocampal neuronal dendrites was demonstrated. It was shown that smooth endoplasmic reticulum forms a unified continuum with the outer membrane of the mitochondrial envelope within dendrites. It was suggested that this continuum provides calcium tunneling, which makes possible intracellular signal transduction during synaptic transmission. Evidence is presented indicating the presence of gap junctions ("electrical synapses") in the synapses of mammalian brain, as well as between glial processes, and between glial cells and neurons. Our data and the data of other authors show that glial cell processes form a structural and functional glial network, which modulates the functioning of the neuronal network. The connection of dendritic spines with the glial network is shown on 3D reconstructions by analyzing the neuropil volume in CA1 hippocampal area of ground squirrels in three functional states: normothermia, provoked arousal, and hibernation when brain temperature falls below 6 degrees C. The own data of the authors are discussed indicating the formation of more than five presynaptic boutons (multiple synapses) on both CA1 mushroom-like dendritic spines and CA3 thorny excrescences. On the basis of the analysis, new ideas of the organization and functioning of synapses were suggested.


Effect of Fumigation on Rotylenchulus reniformis Population Density Through Subsurface Drip Irrigation Located Every Other Furrow.
Plots naturally infested with Rotylenchulus reniformis were sampled in the spring of 2006 and 2007 at depths of 15 and 30 cm in the bed, furrow over the drip tape, and "dry" furrow, and at approximately 40 to 45 cm depth in the bed and dry furrow. Then, 1,3-dichloropropene (Telone EC) was injected into the subsurface drip irrigation at 46 kg a.i./ha, and 3 to 4 weeks later the plots were resampled and assayed for nematodes. The transformed values for nematode population density (IvLRr) before fumigation were higher at 30 and 40 cm depths than at a 15 cm depth. IvLRr before fumigation was higher in the soil over the drip lines than in the bed or dry furrow and was higher in the bed than the dry furrow. IvLRr was higher in the plots to be fumigated than the plots that were not to be fumigated for all depths and locations except at a 15 cm depth over the drip lines, where the values were similar. However, after fumigation, IvLRr was lower over the drip lines at a 30 cm depth in plots that were fumigated compared to samples in a similar location and depth that were not fumigated. There were no other location/depth combinations where the fumigation reduced IvLRr below that in the nonfumigated plots. Yield in 2006, which was a very hot and dry year, was predicted adequately (R(2) = 0.67) by a linear model based on the preplant population density of R. reniformis, with a very steep slope (-2.8 kg lint/ha per R. reniformis/100 cm(3) soil). However, no relationship between nematode density and yield was seen in 2007, which had cooler weather for most of the season. Yield was not significantly improved by fumigation through the drip irrigation system in either year compared to plots treated only with aldicarb (0.84 kg a.i./ha), indicating that the level of control with fumigation did not kill enough R. reniformis to be successful.


Role for the ubiquitin-proteasome system in the vacuolar degradation of Ste6p, the a-factor transporter in Saccharomyces cerevisiae.
Ste6p, the a-factor transporter in Saccharomyces cerevisiae, is a multispanning membrane protein with 12 transmembrane spans and two cytosolic ATP binding domains. Ste6p belongs to the ATP binding cassette (ABC) superfamily and provides an excellent model for examining the intracellular trafficking of a complex polytopic membrane protein in yeast. Previous studies have shown that Ste6p undergoes constitutive endocytosis from the plasma membrane, followed by delivery to the vacuole, where it is degraded in a Pep4p-dependent manner, even though only a small portion of Ste6p is exposed to the vacuolar lumen where the Pep4p-dependent proteases reside. Ste6p is known to be ubiquitinated, a modification that may facilitate its endocytosis. In the present study, we further investigated the intracellular trafficking of Ste6p, focusing on the role of the ubiquitin-proteasome machinery in the metabolic degradation of Ste6p. We demonstrate by pulse-chase analysis that the degradation of Ste6p is impaired in mutants that exhibit defects in the activity of the proteasome (doa4 and pre1,2). Likewise, by immunofluorescence, we observe that Ste6p accumulates in the vacuole in the doa4 mutant, as it does in the vacuolar protease-deficient pep4 mutant. One model consistent with our results is that the degradation of Ste6p, the bulk of which is exposed to the cytosol, requires the activity of both the cytosolic proteasomal degradative machinery and the vacuolar lumenal proteases, acting in a synergistic fashion. Alternatively, we discuss a second model whereby the ubiquitin-proteasome system may indirectly influence the Pep4p-dependent vacuolar degradation of Ste6p. This study establishes that Ste6p is distinctive in that two independent degradative systems (the vacuolar Pep4p-dependent proteases and the cytosolic proteasome) are both involved, either directly or indirectly, in the metabolic degradation of a single substrate.


Prediction of anticancer property of bowsellic acid derivatives by quantitative structure activity relationship analysis and molecular docking study.
Boswellic acid consists of a series of pentacyclic triterpene molecules that are produced by the plant Boswellia serrata. The potential applications of Bowsellic acid for treatment of cancer have been focused here. To predict the property of the bowsellic acid derivatives as anticancer compounds by various computational approaches. In this work, all total 65 derivatives of bowsellic acids from the PubChem database were considered for the study. After energy minimization of the ligands various types of molecular descriptors were computed and corresponding two-dimensional quantitative structure activity relationship (QSAR) models were obtained by taking Andrews coefficient as the dependent variable. Different types of comparative analysis were used for QSAR study are multiple linear regression, partial least squares, support vector machines and artificial neural network. From the study geometrical descriptors shows the highest correlation coefficient, which indicates the binding factor of the compound. To evaluate the anticancer property molecular docking study of six selected ligands based on Andrews affinity were performed with nuclear factor-kappa protein kinase (Protein Data Bank ID 4G3D), which is an established therapeutic target for cancers. Along with QSAR study and docking result, it was predicted that bowsellic acid can also be treated as a potential anticancer compound. Along with QSAR study and docking result, it was predicted that bowsellic acid can also be treated as a potential anticancer compound.


First Report of In-Vitro Boscalid-Resistant Isolates of Alternaria solani Causing Early Blight of Potato in Idaho.
Early blight of potato (Solanum tuberosum) is caused by Alternaria solani and occurs annually to some degree in Idaho. The timing of its appearance and rate of disease progress determine the impact on the potato crop. Though losses rarely exceed 20%, they can be higher and occur in stored potatoes if the disease is not controlled. Early blight is managed mainly by cultural practices such as plant nutrition, water management, and avoidance of plant stress, but also with the use of foliar fungicides. Currently, the main fungicides labeled for control of early blight are in the carboxamide and strobilurin fungicide groups. Development of resistance to some fungicide groups may contribute to the loss of control of early blight. Isolates of A. solani from Idaho potatoes were tested for resistance to boscalid in the carboxamide group. Diseased potato leaves with early blight symptoms were collected from fields near Parma, Rupert, and Aberdeen in southern Idaho in 2009 and 2010 and Bonners Ferry in northern Idaho in 2010. To obtain A. solani isolates from leaves, small pieces of leaf tissue (5 × 5 mm) were taken from the center of early blight lesions and streaked across the surface of a thin layer (3 mm) of water agar. Plates were incubated at 25°C overnight to allow spores to germinate. Single germinated A. solani spores were transferred to acidified potato dextrose agar and incubated in the dark at 25°C. Germinated spores were identified based on spore morphology. Spores of A. solani can be easily distinguished from other Alternaria spp. found on potato because they are ellipsoid to oblong and taper to a long beak that is usually as long as the spore body. The identity of cultures grown from single spores was confirmed by colony and spore morphology. Sensitivity of A. solani isolates to boscalid was determined by the spiral gradient endpoint method (2). For all isolates, the effective concentration for 50% reduction in growth was outside the range of the spiral plate dilution series (i.e., isolates were either completely insensitive or completely sensitive to boscalid). In total, 46 isolates (20 collected in 2009 and 26 collected in 2010) were tested against boscalid. Experiments were carried out twice with 2009 isolates using mycelial strips and conidial suspensions. Experiments with 2010 isolates were carried out three times using only conidial suspensions. Of the isolates from 2009, 15% were insensitive. There was no difference between the use of mycelial strips or conidial suspensions. In 2010, 62% of isolates were insensitive. By location, 72% of isolates from Parma, 73% from Rupert, 63% from Aberdeen, and 44% from Bonners Ferry were insensitive. Resistance to boscalid has been reported in A. alternata isolates from pistachio (1,3). However, to our knowledge, this is the first report of resistance to boscalid in isolates of A. solani on potato. These data suggest that resistance to boscalid is widespread in Idaho, even in areas like Bonners Ferry where potato cultivation is limited. Boscalid insensitivity in vitro may not translate directly to commercial production and currently there is no evidence to suggest that boscalid has failed to control early blight in Idaho. However, the discovery of insensitive isolates suggests that boscalid should be considered at high risk of resistance development. References: (1) H. Avenot et al. Plant Dis. 91:1345, 2007. (2) H. Förster et al. Phytopathology 94:163, 2004. (3) N. Rosenzweig et al. (Abstr.) Phytopathology 93(suppl.):S75, 2003.


Dihydroartemisinin-Loaded Chitosan Nanoparticles Inhibit the Rifampicin-Resistant Mycobacterium tuberculosis by Disrupting the Cell Wall.
Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is a deadly infection, and increasing resistance worsens an already bad scenario. In this work, a new nanomedicine antibacterial agent, based on dihydroartemisinin (DHA) and chitosan (CS), has been successfully developed to overcome MTB's drug-resistant. To enhance DHA's solubility, we have prepared nanoparticles of DHA loaded CS by an ionic crosslinking method with sodium tripolyphosphate (STPP) as the crosslinking agent. The DHA-CS nanoparticles (DHA-CS NPs) have been fully characterized by scanning electron microscopy, Fourier transforms infrared spectroscopy, dynamic light scattering, and ultraviolet spectrophotometry. DHA-CS NPs show an excellent antibacterial effect on the rifampicin (RFP)-resistant strain (ATCC 35838) and, at a concentration of 8.0 μg/ml, the antibacterial impact reaches up to 61.0 ± 2.13% (n = 3). The results of Gram staining, acid-fast staining, auramine "O" staining and electron microscopy show that the cell wall of RFP-resistant strains is destroyed by DHA-CS NPs (n = 3), and it is further verified by gas chromatography-mass spectrometry. Since all the metabolites identified in DHA-CS NPs treated RFP-resistant strains indicate an increase in fatty acid synthesis and cell wall repair, it can be concluded that DHA-CS NPs act by disrupting the cell wall. In addition, the resistance of 12 strains is effectively reduced by 8.0 μg/ml DHA-CS NPs combined with RFP, with an effective rate of 66.0%. The obtained results indicate that DHA-CS NPs combined with RFP may have potential use for TB treatment.


Grip and Muscle Strength Dynamometry in Acute Burn Injury: Evaluation of an Updated Assessment Protocol.
External stabilization is reported to improve reliability of hand-held dynamometry, yet this has not been tested in burns. We aimed to assess the reliability of dynamometry using an external system of stabilization in people with moderate burn injury and explore construct validity of strength assessment using dynamometry. Participants were assessed on muscle and grip strength three times on each side. Assessment occurred three times per week for up to 4 weeks. Within-session reliability was assessed using intraclass correlations calculated for within-session data grouped before surgery, immediately after surgery and in the subacute phase of injury. Minimum detectable differences were also calculated. In the same timeframe categories, construct validity was explored using regression analysis incorporating burn severity and demographic characteristics. Thirty-eight participants with total burn surface area 5% to 40% were recruited. Reliability was determined to be clinically applicable for the assessment method (intraclass correlation coefficient >0.75) at all phases after injury. Muscle strength was associated with sex and burn location during injury and wound healing. Burn size in the immediate period after surgery and age in the subacute phase of injury were also associated with muscle strength assessment results. Hand-held dynamometry is a reliable assessment tool for evaluating within-session muscle strength in the acute and subacute phase of injury in burns up to 40% total burn surface area. External stabilization may assist to eliminate reliability issues related to patient and assessor strength.


Blood oxygen level-dependent magnetic resonance imaging in patients with stress-induced angina.
Blood oxygen level-dependent (BOLD) MRI reflects tissue oxygenation and may be useful for the detection of myocardial ischemia in patients with suspected coronary artery disease. We studied 25 patients with stress-induced angina using a T2*-sensitive echo planar imaging sequence before and during adenosine in a single-slice approach. BOLD-MRI results were compared with quantitative angiography and adenosine thallium single-photon emission computed tomography (SPECT). Although image quality was variable because of artifacts, no data were excluded from the analysis. During adenosine, a mean signal intensity decrease was observed for myocardial segments related to coronary stenoses >75%. On average, a nonsignificant increase was observed in the other segments. The angiographically determined stenosis was correlated with BOLD-MRI results. Including all segments and using BOLD-MRI signal intensity increase cutoff value of 1.2%, BOLD-MRI had a sensitivity of 88% and a specificity of 47% to correctly classify severe stenoses. Adenosine thallium SPECT data from distal segments of the same coronary territory were also correlated with BOLD-MRI. However, variability was substantial. In patients with stress-induced angina, adenosine BOLD-MRI detects myocardial ischemia in myocardial segments related to severe coronary stenoses. Its potential will increase with additional improvement of spatial coverage and image quality.


Fitness facilities still lack accessibility for people with disabilities.
Fitness facilities have potential to serve as places of 'health enhancement' for many underserved populations, particularly among people with physical/mobility disabilities where walking outdoors to meet recommendations for regular physical activity is not an option due to mobility or safety issues. To examine the accessibility and usability of fitness facilities across the U.S. from a broader framework of physical and program access. A convenience sample of 227 fitness facilities in 10 states were assessed by trained evaluators using the Accessibility Instrument Measuring Fitness and Recreation Environments (AIMFREE) tool. Non-parametric tests were performed to determine whether AIMFREE section scores were different by geographic region (urban, suburban), business type (nonprofit, for-profit), facility affiliation (fitness center/health club, park district/community center, hospital/rehabilitation facility, university/college), and facility construction date (pre/post passage of the Americans with Disabilities Act, ADA). Raw scores were converted to scaled scores with higher scores indicating better accessibility based on a criterion-referenced approach. Section scale scores (11/13) were low (<70) with differences found across facility affiliation. While facilities built after passage of the ADA had higher accessibility scores compared to pre-ADA facilities, only programs and water fountains had scaled scores ≥70 regardless of facility construction date. There exists a strong and urgent need to encourage owners and operators of fitness facilities to reach a higher level of accessibility. Until then, many people with physical/mobility disabilities will continue to have limited access to programs, equipment, and services offered at these facilities.


An open resource combining multi-contrast MRI and microscopy in the macaque brain.
Understanding brain structure and function often requires combining data across different modalities and scales to link microscale cellular structures to macroscale features of whole brain organisation. Here we introduce the BigMac dataset, a resource combining in vivo MRI, extensive postmortem MRI and multi-contrast microscopy for multimodal characterisation of a single whole macaque brain. The data spans modalities (MRI and microscopy), tissue states (in vivo and postmortem), and four orders of spatial magnitude, from microscopy images with micrometre or sub-micrometre resolution, to MRI signals on the order of millimetres. Crucially, the MRI and microscopy images are carefully co-registered together to facilitate quantitative multimodal analyses. Here we detail the acquisition, curation, and first release of the data, that together make BigMac a unique, openly-disseminated resource available to researchers worldwide. Further, we demonstrate example analyses and opportunities afforded by the data, including improvement of connectivity estimates from ultra-high angular resolution diffusion MRI, neuroanatomical insight provided by polarised light imaging and myelin-stained histology, and the joint analysis of MRI and microscopy data for reconstruction of the microscopy-inspired connectome. All data and code are made openly available.


The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis.
Vitamin D insufficiency is associated with many disorders, leading to calls for widespread supplementation. Some investigators suggest that more clinical trials to test the effect of vitamin D on disorders are needed. We did a trial sequential meta-analysis of existing randomised controlled trials of vitamin D supplements, with or without calcium, to investigate the possible effect of future trials on current knowledge. We estimated the effects of vitamin D supplementation on myocardial infarction or ischaemic heart disease, stroke or cerebrovascular disease, cancer, total fracture, hip fracture, and mortality in trial sequential analyses using a risk reduction threshold of 5% for mortality and 15% for other endpoints. The effect estimate for vitamin D supplementation with or without calcium for myocardial infarction or ischaemic heart disease (nine trials, 48 647 patients), stroke or cerebrovascular disease (eight trials 46 431 patients), cancer (seven trials, 48 167 patients), and total fracture (22 trials, 76 497 patients) lay within the futility boundary, indicating that vitamin D supplementation does not alter the relative risk of any of these endpoints by 15% or more. Vitamin D supplementation alone did not reduce hip fracture by 15% or more (12 trials, 27 834 patients). Vitamin D co-administered with calcium reduced hip fracture in institutionalised individuals (two trials, 3853 patients) but did not alter the relative risk of hip fracture by 15% or more in community-dwelling individuals (seven trials, 46 237 patients). There is uncertainty as to whether vitamin D with or without calcium reduces the risk of death (38 trials, 81 173). Our findings suggest that vitamin D supplementation with or without calcium does not reduce skeletal or non-skeletal outcomes in unselected community-dwelling individuals by more than 15%. Future trials with similar designs are unlikely to alter these conclusions. Health Research Council of New Zealand.


How expert advice influences decision making.
People often use expert advice when making decisions in our society, but how we are influenced by this advice has yet to be understood. To address this, using functional magnetic resonance imaging, we provided expert and novice advice to participants during an estimation task. Participants reported that they valued expert advice more than novice advice, and activity in the ventral striatum correlated with this valuation, even before decisions with the advice were made. When using advice, participants compared their initial opinion to their advisor's opinion. This comparison, termed the "opinion difference", influenced advice utilization and was represented in reward-sensitive brain regions. Finally, the left lateral orbitofrontal cortex integrated both the size of the opinion difference and the advisor's level of expertise, and average activity in this area correlated with mean advice utilization across participants. Taken together, these findings provide neural evidence for how advice engenders behavioral change during the decision-making process.


Low-Lying ππ* States of Heteroaromatic Molecules: A Challenge for Excited State Methods.
The description of low-lying ππ* states of linear acenes by standard electronic structure methods is known to be challenging. Here, we broaden the framework of this problem by considering a set of fused heteroaromatic rings and demonstrate that standard electronic structure methods do not provide a balanced description of the two (typically) lowest singlet state (La and Lb) excitations. While the Lb state is highly sensitive to correlation effects, La suffers from the same drawbacks as charge transfer excitations. We show that the comparison between CIS/CIS(D) can serve as a diagnostic for detecting the two problematic excited states. Standard TD-DFT and even its spin-flip variant lead to inaccurate excitation energies and interstate gaps, with only a double hybrid functional performing somewhat better. The complication inherent to a balanced description of these states is so important that even CC2 and ADC(2) do not necessarily match the ADC(3) reference.


Double-helix enhanced axial localization in STED nanoscopy.
Stimulated Emission Depletion (STED) microscopy enables subdiffraction resolution in the imaging plane. However, STED's lateral improvement in resolution is generally better than the enhancement in the axial direction. Here, we combine conventional STED superresolution imaging with Double Helix Point Spread Function (PSF) modulation for axial localization with a precision better than the classical Rayleigh limit. To demonstrate the capability of the method we resolve in a STED microscope sub-diffraction fluorescent bead assemblies, and localize them axially with better than 25nm precision. We also show that the same setup allows straightforward implementation of wide field phase contrast by imaging larger beads with spiral and dark field phase filtering.


Therapeutic value of oral supplementation with melon superoxide dismutase and wheat gliadin combination.
Dietary antioxidant supplementation has been popular in Western countries. Various supplements have been developed in recent years, and research has been gathered from both animal and clinical research trials. In this review, the therapeutic value of oral administration of a combination of melon superoxide dismutase (SOD) and a vegetable polymer (gliadin) is evaluated. Critical examination of the effects of SOD-gliadin supplementation is carried out, with an emphasis on its impact on oxidative stress levels and on endogenous antioxidant pathways. Overall analysis of peer-reviewed published data suggests that intake of SOD-gliadin might have advantageous health effects. These conclusions are dependent on the condition or pathology under consideration. In general, the authors, who analyzed SOD-gliadin supplementation, support the use of SOD-gliadin supplementation as a complementary treatment rather than a therapeutic treatment. To further clarify the importance of dietary SOD-gliadin administration, additional large-scale clinical trials are recommended.


Utilization of a one-dimensional score for surveying chemical-induced changes in expression levels of multiple biomarker gene sets using a large-scale toxicogenomics database.
A large-scale toxicogenomcis database has now been constructed in the Toxicogenomics Project in Japan (TGP). To facilitate the analytical procedures for such large-scale microarray data, we developed a simple one-dimensional score, named TGP1 which expresses the trend of the changes in expression of biomarker genes as a whole. To evaluate the usefulness of the TGP1 score, microarray data of rat liver and rat hepatocytes deposited in the TGP database were scored for three biomarker gene sets, i.e., carcinogenesis-related, PPARalpha-regulated and glutathione depletion-related gene sets. The TGP1 scoring system gave reasonable results, i.e., the scores for carcinogenesis-related genes were high in omeprazole-, chlorpromazine-, hexachlorobenzene-, sulfasalazine- and Wy-14,643-treated rat livers, that for PPARalpha-regulated genes were high in clofibrate-, Wy-14,643-, gemfibrozil-, benzbromarone- and aspirin-treated rat livers as well as rat hepatocytes, and for glutathione deficiency-related genes were high in omeprazole-, bromobenzene-, acetaminophen- and coumarin-treated rat liver. We concluded that the TGP1 score is useful for surveying the expression changes in multiple biomarker gene sets for a large-scale toxicogenomics database, which would reduce the time of doing conventional multivariate statistical analysis. In addition, the TGP1 score can be applied to screening of compatible biomarker gene sets between rat liver and rat hepatocytes, like PPARalpha-regulated gene sets, which will allow us to develop an appropriate in vitro system for drug safety assessment in vivo.


Sirtuin 1 inhibition delays cyst formation in autosomal-dominant polycystic kidney disease.
Autosomal-dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2 and is characterized by the development of multiple bilateral renal cysts that replace normal kidney tissue. Here, we used Pkd1 mutant mouse models to demonstrate that the nicotinamide adenine dinucleotide-dependent (NAD-dependent) protein deacetylase sirtuin 1 (SIRT1) is involved in the pathophysiology of ADPKD. SIRT1 was upregulated through c-MYC in embryonic and postnatal Pkd1-mutant mouse renal epithelial cells and tissues and could be induced by TNF-α, which is present in cyst fluid during cyst development. Double conditional knockouts of Pkd1 and Sirt1 demonstrated delayed renal cyst formation in postnatal mouse kidneys compared with mice with single conditional knockout of Pkd1. Furthermore, treatment with a pan-sirtuin inhibitor (nicotinamide) or a SIRT1-specific inhibitor (EX-527) delayed cyst growth in Pkd1 knockout mouse embryonic kidneys, Pkd1 conditional knockout postnatal kidneys, and Pkd1 hypomorphic kidneys. Increased SIRT1 expression in Pkd1 mutant renal epithelial cells regulated cystic epithelial cell proliferation through deacetylation and phosphorylation of Rb and regulated cystic epithelial cell death through deacetylation of p53. This newly identified role of SIRT1 signaling in cystic renal epithelial cells provides the opportunity to develop unique therapeutic strategies for ADPKD.


Impacts of climate warming on vegetation in Qaidam Area from 1990 to 2003.
The observed warming trend in the Qaidam area, an arid basin surrounded by high mountains, has caused land surface dynamics that are detectable using remotely sensed data. In this paper, we detected land-cover changes in the Qaidam Area between 1990 and 2003 in attempt to depict its spatial variability. The land-cover changes were categorized into two trends: degradation and amelioration, and their spatial patterns were examined. Then we estimated the correlation coefficients between growing-season NDVI and several climatic factors with the consideration of duration and lagging effects. The results show that the inter-annual NDVI variations are positively correlated with May to July precipitations, but not significantly correlated with sunshine duration. We observed no obvious trend in precipitation or sunshine duration from 1990 to 2003. Thus, the authors suggest that their slight fluctuations may not be responsible to the decade-scaled land-cover changes. However, our results indicate a good positive relationship between the NDVI trend and climate warming in the ameliorated areas, but a negative one in the degraded areas. By statistical analyses, we found that degradations mainly occurred at the oasis boundaries and at lower elevations in the non-oasis regions where effective soil moisture might have been reduced by the warming-caused increase in evapotranspiration. At higher elevations where thermal condition acts as a major limiting factor, ameliorations were unequivocally detected, which is attributable to the direct facilitation by temperature increases. We suggest that the impacts of the observed climate warming on vegetation are spatially heterogeneous, depending on the combinations of thermal condition and moisture availability.


Receptor-mediated endocytosis of particles by peripheral dendritic cells.
Human peripheral dendritic cells (DCs) are antigen-presenting cells with the ability to internalize antigen and present antigen-derived peptides to T cells. Human DCs express several receptors on the surface for endocytosis and other recognition receptors that bind to microbes or microbial products, which are internalized and processed. Here, we report the use of nanometer-size zeolite particles as a tool to study receptor-mediated endocytosis by the two subsets of immature DCs, myeloid (mDC) and plasmacytoid (pDC) dendritic cells. A major difference in receptor-mediated endocytosis was observed between the two populations of peripheral DCs. The pDC population demonstrated an almost complete lack of receptor-mediated endocytosis of zeolite particles, whereas the mDC population demonstrated a clear receptor-mediated endocytosis. Fc receptors are expressed by both peripheral DC populations and lipoteichoic acid (LTA) and lipopolysaccharide (LPS) are known ligands of the Toll-like receptor (TLR)-2 and TLR4, respectively, both TLRs expressed by human mDCs. An efficient receptor-mediated endocytosis of immunoglobulin G-, LTA-, and LPS-coated zeolite particles was observed by the mDC population and their endocytosing capacity depended strongly on the density of the ligand adsorbed onto the zeolite particles. In conclusion, an efficient receptor-mediated endocytosis was observed from the mDC population, whereas the pDCs demonstrated an almost complete lack of receptor-mediated endocytosis and nanometer-size dealuminated zeolite particles were a useful tool for studying receptor-mediated endocytosis in human peripheral DCs.


Medical emergency department utilization patterns among uninsured patients with psychiatric disorders.
This study examined medical emergency department utilization for patterns among uninsured patients with psychiatric disorders. Billing records of 15,672 uninsured adult patients treated in the emergency department of an academic medical center in southeast Texas over a 12-month period were analyzed for information on demographic characteristics, diagnosis, number of emergency department visits, and hospitalization. Overall, 11.8% of the population was diagnosed as having at least one psychiatric disorder during an emergency department visit. Patients with psychiatric disorders had an increased risk of having multiple emergency department visits and hospitalization compared with patients without psychiatric disorders. The risk of multiple emergency department visits was particularly high for patients with either bipolar disorder or psychotic disorders. Uninsured patients with psychiatric disorders appear to be heavy users of medical emergency department services. These findings may be helpful in developing more efficient strategies to serve the mental health needs of the uninsured.


Systematic Mendelian randomization framework elucidates hundreds of CpG sites which may mediate the influence of genetic variants on disease.
We have undertaken a systematic Mendelian randomization (MR) study using methylation quantitative trait loci (meQTL) as genetic instruments to assess the relationship between genetic variation, DNA methylation and 139 complex traits. Using two-sample MR, we identified 1148 associations across 61 traits where genetic variants were associated with both proximal DNA methylation (i.e. cis-meQTL) and complex trait variation (P < 1.39 × 10-08). Joint likelihood mapping provided evidence that the genetic variant which influenced DNA methylation levels for 348 of these associations across 47 traits was also responsible for variation in complex traits. These associations showed a high rate of replication in the BIOS QTL and UK Biobank datasets for 14 selected traits, as 101 of the attempted 128 associations survived multiple testing corrections (P < 3.91 × 10-04). Integrating expression quantitative trait loci (eQTL) data suggested that genetic variants responsible for 306 of the 348 refined meQTL associations also influence gene expression, which indicates a coordinated system of effects that are consistent with causality. CpG sites were enriched for histone mark peaks in tissue types relevant to their associated trait and implicated genes were enriched across relevant biological pathways. Though we are unable to distinguish mediation from horizontal pleiotropy in these analyses, our findings should prove valuable in prioritizing candidate loci where DNA methylation may influence traits and help develop mechanistic insight into the aetiology of complex disease.


Reverse Differentiation via Predictive Coding.
Deep learning has redefined AI thanks to the rise of artificial neural networks, which are inspired by neuronal networks in the brain. Through the years, these interactions between AI and neuroscience have brought immense benefits to both fields, allowing neural networks to be used in a plethora of applications. Neural networks use an efficient implementation of reverse differentiation, called backpropagation (BP). This algorithm, however, is often criticized for its biological implausibility (e.g., lack of local update rules for the parameters). Therefore, biologically plausible learning methods that rely on predictive coding (PC), a framework for describing information processing in the brain, are increasingly studied. Recent works prove that these methods can approximate BP up to a certain margin on multilayer perceptrons (MLPs), and asymptotically on any other complex model, and that zerodivergence inference learning (Z-IL), a variant of PC, is able to exactly implement BP on MLPs. However, the recent literature shows also that there is no biologically plausible method yet that can exactly replicate the weight update of BP on complex models. To fill this gap, in this paper, we generalize (PC and) Z-IL by directly defining it on computational graphs, and show that it can perform exact reverse differentiation. What results is the first PC (and so biologically plausible) algorithm that is equivalent to BP in the way of updating parameters on any neural network, providing a bridge between the interdisciplinary research of neuroscience and deep learning. Furthermore, the above results in particular also immediately provide a novel local and parallel implementation of BP.


Distributed compact plasma reactor decontamination for planetary protection in space missions.
This paper presents a proof-of-concept study establishing effectiveness of the Active Plasma Sterilizer (APS) for decontamination in planetary protection. The APS uses Compact Portable Plasma Reactors (CPPRs) to produce surface dielectric barrier discharge, a type of cold plasma, using ambient air to generate and distribute reactive species like ozone used for decontamination. Decontamination tests were performed with pathogenic bacteria (Escherichia coli and Bacillus subtilis) on materials (Aluminum, Polycarbonate, Kevlar and Orthofabric) relevant to space missions. Results show that the APS can achieve 4 to 5 log reductions of pathogenic bacteria on four selected materials, simultaneously at 11 points within 30 min, using power of 13.2 ± 2.22 W. Spatial decontamination data shows the APS can uniformly sterilize several areas of a contaminated surface within 30 min. Ozone penetration through Kevlar and Orthofabric layers was achieved using the CPPR with no external agent assisting penetration. Preliminary material compatibility tests with SEM analysis of the APS exposed materials showed no significant material damage. Thus, this study shows the potential of the APS as a light-weight sustainable decontamination technology for planetary protection with advantages of uniform spatial decontamination, low processing temperatures, low exposure times, material compatibility and the ability to disinfect porous surfaces.


Competitive Supramolecular Associations Mediate the Viscoelasticity of Binary Hydrogels.
Supramolecular polymers are known to form strong and resilient hydrogels which can take up large amounts of water while exhibiting ease of processing and self-healing. They also possess similarities with networks of biological macromolecules. The combination of these features makes supramolecular polymers ideal candidates for studying mechanisms and consequences of self-assembly, which are relevant to biological materials. At the same time, this renders investigations of mixed hydrogels based on different supramolecular compounds necessary, since this substantially widens their applicability. Here, we address unusual viscoelastic properties of a class of binary hydrogels made by mixing fibrillar supramolecular polymers that are formed from two compounds: 1,3,5-benzene-tricarboxamide decorated with aliphatic chains terminated by tetra(ethylene glycol) (BTA) and a 20 kg/mol telechelic poly(ethylene glycol) decorated with the same hydrogen bonding BTA motif on both ends (BTA-PEG-BTA). Using a suite of experimental and simulation techniques, we find that the respective single-compound-based supramolecular systems form very different networks which exhibit drastically different rheology. More strikingly, mixing the compounds results in a non-monotonic dependence of modulus and viscosity on composition, suggesting a competition between interactions of the two compounds, which can then be used to fine-tune the mechanical properties. Simulations offer insight into the nature of this competition and their remarkable qualitative agreement with the experimental results is promising for the design of mixed hydrogels with desired and tunable properties. Their combination with a sensitive dynamic probe (here rheology) offer a powerful toolbox to explore the unique properties of binary hydrogel mixtures.


Knowledge-guided multi-scale independent component analysis for biomarker identification.
Many statistical methods have been proposed to identify disease biomarkers from gene expression profiles. However, from gene expression profile data alone, statistical methods often fail to identify biologically meaningful biomarkers related to a specific disease under study. In this paper, we develop a novel strategy, namely knowledge-guided multi-scale independent component analysis (ICA), to first infer regulatory signals and then identify biologically relevant biomarkers from microarray data. Since gene expression levels reflect the joint effect of several underlying biological functions, disease-specific biomarkers may be involved in several distinct biological functions. To identify disease-specific biomarkers that provide unique mechanistic insights, a meta-data "knowledge gene pool" (KGP) is first constructed from multiple data sources to provide important information on the likely functions (such as gene ontology information) and regulatory events (such as promoter responsive elements) associated with potential genes of interest. The gene expression and biological meta data associated with the members of the KGP can then be used to guide subsequent analysis. ICA is then applied to multi-scale gene clusters to reveal regulatory modes reflecting the underlying biological mechanisms. Finally disease-specific biomarkers are extracted by their weighted connectivity scores associated with the extracted regulatory modes. A statistical significance test is used to evaluate the significance of transcription factor enrichment for the extracted gene set based on motif information. We applied the proposed method to yeast cell cycle microarray data and Rsf-1-induced ovarian cancer microarray data. The results show that our knowledge-guided ICA approach can extract biologically meaningful regulatory modes and outperform several baseline methods for biomarker identification. We have proposed a novel method, namely knowledge-guided multi-scale ICA, to identify disease-specific biomarkers. The goal is to infer knowledge-relevant regulatory signals and then identify corresponding biomarkers through a multi-scale strategy. The approach has been successfully applied to two expression profiling experiments to demonstrate its improved performance in extracting biologically meaningful and disease-related biomarkers. More importantly, the proposed approach shows promising results to infer novel biomarkers for ovarian cancer and extend current knowledge.


Ontological differences in first compared to third trimester human fetal placental chorionic stem cells.
Human mesenchymal stromal/stem cells (MSC) isolated from fetal tissues hold promise for use in tissue engineering applications and cell-based therapies, but their collection is restricted ethically and technically. In contrast, the placenta is a potential source of readily-obtainable stem cells throughout pregnancy. In fetal tissues, early gestational stem cells are known to have advantageous characteristics over neonatal and adult stem cells. Accordingly, we investigated whether early fetal placental chorionic stem cells (e-CSC) were physiologically superior to their late gestation fetal chorionic counterparts (l-CSC). We showed that e-CSC shared a common phenotype with l-CSC, differentiating down the osteogenic, adipogenic and neurogenic pathways, and containing a subset of cells endogenously expressing NANOG, SOX2, c-MYC, and KLF4, as well as an array of genes expressed in pluripotent stem cells and primordial germ cells, including CD24, NANOG, SSEA4, SSEA3, TRA-1-60, TRA-1-81, STELLA, FRAGILIS, NANOS3, DAZL and SSEA1. However, we showed that e-CSC have characteristics of an earlier state of stemness compared to l-CSC, such as smaller size, faster kinetics, uniquely expressing OCT4A variant 1 and showing higher levels of expression of NANOG, SOX2, c-MYC and KLF4 than l-CSC. Furthermore e-CSC, but not l-CSC, formed embryoid bodies containing cells from the three germ layer lineages. Finally, we showed that e-CSC demonstrate higher tissue repair in vivo; when transplanted in the osteogenesis imperfecta mice, e-CSC, but not l-CSC increased bone quality and plasticity; and when applied to a skin wound, e-CSC, but not l-CSC, accelerated healing compared to controls. Our results provide insight into the ontogeny of the stemness phenotype during fetal development and suggest that the more primitive characteristics of early compared to late gestation fetal chorionic stem cells may be translationally advantageous.


Lipid metabolism in women.
Differences in whole-body lipid metabolism between men and women are indicated by lower-body fat accumulation in women but more marked accumulation of fat in the intra-abdominal visceral fat depots of men. Circulating blood lipid concentrations also show gender-related differences. These differences are most marked in premenopausal women, in whom total cholesterol, LDL-cholesterol and triacylglycerol concentrations are lower and HDL-cholesterol concentration is higher than in men. Tendency to accumulate body fat in intra-abdominal fat stores is linked to increased risk of CVD, metabolic syndrome, diabetes and other insulin-resistant states. Differential regional regulation of adipose tissue lipolysis and lipogenesis must underlie gender-related differences in the tendency to accumulate fat in specific fat depots. However, empirical data to support current hypotheses remain limited at the present time because of the demanding and specialist nature of the methods used to study adipose tissue metabolism in human subjects. In vitro and in vivo data show greater lipolytic sensitivity of abdominal subcutaneous fat and lesser lipolytic sensitivity of femoral and gluteal subcutaneous fat in women than in men. These differences appear to be due to fewer inhibitory alpha adrenergic receptors in abdominal regions and greater alpha adrenergic receptors in gluteal and femoral regions in women than in men. There do not appear to be major gender-related differences in rates of fatty acid uptake (lipogenesis) in different subcutaneous adipose tissue regions. In visceral fat rates of both lipolysis and lipogenesis appear to be greater in men than in women; higher rates of lipolysis may be due to fewer alpha adrenergic receptors in this fat depot in men. Fatty acid uptake into this depot in the postprandial period is approximately 7-fold higher in men than in women. Triacylglycerol concentrations appear to be a stronger cardiovascular risk factor in women than in men, with particular implications for cardiovascular risk in diabetic women. The increased triacylglycerol concentrations observed in women taking hormone-replacement therapy (HRT) may explain the paradoxical findings of increased rates of CVD in women taking HRT that have been reported from recent primary and secondary prevention trials of HRT.


Global biomass production potentials exceed expected future demand without the need for cropland expansion.
Global biomass demand is expected to roughly double between 2005 and 2050. Current studies suggest that agricultural intensification through optimally managed crops on today's cropland alone is insufficient to satisfy future demand. In practice though, improving crop growth management through better technology and knowledge almost inevitably goes along with (1) improving farm management with increased cropping intensity and more annual harvests where feasible and (2) an economically more efficient spatial allocation of crops which maximizes farmers' profit. By explicitly considering these two factors we show that, without expansion of cropland, today's global biomass potentials substantially exceed previous estimates and even 2050s' demands. We attribute 39% increase in estimated global production potentials to increasing cropping intensities and 30% to the spatial reallocation of crops to their profit-maximizing locations. The additional potentials would make cropland expansion redundant. Their geographic distribution points at possible hotspots for future intensification.


Tandem duplications lead to novel expression patterns through exon shuffling in Drosophila yakuba.
One common hypothesis to explain the impacts of tandem duplications is that whole gene duplications commonly produce additive changes in gene expression due to copy number changes. Here, we use genome wide RNA-seq data from a population sample of Drosophila yakuba to test this 'gene dosage' hypothesis. We observe little evidence of expression changes in response to whole transcript duplication capturing 5' and 3' UTRs. Among whole gene duplications, we observe evidence that dosage sharing across copies is likely to be common. The lack of expression changes after whole gene duplication suggests that the majority of genes are subject to tight regulatory control and therefore not sensitive to changes in gene copy number. Rather, we observe changes in expression level due to both shuffling of regulatory elements and the creation of chimeric structures via tandem duplication. Additionally, we observe 30 de novo gene structures arising from tandem duplications, 23 of which form with expression in the testes. Thus, the value of tandem duplications is likely to be more intricate than simple changes in gene dosage. The common regulatory effects from chimeric gene formation after tandem duplication may explain their contribution to genome evolution.


Reanalyzing the 1900-1920 sleeping sickness epidemic in Uganda.
Sleeping sickness has long been a major public health problem in Uganda. From 1900 to 1920, more than 250,000 people died in an epidemic that affected the southern part of the country, particularly the Busoga region. The epidemic has traditionally been ascribed to Trypanosoma brucei gambiense, a parasite now confined to central and western Africa. The Busoga region still reports sleeping sickness, although it is caused by T.b. rhodesiense, commonly believed to have spread to Uganda from Zambia in the 1940s. Our analysis of clinical data recorded in the early 1900s shows that the clinical course of sleeping sickness cases during the 1900-1920 epidemic in Uganda was markedly different from T.b. gambiense cases, but similar to T.b. rhodesiense. These findings suggest that T.b. rhodesiense was present in Uganda and contributed to the epidemic. The historic context is reassessed in the light of these data.


Optogenetic Activation of A11 Region Increases Motor Activity.
Limbic brain regions drive goal-directed behaviors. These behaviors often require dynamic motor responses, but the functional connectome of limbic structures in the diencephalon that control locomotion is not well known. The A11 region, within the posterior diencephalon has been postulated to contribute to motor function and control of pain. Here we show that the A11 region initiates movement. Photostimulation of channelrhodopsin 2 (ChR2) transfected neurons in A11 slice preparations showed that neurons could follow stimulation at frequencies of 20 Hz. Our data show that photostimulation of ChR2 transfected neurons in the A11 region enhances motor activity often leading to locomotion. Using vGluT2-reporter and vGAT-reporter mice we show that the A11 tyrosine hydroxylase positive (TH) dopaminergic neurons are vGluT2 and vGAT negative. We find that in addition to dopaminergic neurons within the A11 region, there is another neuronal subtype which expresses the monoenzymatic aromatic L-amino acid decarboxylase (AADC), but not TH, a key enzyme involved in the synthesis of catecholamines including dopamine. This monoaminergic-based motor circuit may be involved in the control of motor behavior as part of a broader diencephalic motor region.


Difference of Helicobacter pylori colonization in recurrent inflammatory and simple hyperplastic tonsil tissues.
To investigate the difference in colonization by Helicobacter pylori between recurrent inflammatory and normal hyperplastic human palatine tonsil tissues. A retrospective review of a prospective data set. Tertiary referral center. Patients undergoing tonsillectomy for a variety of reasons had routine screening for H pylori. Medical records of all patients who underwent tonsillectomy were reviewed to identify (1) indications for surgery and (2) presence or absence of H pylori in the specimen. All medical records that had information on H pylori were included. Patients were divided into the following 2 groups: those having tonsillectomy for chronic recurrent tonsillitis and those having tonsillectomy for sleep-related breathing disorders (SRBDs) with no recent history of tonsillitis. There were 44 patients in the tonsillitis group (18 women and 26 men; mean age, 28.6 years) and 50 patients in the SRBD group (11 women and 39 men; mean age, 33.6 years). Of 94 patients the Pronto Dry test results were positive in 33 (35%) and negative in 61 (65%). The H pylori positive rates in the tonsillitis and SRBD groups were 48% (21 of 44) and 24% (12 of 50), respectively (P < .001). Helicobacter pylori can colonize in human palatine tonsil tissues. A significantly higher positive H pylori rate was present in the tonsillitis group (48%) compared with the SRBD group (24%). Based on this finding, future studies should be performed to elucidate whether eradication therapy for H pylori is effective in decreasing recurrent inflammation of human palatine tonsils.


Meal frequency and vegetable intake does not predict the development of frailty in older adults.
Frailty is considered highly prevalent among the aging population. Fruit and vegetable intake is associated with positive health outcomes across the life-span; however, the relationship with health benefits among older adults has received little attention. The aim was to examine if a relationship exists between meal frequency or frequency of vegetable intake and the development of frailty in a population of older adults. A total of 371 individuals, 80 years or older, from the study 'Elderly Persons in the Risk Zone' were included. Data was collected in the participants' home by face-to-face interviews up to 24 months after the intervention. Baseline data were calculated using Chi2-test; statistical significance was accepted at the 5% level. Binary logistic regression was used for the relationship between meal frequency or vegetable intake and frailty. Mean meal frequency was 4.2 ± 0.9 meals per day; women seem to have a somewhat higher meal frequency than men (p=0.02); 57% of the participants had vegetables with at least one meal per day. No significant relationship was found between meal frequency or vegetable intake and frailty at 12 or 24 months follow-ups. Among this group of older adults (80+), meal frequency was slightly higher among women than men, and just over half of the participants had vegetables with at least one meal a day. The risk of developing frailty was not associated with meal frequency or vegetable intake. The questions in this study were meant as indicators for healthy food habits.


Cochlear implants as a treatment option for unilateral hearing loss, severe tinnitus and hyperacusis.
Tinnitus is an incapacitating condition commonly affecting cochlear implant (CI) candidates. The aim of this clinical study is to assess the long-term effects of CI treatment in patients with severe-to-profound, sensorineural, unilateral hearing loss (UHL) and incapacitating tinnitus. We performed a prospective Cochlear™ company-sponsored multicentre study in five Spanish centres. Sixteen patients with UHL and incapacitating tinnitus, which was indicated by a Tinnitus Handicap Inventory (THI) score >58%, received a Nucleus® CI in their deaf ear. The study design includes repeated within-subject measures on hearing, tinnitus, hyperacusis and quality of life up to 12 months after initial CI fitting. In addition to hearing loss and tinnitus, all patients suffered from hyperacusis. Most patients had a sudden hearing loss and received a CI within 2 years after their hearing loss. Preliminary 6-month, post-CI activation data of 13 subjects showed that the majority of patients perceived a subjective benefit from CI treatment, which was assessed using the THI, a Visual Analogue Scale of tinnitus loudness/annoyance and the Speech, Spatial and Qualities of Hearing Scale. Preliminary 12-month data of 7 subjects showed that most patients also perceived a degree of relief from their hyperacusis. One patient showed no improvements in any of the applied scales, which could be explained by partial insertion of the electrode due to obstruction of the cochlea by otosclerosis. In conclusion, CI can successfully be used in the treatment of UHL patients with accompanying severe tinnitus and hyperacusis. Implantation resulted in hearing benefits and a durable relief from tinnitus and hyperacusis in the majority of patients. These findings support the hypothesis that pathophysiological mechanisms after peripheral sensorineural hearing loss are at least partly reversible when hearing is restored with a CI.


Becoming a role model: the breastfeeding trajectory of Hong Kong women breastfeeding longer than 6 months.
While a substantial proportion of breastfeeding women stop early in the postpartum period, some women are able to breastfeed for longer periods. The aim of this research was to explore the experience of breastfeeding with a subsample of Hong Kong women who have breastfed for longer than 6 months. Participants (n=17) were recruited from a larger infant-feeding study (n=360) conducted in tertiary-care hospitals in Hong Kong. In-depth qualitative interviews were conducted and content analysis was used to analyse the data. Data analysis revealed four themes that encompassed the women's experiences: (1) making the decision, (2) maintaining family harmony, (3) overcoming barriers, and (4) sustaining lactation. Antenatally, participants anticipated that breastfeeding would be very 'difficult' and described how the practice did not fit with the image of a professional woman in Hong Kong. Despite family opposition, frequently from their mother-in-law, and lack of societal acceptance, difficulties were overcome by what the Chinese people call hung-sum or determination. This study highlights unique cultural and social findings affecting breastfeeding women in Hong Kong which may be useful to health-care providers working with Chinese women locally and internationally.


Survival of ileal pouch anal anastomosis constructed after colectomy or secondary to a previous ileorectal anastomosis in ulcerative colitis patients: a population-based cohort study.
Ileorectal anastomosis (IRA) affects bowel function, sexual function and reproduction less negatively than ileal pouch anal anastomosis (IPAA), the standard reconstruction after colectomy for ulcerative colitis (UC). In younger UC patients, IRA may have a role postponing pelvic surgery and IPAA. The aim of the present study was to investigate the survival of IPAA secondary to IRA compared to IPAA as primary reconstruction, as this has not previously been studied in UC. All patients with UC diagnosis between 1960 and 2010 in Sweden were identified from the National Patient Registry. From this cohort, colectomized patients reconstructed with primary IPAA and patients reconstructed with IPAA secondary to IRA were identified. The survival of the IPAA was followed up until pouch failure, defined as pouchectomy and ileostomy or a diverting ileostomy alone. Out of 63,796 patients, 1796 were reconstructed with IPAA, either primarily (n = 1720) or secondary to a previous IRA (n = 76). There were no demographic differences between the groups, including length of follow-up (median 12.6 (IQR 6.7-16.6) years and 10.0 (IQR 3.5-15.9) years, respectively). Failure of the IPAA occurred in 103 (6.0%) patients with primary and in 6 (8%) patients after secondary IPAA (P = 0.38 log-rank). The 10-year pouch survival was 94% (95% CI 93-96) for primary IPAA and 92% (81-97) for secondary. Patients choosing IRA as primary reconstruction do not have an increased risk of failure of a later secondary IPAA in comparison with patients with primary IPAA.


Urban-Rural Partnership Framework to Enhance Food-Energy-Water Security in the Post-COVID-19 Era.
Food, energy, and water (collectively referred to as 'FEW') security forms the key to human survival as well as socioeconomic development. However, the security of these basic resources is increasingly threatened due to growing demand. Beyond the widespread implications on public health, Coronavirus disease (COVID-19) has further raised additional challenges for FEW security, particularly for urban populations, as they mainly outsource their FEW demands from rural areas outside their physical boundaries. In light of that, this study reviews existing literature on FEW security to highlight the growing relevance of urban-rural linkages for realizing FEW security, especially against the backdrop of the COVID-19 pandemic. To achieve this, relevant research documents have been identified through Elsevier's Scopus database and other sources (by applying search equations). The authors have accordingly underlined the necessity of shifting the conventional urban-centric approach to city region-centric development planning for the post-COVID-19 era. To this end, a framework has been suggested for translating physical urban-rural linkages to a partnership enhancing a collective response. The major elements of this framework are the conceptualization of national-level policies to support urban-rural linkages. The framework can play the role of a science-policy-action interface to redesign the FEW system in city regions.


Complement factor P is a ligand for the natural killer cell-activating receptor NKp46.
Innate lymphoid cells (ILCs) are involved in immune responses to microbes and various stressed cells, such as tumor cells. They include group 1 [such as natural killer (NK) cells and ILC1], group 2, and group 3 ILCs. Besides their capacity to respond to cytokines, ILCs detect their targets through a series of cell surface-activating receptors recognizing microbial and nonmicrobial ligands. The nature of some of these ligands remains unclear, limiting our understanding of ILC biology. We focused on NKp46, which is highly conserved in mammals and expressed by all mature NK cells and subsets of ILC1 and ILC3. We show here that NKp46 binds to a soluble plasma glycoprotein, the complement factor P (CFP; properdin), the only known positive regulator of the alternative complement pathway. Consistent with the selective predisposition of patients lacking CFP to lethal Neisseria meningitidis (Nm) infections, NKp46 and group 1 ILCs bearing this receptor were found to be required for mice to survive Nm infection. Moreover, the beneficial effects of CFP treatment for Nm infection were dependent on NKp46 and group 1 NKp46+ ILCs. Thus, group 1 NKp46+ ILCs interact with the complement pathway, via NKp46, revealing a cross-talk between two partners of innate immunity in the response to an invasive bacterial infection.


Cell Death Pathways in Lymphoid Malignancies.
This review highlights the importance of the Bcl-2 family members in lymphoma cell survival and discusses the approaches to modulate their function, directly or indirectly, to advance lymphoma therapeutics. The balance of cell death versus survival is ultimately leveraged at the mitochondria. Mitochondrial outer membrane permeabilization (MOMP) is the critical event that governs the release of pro-apoptotic molecules from the intermembrane mitochondrial space. MOMP is achieved through the coordinated actions of pro- and anti-apoptotic Bcl-2 family member proteins. Recognition of functional alterations among the Bcl-2 family member proteins led to identification of tractable targets to combat hematologic malignancies. A new class of drugs, termed BH3 mimetics, was introduced in the clinic. Venetoclax, a Bcl-2 inhibitor, received regulatory approvals in therapy of chronic lymphocytic leukemia and acute myeloid leukemia. Alternative pro-survival Bcl-2 family proteins, in particular Mcl-1, have been successfully targeted in preclinical studies using novel-specific BH3 mimetics. Finally, anti-apoptotic Bcl-2 family members may be targeted indirectly, via interference with the pro-survival signaling pathways, e.g., phosphoinotiside-3 kinase, B-cell receptor signaling, and NF-κB.


Action of the e locus of mice in the response of phaeomelanic hair follicles to alpha-melanocyte-stimulating hormone in vitro.
Dibutyryl adenosine 3',5'-monophosphate (dibutyryl cyclic AMP) induced eumelanin synthesis in hair bulb melanocytes of recessive yellow (e/e) mice in vitro, whereas alpha-melanocyte-stimulating hormone (alpha-MSH) did not. In contrast, the melanocytes of lethal yellow (Ay/a) mice produced eumelanin in response to both dibutyryl cyclic AMP and alpha-MSH. These results suggest that the e locus controls a mechanism that determines the function of an alpha-MSH receptor.


Impulse control disorder in patients with Parkinson's disease under dopamine agonist therapy: a multicentre study.
Impulse control disorders (ICDs) encompass a wide spectrum of abnormal behaviour frequently found in cases of Parkinson's disease (PD) treated with dopamine agonists (DAs). The main aim of this study was to analyse ICD prevalence with different DAs. We carried out a multicentre transversal study to evaluate the presence of ICDs in patients with PD chronically treated (>6 months) with a single non-ergolinic DA (pramipexole, ropinirole, or rotigotine). Clinical assessment of ICD was performed using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease. Thirty-nine per cent of patients (91/233) fulfilled the clinical criteria for ICD. The group of patients with ICD symptoms (ICD+) differed from those without ICD symptoms (ICD-) in younger age and type of DA intake. Oral DA treatment (pramipexole and ropinirole) was associated with higher risk of ICDs compared with transdermal DA (rotigotine): 84/197 (42%) patients treated with oral DA developed ICD, versus 7/36 (19%) patients treated with transdermal DA (Fisher's exact text <0.01). In univariate analysis, a younger age (p<0.01), treatment with rasagiline (p<0.05), and especially treatment with an oral DA (pramipexole or ropinirole) (p<0.01) were significantly associated with ICD. Multivariate analysis confirmed that oral DA remained significantly associated with ICD (p: 0.014, OR: 3.14; 1.26-7.83). ICD was significantly associated with the use of the non-ergolinic oral DA (pramipexole and ropinirole) when compared with transdermal non-ergolinic DA (rotigotine). Since pramipexole, ropinirole and rotigotine are non-ergolinic DAs with very similar pharmacodynamic profiles, it is likely that other factors including route of administration (transdermal vs oral) explain the difference in risk of ICD development.


Proteostasis and RNA Binding Proteins in Synaptic Plasticity and in the Pathogenesis of Neuropsychiatric Disorders.
Decades of research have demonstrated that rapid alterations in protein abundance are required for synaptic plasticity, a cellular correlate for learning and memory. Control of protein abundance, known as proteostasis, is achieved across a complex neuronal morphology that includes a tortuous axon as well as an extensive dendritic arbor supporting thousands of individual synaptic compartments. To regulate the spatiotemporal synthesis of proteins, neurons must efficiently coordinate the transport and metabolism of mRNAs. Among multiple levels of regulation, transacting RNA binding proteins (RBPs) control proteostasis by binding to mRNAs and mediating their transport and translation in response to synaptic activity. In addition to synthesis, protein degradation must be carefully balanced for optimal proteostasis, as deviations resulting in excess or insufficient abundance of key synaptic factors produce pathologies. As such, mutations in components of the proteasomal or translational machinery, including RBPs, have been linked to the pathogenesis of neurological disorders such as Fragile X Syndrome (FXS), Fragile X Tremor Ataxia Syndrome (FXTAS), and Autism Spectrum Disorders (ASD). In this review, we summarize recent scientific findings, highlight ongoing questions, and link basic molecular mechanisms to the pathogenesis of common neuropsychiatric disorders.


SU-E-T-451: Optimization of Normalized Prescription Isodose Selection for Stereotactic Radiation Therapy: Conventional Vs. Robotic Linac.
To determine the optimal prescription isodose line that minimizes normal tissue irradiation for stereotactic radiation therapy comparing conventional linear accelerator and robotic delivery. A computer based digital torso phantom which has the capability to simulate respiratory and cardiac motion were used in this study. Spherical targets were constructed in lung and liver, with diameter of 20mm, 30mm, and 40mm. Two concentric 5mm shells, from the target surface extending 5mm radially and from 5mm to 10mm, were identified/contoured. Non-coplanar, non- opposing 3D conformal beams were designed for linac planning. Variable prescription isodose lines were achieved by varying the block margin. 4D dose calculation was used for moving target and surrounding tissue. After linac planning, the CT images and contours were transferred for Cyberknife® planning. Variable prescription isodose lines were achieved by inverse planning technique. Doses of 60Gy in 3 fractions were prescribed to cover exactly 95% of target tumor with each technology. gEUD (generalized effective uniform dose) with different formulations for parallel and serial tissues was used for comparison between different plans. For linac plans, the optimal prescription isodose line yielding maximum normal tissue sparing occurs between 50% and 70% for the lung tumor and 60% and 90% for liver tumor. The gEUD difference between plans with optimum and arbitrarily chosen prescription isodose line may be up to 20% of prescription dose. For Cyberknife plans, the optimal prescription isodose line is approximately 50% for tissues displaying either parallel or serial behavior. These results are similar for different tumor sizes. Both conventional linac and Cyberknife® delivery can provide conformal tumor coverage with normal tissue sparing. By carefully choosing the optimal prescription isodose line, the gEUD of the surrounding normal tissue can be reduced by up to 20% of prescription dose.


Stepwise Regression and Latent Profile Analyses of Locomotor Outcomes Poststroke.
Previous data suggest patient demographics and clinical presentation are primary predictors of motor recovery poststroke, with minimal contributions of physical interventions. Other studies indicate consistent associations between the amount and intensity of stepping practice with locomotor outcomes. The goal of this study was to determine the relative contributions of these combined variables to locomotor outcomes poststroke across a range of patient demographics and baseline function. Data were pooled from 3 separate trials evaluating the efficacy of high-intensity training, low-intensity training, and conventional interventions. Demographics, clinical characteristics, and training activities from 144 participants >1-month poststroke were included in stepwise regression analyses to determine their relative contributions to locomotor outcomes. Subsequent latent profile analyses evaluated differences in classes of participants based on their responses to interventions. Stepwise regressions indicate primary contributions of stepping activity on locomotor outcomes, with additional influences of age, duration poststroke, and baseline function. Latent profile analyses revealed 2 main classes of outcomes, with the largest gains in those who received high-intensity training and achieved the greatest amounts of stepping practice. Regression and latent profile analyses of only high-intensity training participants indicated age, baseline function, and training activities were primary determinants of locomotor gains. Participants with the smallest gains were older (≈60 years), presented with slower gait speeds (<0.40 m/s), and performed 600 to 1000 less steps/session. Regression and cluster analyses reveal primary contributions of training interventions on mobility outcomes in patients >1-month poststroke. Age, duration poststroke, and baseline impairments were secondary predictors. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02507466 and NCT01789853.


Effects of a Multimodal Program Including Simulation on Job Strain Among Nurses Working in Intensive Care Units: A Randomized Clinical Trial.
Nurses working in an intensive care unit (ICU) are exposed to occupational stressors that can increase the risk of stress reactions, long-term absenteeism, and turnover. To evaluate the effects of a program including simulation in reducing work-related stress and work-related outcomes among ICU nurses. Multicenter randomized clinical trial performed at 8 adult ICUs in France from February 8, 2016, through April 29, 2017. A total of 198 ICU nurses were included and followed up for 1 year until April 30, 2018. The ICU nurses who had at least 6 months of ICU experience were randomized to the intervention group (n = 101) or to the control group (n = 97). The nurses randomized to the intervention group received a 5-day course involving a nursing theory recap and situational role-play using simulated scenarios (based on technical dexterity, clinical approach, decision making, aptitude to teamwork, and task prioritization), which were followed by debriefing sessions on attitude and discussion of practices. The primary outcome was the prevalence of job strain assessed by combining a psychological demand score greater than 21 (score range, 9 [best] to 36 [worst]) with a decision latitude score less than 72 (score range, 24 [worst] to 96 [best]) using the Job Content Questionnaire and evaluated at 6 months. There were 7 secondary outcomes including absenteeism and turnover. Among 198 ICU nurses who were randomized (95 aged ≤30 years [48%] and 115 women [58%]), 182 (92%) completed the trial for the primary outcome. The trial was stopped for efficacy at the scheduled interim analysis after enrollment of 198 participants. The prevalence of job strain at 6 months was lower in the intervention group than in the control group (13% vs 67%, respectively; between-group difference, 54% [95% CI, 40%-64%]; P < .001). Absenteeism during the 6-month follow-up period was 1% in the intervention group compared with 8% in the control group (between-group difference, 7% [95% CI, 1%-15%]; P = .03). Four nurses (4%) from the intervention group left the ICU during the 6-month follow-up period compared with 12 nurses (12%) from the control group (between-group difference, 8% [95% CI, 0%-17%]; P = .04). Among ICU nurses, an intervention that included education, role-play, and debriefing resulted in a lower prevalence of job strain at 6 months compared with nurses who did not undergo this program. Further research is needed to understand which components of the program may have contributed to this result and to evaluate whether this program is cost-effective. ClinicalTrials.gov Identifier: NCT02672072.


Use of magnetic resonance imaging for morphometric analysis of the caudal cranial fossa in Cavalier King Charles Spaniels.
To perform morphometric analysis of the caudal cranial fossa in Cavalier King Charles Spaniels (CKCSs), to assess the relationship between caudal fossa dimensions and the frequency of magnetic resonance imaging (MRI) features of occipital abnormalities in CKCSs (with and without syringomyelia), and to compare caudal cranial fossa measurements in CKCSs with measurements of 2 groups of mesaticephalic dogs. 70 CKCSs and 80 mesaticephalic (control) dogs. Dogs were placed into 4 groups as follows: Labrador Retrievers (n = 40), spaniel-type dogs (40; English Springer Spaniels and Cocker Spaniels), CKCSs with syringomyelia (55), and CKCSs without syringomyelia (15). Multiple morphometric measurements (linear, angular, and area) were obtained from cranial midsagittalT2-weighted magnetic resonance images including the brain and cervical portion of the spinal cord. Several specific MRI findings were also recorded for CKCSs that appeared to affect the occipital bone and cervicomedullary junction. No significant difference was identified among breeds in control groups and between sexes in any of the groups for all morphometric measurements. Significant differences were identified in CKCSs, compared with mesaticephalic dogs, in the area of the caudal cranial fossa and for several linear measurements that reflected the length of the ventral aspect of the occipital bone. These differences were greater in CKCSs with syringomyelia. All CKCSs had abnormalities in occipital bone shape. CKCSs had a shallower caudal cranial fossa and abnormalities of the occipital bone, compared with those of mesaticephalic dogs. These changes were more severe in CKCSs with syringomyelia.


Properties of a new protein film from bitter vetch (Vicia ervilia) and effect of CaCl₂ on its hydrophobicity.
This work was aimed to investigate the potential preparation of an edible film from bitter vetch seed proteins. The film was cast from bitter vetch protein concentrate (BPC) and glycerol. CaCl₂ at the ratio of 0.1-1% (w/w) of the BPC was tested to improve film properties, specially its hydrophobicity. Some physicochemical properties of the films obtained in the absence and presence of CaCl₂ were evaluated. The results indicated that moisture content, total soluble matter, water vapour permeability and contact angle of the films prepared in the presence of CaCl₂ were significantly modified in comparison with the control values, while their mechanical properties did not significantly change. The surface morphology of the films was also considerably affected by the presence of CaCl₂. Therefore, CaCl₂ could improve BPC-films barrier properties especially their hydrophobicity, even though calcium concentration seems to be a crucial factor.


The non-occupational environment and the lung: opportunities for intervention.
Many environmental factors, both indoors and outdoors, can cause or worsen respiratory disease. Although in many cases individuals have little influence over environmental exposures (e.g., weather conditions), there are many (such as environmental tobacco smoke (ETS) and outdoor air pollution) where interventions can improve health. While for environmental exposures such as air pollution, remediation largely devolves to the government, for exposures such as ETS advice to individuals in these settings will confer benefit. Climate change has begun to feature more and more in the context of health but how this may affect pulmonary disease remains debatable. It is possible that heat associated changes in allergen exposures may be more than counterbalanced by potential reductions in cold related exacerbations of diseases such as COPD. An improved assessment of environmental exposures is key in how we approach the effects of the environment on lung disease which would allow better understanding of gene-environment interactions and how remediation might influence population health for the better.


Urinary incontinence and psychological distress in community-dwelling older adults.
To examine the relationship between urinary incontinence (UI) and psychological distress in older adults. We hypothesized that persons with UI associated with condition-specific functional loss would be most likely to report psychological distress. A population-based longitudinal survey. Continuing participants in a study of community-dwelling adults who were initially living in East Baltimore in 1981. Persons aged 50 and older (n=781) at follow-up interviews conducted between 1993 and 1996 for whom complete data were available. Participants were classified as incontinent if they reported any uncontrolled urine loss within the 12 months preceding the 13-year follow-up interview. Condition-specific functional loss secondary to UI was further assessed based on a series of questions relating directly to participants' inability to engage in certain activities due to their UI. Psychological distress was assessed using the General Health Questionnaire (GHQ) at interviews in 1981 and at the 13-year follow-up. Persons with UI were more likely to experience psychological distress as measured by the GHQ than were persons without UI (unadjusted odds ratio (OR)=1.74, 95% confidence interval (CI)=1.13-2.68). Persons with condition-specific functional loss secondary to UI were substantially more likely to have psychological distress as measured by the GHQ than were persons without UI (unadjusted OR=4.02, 95% CI=1.86-8.70). In multivariate models that controlled for potentially influential characteristics such as age, gender, ethnicity, and chronic medical conditions the association between condition-specific functional loss secondary to UI and psychological distress remained statistically significant. Among people with UI, persons with persistently elevated GHQ scores were much more likely to report condition-specific functional impairment from UI (adjusted OR=6.55, 95% CI=1.94-22.12). Individuals with UI, especially when incontinence was associated with condition-specific functional loss, were more likely to have psychological distress than were other older adults. Our findings support a general conceptual model that condition-specific functional impairment mediates the relationship between a chronic medical condition and psychological distress.


Handwriting Legibility and Its Relationship to Spelling Ability and Age: Evidence From Monolingual and Bilingual Children.
Studies of the relationship between spelling and handwriting concur that spelling skills influence the dynamic processes of handwriting. However, it remains unclear whether variations in spelling ability are related to variations in the legibility of handwriting, how important spelling skills are relative to the amount of handwriting experience afforded by an individual's age and number of years of schooling, or to what extent this relationship may be task- and orthography-specific. We investigated these questions in a study comparing spelling and handwriting legibility in a group of N = 127 Welsh-English bilingual children matched in age and number of years of schooling to a group of N = 127 English-monolingual children, as well as to a group of N = 127 younger, English monolingual children matched to the bilingual group in spelling ability. All groups completed the Spelling and Handwriting Legibility Test (SaHLT) and a broader battery of literacy measures. The bilingual children were found to have poorer handwriting legibility than same age peers, and in some cases, than their younger, spelling-ability peers, suggesting that spelling ability, more so than amount of handwriting experience and years of schooling impacts handwriting legibility. This was corroborated in a series of multi-group path models, where all children's handwriting was predicted by spelling ability more strongly than by age, and, the effect of spelling generalized across two different spelling tasks in all groups. Finally, bilingual children seemed to draw on general (Welsh) as well as on orthography-specific (English) knowledge when handwriting in English.