Glenohumeral relationships: subchondral mineralization patterns, thickness of cartilage, and radii of curvature.
Subchondral mineralization represents the loading history of a joint and can be measured in vivo using computed tomography osteoabsorptiometry. Different mineralization patterns in the glenohumeral joint have been explained by the principle of physiologic incongruence. We sought to support this explanation by measurement of mineralization, radii, and cartilage thickness in 18 fresh shoulder specimens. We found three mineralization patterns: bicentric, monocentric anterior, and monocentric central. Mean radii of the glenoids were 27.4 mm for bicentric glenoids, 27.3 mm for monocentric anterior, and 24.8 mm for monocentric central glenoids. Cartilage thickness measurement revealed the highest values in anterior parts; the thinnest cartilage was found centrally. Our findings support the principle of a physiologic incongruence in the glenohumeral joint. Bicentric mineralization patterns exist in joints consisting of more flat glenoids compared to the corresponding humeral head. Monocentric distribution with a central maximum was found in specimens with glenoids being more curved, indicating higher degrees of congruence, which might represent an early stage of degenerative disease. The obtained information might also be important for implant fixation in resurfacing procedures or to achieve the best possible fit of an osteochondral allograft in the repair of cartilage defects.


Wildfire risk transmission in the Colorado Front Range, USA.
Wildfires are a global phenomenon that in some circumstances can result in human casualties, economic loss, and ecosystem service degradation. In this article we spatially identify wildfire risk transmission pathways and locate the areas of highest exposure of human populations to wildland fires under severe, but not uncommon, weather events. We quantify varying levels of exposure in terms of population potentially affected and tie the exposure back to the spatial source of the risk for the Front Range of Colorado, USA. We use probabilistic fire simulation modeling to address where fire ignitions are most likely to cause the highest impact to human communities, and to explore the role that various landowners play in that transmission of risk. Our results indicated that, given an ignition and the right fire weather conditions, large areas along the Front Range in Colorado could be exposed to wildfires with high potential to impact human populations, and that overall private ignitions have the potential to impact more people than federal ignitions. These results can be used to identify high-priority areas for wildfire risk mitigation using various mitigation tools.


Primary cardioprotection with dexrazoxane in patients with childhood cancer who are expected to receive anthracyclines: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.
Survivors of childhood cancer are at risk of anthracycline-induced cardiotoxicity, which might be prevented by dexrazoxane. However, concerns exist about the safety of dexrazoxane, and little guidance is available on its use in children. To facilitate global consensus, a working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the existing literature and used evidence-based methodology to develop a guideline for dexrazoxane administration in children with cancer who are expected to receive anthracyclines. Recommendations were made in consideration of evidence supporting the balance of potential benefits and harms, and clinical judgement by the expert panel. Given the dose-dependent risk of anthracycline-induced cardiotoxicity, we concluded that the benefits of dexrazoxane probably outweigh the risk of subsequent neoplasms when the cumulative doxorubicin or equivalent dose is at least 250 mg/m2 (moderate recommendation). No recommendation could be formulated for cumulative doxorubicin or equivalent doses of lower than 250 mg/m2, due to insufficient evidence to determine whether the risk of cardiotoxicity outweighs the possible risk of subsequent neoplasms. Further research is encouraged to determine the long-term efficacy and safety of dexrazoxane in children with cancer.


Assigning resources to health care use for health services research: options and consequences.
Our goals are 3-fold: (1) to review the leading options for assigning resource coefficients to health services utilization; (2) to discuss the relative advantages of each option; and (3) to provide examples where the research question had marked implications for the choice of which resource measure to employ. Three approaches have been used to establish relative resource weights in health services research: (a) direct estimation of production costs through microcosting or step down allocation methods; (b) macrocosting/regression analysis; and (c) standardized resource assignment. We describe each of these methods and provide examples of how the study question drove the choice of resource-use measure. All empirical resource-intensity weighting systems contain distortions that limit their universal application. Hence, users must select the weighting system that matches the needs of their specific analysis. All systems require significant data resources and data processing. However, inattention to the distortions contained in a complex resource weighting system may undermine the validity and generalizability of an economic evaluation. Direct estimation of production costs are useful for empirical analyses, but they contain distortions that undermine optimal resource allocation decisions. Researchers must ensure that the data being used meets both the study design and the question being addressed. They also should ensure that the choice of resource measure is the best fit for the analysis. IMPLICATIONS FOR RESEARCH AND POLICY: Researchers should consider which of the available measures is the most appropriate for the question being addressed rather than take "cost " or utilization as a variable over which they have no control.


Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide attenuate the cigarette smoke extract-induced apoptotic death of rat alveolar L2 cells.
Chronic obstructive pulmonary disease is a major clinical disorder usually associated with cigarette smoking. A central feature of chronic obstructive pulmonary disease is inflammation coexisting with an abnormal protease/antiprotease balance, leading to apoptosis and elastolysis. In an in vitro study of rat lung alveolar L2 cells, cigarette smoke extract (CSE) induced apoptotic cell death. Exposure of L2 cells to CSE at a concentration of 0.25% resulted in a 50% increase of caspase-3 and matrix metalloproteinase (MMP) activities. Specific inhibitors for caspases and MMPs attenuated the cytotoxicity of CSE. RT-PCR amplification identified VPAC2 receptors in L2 cells. A radioligand-binding assay with (125)I-labeled vasoactive intestinal peptide (VIP) found high affinity and saturable (125)I-labeled VIP-binding sites in L2 cells. VIP and pituitary adenylate cyclase-activating polypeptide (PACAP27) were approximately equipotent for both VIP receptor binding and stimulation of cAMP production in L2 cells. Both neuropeptides, at concentrations higher than 10(-13) m, produced a concentration-dependent inhibition of CSE-induced cell death in L2 cells. VIP, at 10(-7) m, reduced CSE-stimulated MMP activity and caspase-3 activation. The present study has shown that VIP and PACAP27 significantly attenuate the cytotoxicity of CSE through the activation of VPAC2 receptor, and the protective effect of VIP may partly be the result of a reduction in the CSE-induced stimulation of MMPs and caspases.


Pharmacological and toxicological properties of ryodipine.
2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxy-p hen yl)-1,4-dihydropyridine (ryodipine, PP-1466) causes lasting decrease in systolic and diastolic arterial pressure at intravenous and oral administration to anesthetized animals. In conscious rats with DOCA-salt (des-oxycortone) and spontaneous hypertension, as well as in rats with hypertension provoked by method of cellophane perinephritis, PP-1466 (1 and 10 mg/kg, orally) decreases systolic pressure considerably. Therapeutic doses of PP-1466 do not essentially affect rhythm and frequency of cardiac contractions. High doses of the drug increase the heart rate. PP-1466 increases coronary blood flow. PP-1466 antagonizes considerably the pressor effect of angiotensin. In this respect PP-1466 is superior to SKF-24260 (2,6-dimethyl-3,5-diethoxycarbonyl-4-(o-difluoromethylphenyl)-1, 4-dihydropyridine). PP-1466 reduces hypotensive reaction and tachycardia induced by isoprenaline administration, inhibits decrease in arterial pressure caused by electric stimulation of the vagus nerve and administration of acetylcholine. Hypotension caused by PP-1466 and its negative inotropic effect can be antagonized with calcium chloride. In mice and rats PP-1466 at doses exceeding 10 mg/kg exerts a certain dose dependent depressant effect on the CNS. More protracted depressant effect on the CNS is exerted by nifedipine which was studied parallelly. In rabbits oral PP-1466 decreases in EEG basic rhythm amplitude both in cortical and subcortical structures. High doses of the drug lead to dysrhythmia in bioelectric activity. Acute, subacute and chronic toxicity studies in mice, rats and dogs show that PP-1466 possesses low acute toxicity and is well tolerated at protracted repeated administration of therapeutic and several times higher doses.


Unraveling somatotopic organization in the human brain using machine learning and adaptive supervoxel-based parcellations.
In addition to the well-established somatotopy in the pre- and post-central gyrus, there is now strong evidence that somatotopic organization is evident across other regions in the sensorimotor network. This raises several experimental questions: To what extent is activity in the sensorimotor network effector-dependent and effector-independent? How important is the sensorimotor cortex when predicting the motor effector? Is there redundancy in the distributed somatotopically organized network such that removing one region has little impact on classification accuracy? To answer these questions, we developed a novel experimental approach. fMRI data were collected while human subjects performed a precisely controlled force generation task separately with their hand, foot, and mouth. We used a simple linear iterative clustering (SLIC) algorithm to segment whole-brain beta coefficient maps to build an adaptive brain parcellation and then classified effectors using extreme gradient boosting (XGBoost) based on parcellations at various spatial resolutions. This allowed us to understand how data-driven adaptive brain parcellation granularity altered classification accuracy. Results revealed effector-dependent activity in regions of the post-central gyrus, precentral gyrus, and paracentral lobule. SMA, regions of the inferior and superior parietal lobule, and cerebellum each contained effector-dependent and effector-independent representations. Machine learning analyses showed that increasing the spatial resolution of the data-driven model increased classification accuracy, which reached 94% with 1755 supervoxels. Our SLIC-based supervoxel parcellation outperformed classification analyses using established brain templates and random simulations. Occlusion experiments further demonstrated redundancy across the sensorimotor network when classifying effectors. Our observations extend our understanding of effector-dependent and effector-independent organization within the human brain and provide new insight into the functional neuroanatomy required to predict the motor effector used in a motor control task.


A preliminary study on the use and effect of hand antiseptics in veterinary practice.
To assess use and effect of hand antiseptics in veterinary clinical practice. Veterinary practice nurses were questioned concerning their use of hand antiseptics, in particular waterless hand rubs. Subsequent clinical trials assessed the effect of single applications of alcohol-based and quaternary ammonium compound-based hand rubs at reducing bacterial counts on the hands of theatre nurses in a neutering clinic. The majority of responding practices used waterless hand rubs (alcohol-based, 67.5% and quaternary ammonium compound-based, 9.5%) as their primary hand hygiene agent and believed them to be effective. 23% of practices favoured an antiseptic hand-wash. In clinical trials, alcohol-based rubs were potentially more effective at reducing bacterial counts than quaternary ammonium compound-based rubs especially in the period immediately after application. However, over 3 hours there was no significant change between these and a control group. There were more adverse skin effects in the group using alcohol-based than in the quaternary ammonium compound-based and control groups. The bacterial counts after application were unaffected by variables such as the number of animals contacted. The studies provide useful baseline data for evaluation of efficacy of more frequent applications of the most common antiseptic hand rubs used in veterinary practice.


Allelic exclusion of the TCR alpha-chain is an active process requiring TCR-mediated signaling and c-Cbl.
Phenotypic allelic exclusion at the TCRalpha locus is developmentally regulated in thymocytes. Many immature thymocytes express two cell surface alpha-chain species. Following positive selection, the vast majority of mature thymocytes and peripheral T cells display a single cell surface alpha-chain. A posttranslational mechanism occurring at the same time as positive selection and TCR up-regulation leads to this phenotypic allelic exclusion. Different models have been proposed to explain the posttranslational regulation of the alpha-chain allelic exclusion. In this study, we report that allelic exclusion is not regulated by competition between distinct alpha-chains for a single beta-chain, as proposed by the dueling alpha-chain model, nor by limiting CD3 zeta-chain in mature TCR(high) thymocytes. Our data instead favor the selective retention model where the positive selection signal through the TCR leads to phenotypic allelic exclusion by specifically maintaining cell surface expression of the selected alpha-chain while the nonselected alpha-chain is internalized. The use of inhibitors specific for Lck and/or other Src kinases indicates a role for these protein tyrosine kinases in the signaling events leading to the down-regulation of the nonselectable alpha-chain. Loss of the ubiquitin ligase/TCR signaling adapter molecule c-Cbl, which is important in TCR down-modulation and is a negative regulator of T cell signaling, leads to increased dual alpha-chain expression on the cell surface of double-positive thymocytes. Thus, not only is there an important role for TCR signaling in causing alpha-chain allelic exclusion, but differential ubiquitination by c-Cbl may be an important factor in causing only the nonselected alpha-chain to be down-modulated.


Myocardial Energetics in Heart Failure With Preserved Ejection Fraction.
The role of coronary microvascular disease and its impact on functional and energetic reserve in heart failure with preserved ejection fraction (HFpEF) remains unclear. We hypothesized that in response to submaximal pharmacologic stress (dobutamine), patients with HFpEF have impairment in left ventricular (LV) myocardial mechanical (external work [EW]), energetic (myocardial O2 consumption [MVO2]), and myocardial blood flow (MBF) reserve. We further assessed whether coupling of MBF to EW is impaired in HFpEF and associated with compensatory increases or pathological decreases in myocardial O2 extraction. Lastly, we assessed whether coupling of MVO2 to EW (mechanical efficiency) was impaired in HFpEF. In prospectively enrolled patients with HFpEF (n=19) and age/sex-matched healthy controls (n=19), we performed 11C-acetate positron emission tomography assessing MVO2 and MBF at rest and during dobutamine infusion. EW was calculated as stroke volume (echo)×end-systolic pressure×heart rate. At rest, compared with controls, patients with HFpEF had higher LV EW, MVO2, and MBF. With dobutamine, LV EW, MVO2, and MBF increased in both HFpEF and controls; however, the magnitude of increases was significantly smaller in HFpEF. In both groups, MBF increased in relation to EW, but in HFpEF, the slope of the relationship was significantly smaller than in controls. Myocardial O2 extraction was increased in HFpEF. Mechanical efficiency was similar in HFpEF and controls. In a post hoc analysis, HFpEF patients with LV hypertrophy (n=10) had significant reductions in LV mechanical efficiency relative to controls. In HFpEF during submaximal dobutamine stress, there is myocardial mechanical-, energetic- and flow-reserve dysfunction with impaired coupling of blood flow to demand and slight increases in myocardial O2 extraction. These findings provide evidence that coronary microvascular dysfunction is present in HFpEF, limits O2 supply relative to demand, and is associated with reserve dysfunction.


Dental care for the underserved children of Monterey County: meeting the challenge.
With its expansive area, and the special needs of agricultural workers, Monterey County held significant challenges for setting up a children's health clinic. Part of the solution to addressing the county's unmet dental needs was the establishment of the Children's Miracle Network dental center in 1995. But working in the fields leaves little time for travel to appointments, so the dental center expanded to a mobile unit that can go where the need is. Understanding the special needs of one's community is crucial to establishing programs that can successfully address the state's needs for children's dental care.


Manubriosternal joint subluxation in rheumatoid arthritis.
Manubriosternal joint involvement in rheumatoid arthritis is not rare and may be evidenced by erosion, reactive sclerosis and ankylosis. Frequent reports of such involvements appear in the radiological literature but only 3 cases where this had been associated with clinically evident subluxation of the joint have been reported previously. It is, nonetheless, our observation that clinical deformity of this joint is common and careful review at our clinic has revealed the 10 cases reported here. Chronic or recurrent chest infections have been incriminated in the production of this deformity. However, the evidence seen in our series suggests rather, that this deformity is closely associated with severe cervicodorsal spinal erosion and deformity and that its presence should alert clinicians to potential problems of cervical cord compression.


Submodular Attribute Selection for Visual Recognition.
In real-world visual recognition problems, low-level features cannot adequately characterize the semantic content in images, or the spatio-temporal structure in videos. In this work, we encode objects or actions based on attributes that describe them as high-level concepts. We consider two types of attributes. One type of attributes is generated by humans, while the second type is data-driven attributes extracted from data using dictionary learning methods. Attribute-based representation may exhibit variations due to noisy and redundant attributes. We propose a discriminative and compact attribute-based representation by selecting a subset of discriminative attributes from a large attribute set. Three attribute selection criteria are proposed and formulated as a submodular optimization problem. A greedy optimization algorithm is presented and its solution is guaranteed to be at least (1-1/e)-approximation to the optimum. Experimental results on four public datasets demonstrate that the proposed attribute-based representation significantly boosts the performance of visual recognition and outperforms most recently proposed recognition approaches.


Genetic variance of sexually selected traits in waxmoths: maintenance by genotype x environment interaction.
When traits experience directional selection, such as that imposed by sexual selection, their genetic variance is expected to diminish. Nonetheless, theory and findings from sexual selection predict and demonstrate that male traits favored by female choice retain substantial amounts of additive genetic variance. We explored this dilemma through an ecological genetic approach and focused on the potential contributions of genotype x environment interaction (GEI) to maintenance of additive genetic variance for male signal characters in the lesser waxmoth, Achroia grisella (Lepidoptera: Pyralidae). We artificially selected genetic variants for two male signal characters, signal rate (SR) and peak amplitude (PA), that influence female attraction and then examined the phenotypic plasticity of these variants (high- and low-SR and high- and low-PA lines) under a range of environmental conditions expected in natural populations. Our split-family breeding experiments indicated that two signal characters, SR and PA, and several developmental characters in both high- and low-SR and high- and low-PA lines displayed considerable phenotypic plasticity among the environments tested. Moreover, strong GEIs leading to crossover between high- and low-SR lines were found for SR and developmental period. Therefore, neither high- nor low-SR genetic variants would achieve maximum attractiveness and fitness in every environment, and those variants producing unattractive signals with low SRs under normal conditions may remain in populations provided that gene flow across environments or generation overlap are sufficiently high. We speculate that the phenotypic plasticity for SR and developmental period is adaptive in A. grisella populations experiencing a range of temperature and density conditions. Females mating with attractive (high-SR) males may be assured of obtaining good genes because these males sire offspring that develop more rapidly and a crossover for developmental period may parallel that for SR. Such parallel crossovers may be expected wherever good-genes sexual selection mechanisms operate.


Myosin VI and optineurin are required for polarized EGFR delivery and directed migration.
The polarized trafficking of membrane proteins into the leading edge of the cell is an integral requirement for cell migration. Myosin VI and its interacting protein optineurin have previously been shown to operate in anterograde trafficking pathways, especially for the polarized delivery of cargo to the basolateral domain in epithelial cells. Here we show that in migratory cells ablation of myosin VI or optineurin inhibits the polarized delivery of the epidermal growth factor receptor (EGFR) into the leading edge and leads to profound defects in lamellipodia formation. Depletion of either myosin VI or optineurin, however, does not impair the overall ability of cells to migrate in a random migration assay, but it dramatically reduces directed migration towards a growth factor stimulus. In summary, we identified a specific role for myosin VI and optineurin in directionally persistent cell migration, which involves the polarized delivery of vesicles containing EGFR into the leading edge of the cell.


GnRHa flare and IVF pregnancy rates.
GnRH agonist administered early in the menstrual cycle (flare) causes an endogenous discharge of FSH and LH. Flare has been used in conjunction with gonadotropin ovarian stimulation for IVF 'poor responders'. There is an ongoing controversy regarding whether flare protocols improve pregnancy rates in 'poor responders'. The current study was designed to compare a GnRHa flare protocol with long suppression GnRHa IVF in 'poor responders'. Seventy-three newly diagnosed poor responders who failed long GnRHa suppression IVF attempts were compared retrospectively with 128 age-matched IVF patients previously known poor ovarian responders treated with a long GnRHa suppression protocol. 'Poor responders' consisted of patients with peak E(2) less than 1000 pg/ml and/or less than five mature follicles with diameter >15 mm on the day of hCG administration. Student's t-test was used to analyze the data and the chi-squared test was used to compare fertilization and pregnancy rates. The flare protocol produced higher peak E(2) levels (1647+/-747 vs. 720+/-258 mIU/ml, P<0.05) and a larger number of mature follicles (5.8+/-2.2 vs. 4.0+/-1.0 P<0.05) in the study vs. the control group. A 30% pregnancy rate was achieved during this second IVF attempt using GnRHa flare protocol in the study group vs. 37 in the control group (P>0.05, NS). A comparison between the flare protocol group and the age-matched control group of poor ovarian responders subject to down regulation protocol, revealed higher peak E(2) levels and more mature follicles, respectively. However, both groups yielded comparable pregnancy rates. The use of high dose gonadotropin treatment in our study groups seems to be the only explanation for their subsequent successful outcome. We concluded that GnRH agonist flare protocol does not result in better IVF outcome compared with long GnRH agonist suppression protocol in IVF poor responders.


A Contemporary Treatment Approach to Both Diabetes and Depression by Cordyceps sinensis, Rich in Vanadium.
Diabetes mellitus is accompanied by hormonal and neurochemical changes that can be associated with anxiety and depression. Both diabetes and depression negatively interact, in that depression leads to poor metabolic control and hyperglycemia exacerbates depression. We hypothesize one novel vanadium complex of vanadium-enriched Cordyceps sinensis (VECS), which is beneficial in preventing depression in diabetes, and influences the long-term course of glycemic control. Vanadium compounds have the ability to imitate the action of insulin, and this mimicry may have further favorable effects on the level of treatment satisfaction and mood. C. sinensis has an antidepressant-like activity, and attenuates the diabetes-induced increase in blood glucose concentrations. We suggest that the VECS may be a potential strategy for contemporary treatment of depression and diabetes through the co-effect of C. sinensis and vanadium. The validity of the hypothesis can most simply be tested by examining blood glucose levels, and swimming and climbing behavior in streptozotocin-induced hyperglycemic rats.


Synthesis of benzimidazole-fused 1,4-benzoxazepines and benzosultams spiro-connected to a 2-oxindole core via a tandem epoxide-opening/SNAr approach.
While hundreds of literature reports describe the preparation of spirooxindole-based five- and six-membered heterocycles, the construction of seven-membered heterocyclic rings spiro-connected to a 2-oxindole core has so far been less developed. Herein, we disclose a base-mediated (4 + 3) annulation of spiro-epoxyoxindoles and 2-(2-fluoroaryl)-1H-benzoimidazoles or 2-fluoro-N-arylbenzenesulfonamides toward the synthesis of two new classes of spirooxindole-based polycyclic systems. Mechanistically, this conceptually simple and high atom-economical reaction proceeds via an SN2-like intermolecular epoxide ring-opening, accompanied by a concomitant intramolecular SNAr reaction. From a synthetic aspect, the notable features of the process are its full regioselectivity, operational simplicity using readily available substrates under transition-metal-free conditions, high yields, and broad substrate scope.


SIRT2 transgenic over-expression does not impact lifespan in mice.
The NAD+ -dependent deacylase family of sirtuin enzymes have been implicated in biological ageing, late-life health and overall lifespan, though of these members, a role for sirtuin-2 (SIRT2) is less clear. Transgenic overexpression of SIRT2 in the BubR1 hypomorph model of progeria can rescue many aspects of health and increase overall lifespan, due to a specific interaction between SIRT2 and BubR1 that improves the stability of this protein. It is less clear whether SIRT2 is relevant to biological ageing outside of a model where BubR1 is under-expressed. Here, we sought to test whether SIRT2 over-expression would impact the overall health and lifespan of mice on a nonprogeroid, wild-type background. While we previously found that SIRT2 transgenic overexpression prolonged female fertility, here, we did not observe any additional impact on health or lifespan, which was measured in both male and female mice on standard chow diets, and in males challenged with a high-fat diet. At the biochemical level, NMR studies revealed an increase in total levels of a number of metabolites in the brain of SIRT2-Tg animals, pointing to a potential impact in cell composition; however, this did not translate into functional differences. Overall, we conclude that strategies to enhance SIRT2 protein levels may not lead to increased longevity.


What is medicinal chemistry? - Demystifying a rapidly evolving discipline!
Medicinal chemistry is a scientific discipline that has progressed rapidly over the last few decades. Facilitated by the technological advancement, the early understanding of medicinal chemistry as "synthesizing bioactive molecules" has become the connecting bridge of a variety of related scientific disciplines. This opinion article will guide you through a brief evolution of this discipline and discuss what medicinal chemistry has evolved to be in this era.


Bioengineered 3D Glial Cell Culture Systems and Applications for Neurodegeneration and Neuroinflammation.
Neurodegeneration and neuroinflammation are key features in a range of chronic central nervous system (CNS) diseases such as Alzheimer's and Parkinson's disease, as well as acute conditions like stroke and traumatic brain injury, for which there remains significant unmet clinical need. It is now well recognized that current cell culture methodologies are limited in their ability to recapitulate the cellular environment that is present in vivo, and there is a growing body of evidence to show that three-dimensional (3D) culture systems represent a more physiologically accurate model than traditional two-dimensional (2D) cultures. Given the complexity of the environment from which cells originate, and their various cell-cell and cell-matrix interactions, it is important to develop models that can be controlled and reproducible for drug discovery. 3D cell models have now been developed for almost all CNS cell types, including neurons, astrocytes, microglia, and oligodendrocyte cells. This review will highlight a number of current and emerging techniques for the culture of astrocytes and microglia, glial cell types with a critical role in neurodegenerative and neuroinflammatory conditions. We describe recent advances in glial cell culture using electrospun polymers and hydrogel macromolecules, and highlight how these novel culture environments influence astrocyte and microglial phenotypes in vitro, as compared to traditional 2D systems. These models will be explored to illuminate current trends in the techniques used to create 3D environments for application in research and drug discovery focused on astrocytes and microglial cells.


Gene-coding assignments of rotavirus double-stranded RNA segments 10 and 11.
The gene-coding assignments for genome segments 10 and 11 of a simian virus and two human rotaviruses were determined. For those viruses having a "long" RNA gel pattern (electropherotype), segments 10 and 11 encoded proteins NS(3) and O(4), respectively. The human virus with a "short" electropherotype had the opposite assignments and also differed in (enzyme-linked immunosorbent assay) serotype from the human virus with a long electropherotype.


Nymph and adult biology of Dichelops melacanthus (Dallas) (Heteroptera: Pentatomidae) feeding on cultivated and non-cultivated host plants.
The biology of the pentatomid Dichelops melacanthus (Dallas) feeding on cultivated and non-cultivated plants was studied in the laboratory. Nymph mortality varied from approximately 60 on corn (seed mature) to 77% on wheat (ear immature); no nymphs survived on seedlings of corn or wheat. Nymph developmental time on soybean, corn or wheat (seed, pod or ear) varied from 25.5 to 32.8 days. Body weight at adult emergence was similar and greater on most foods than on wheat ear. Nymphs fed preferentially on soybean (pod immature). On non-cultivated hosts, nymphs showed high mortality (73%) on crotalaria (pod immature); on tropical spiderwort (stem) all nymphs died. Nymphs took longer time to develop on crotalaria and/or on spiderwort than on soybean. Body weight at adult emergence did not differ on crotalaria or soybean. Survivorship decreased with time on most foods, with approximately 50% of adults alive at day 30. On corn and wheat seedlings approximately 80% of adults were dead on day 20. Adult longevity ranged 31-43 days, except on corn and wheat seedlings < 15 days. Females % ovipositing peaked ( approximately 76%) on soybean (pod or seed immature), and was minimum ( approximately 9%) on wheat ear (immature); no females reproduced on seedlings of corn or wheat. Preoviposition period was shorter ( approximately 12 days) on soybean (immature pod or seed) and longer ( approximately 37 days) on wheat (ear immature). Fecundity was similar and higher on all foods than on wheat (ear immature). Body weigh gain occurred on all foods, but on corn and wheat seedlings. Adults fed preferably on soybean (pod immature and seed mature); wheat (seedling) was the least preferred food.


A Comparison Between Recombinant Listeria GAPDH Proteins and GAPDH Encoding mRNA Conjugated to Lipids as Cross-Reactive Vaccines for Listeria, Mycobacterium, and Streptococcus.
Cross-reactive vaccines recognize common molecular patterns in pathogens and are able to confer broad spectrum protection against different infections. Antigens common to pathogenic bacteria that induce broad immune responses, such as the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of the genera Listeria, Mycobacterium, or Streptococcus, whose sequences present more than 95% homology at the N-terminal GAPDH1-22 peptide, are putative candidates for universal vaccines. Here, we explore vaccine formulations based on dendritic cells (DC) loaded with two molecular forms of Listeria monocytogenes GAPDH (LM-GAPDH), such as mRNA carriers or recombinant proteins, and compare them with the same molecular forms of three other antigens used in experimental vaccines, listeriolysin O of Listeria monocytogeness, Ag85A of Mycobacterium marinum, and pneumolysin of Streptococcus pneumoniae. DC loaded with LM-GAPDH recombinant proteins proved to be the safest and most immunogenic vaccine vectors, followed by mRNA encoding LM-GAPDH conjugated to lipid carriers. In addition, macrophages lacked sufficient safety as vaccines for all LM-GAPDH molecular forms. The ability of DC loaded with LM-GAPDH recombinant proteins to induce non-specific DC activation explains their adjuvant potency and their capacity to trigger strong CD4+ and CD8+ T cell responses explains their high immunogenicity. Moreover, their capacity to confer protection in vaccinated mice against challenges with L. monocytogenes, M. marinum, or S. pneumoniae validated their efficiency as cross-reactive vaccines. Cross-protection appears to involve the induction of high percentages of GAPDH1-22 specific CD4+ and CD8+ T cells stained for intracellular IFN-γ, and significant levels of peptide-specific antibodies in vaccinated mice. We concluded that DC vaccines loaded with L. monocytogenes GAPDH recombinant proteins are cross-reactive vaccines that seem to be valuable tools in adult vaccination against Listeria, Mycobacterium, and Streptococcus taxonomic groups.


Gynecologic cancer in patients with subacute cerebellar degeneration predicted by anti-Purkinje cell antibodies and limited in metastatic volume.
Between 1982 and 1989, 19 patients with gynecologic carcinoma, paraneoplastic cerebellar degeneration, and seropositivity for anti-Purkinje cell cytoplasmic antibodies were identified at our institution. Seven of the patients had no clinical, computed tomographic, or magnetic resonance imaging evidence of cancer but had undergone laparotomy solely because anti-Purkinje cell antibodies were found in their serum; all had high-grade adenocarcinoma. Cerebellar symptoms preceded or coincided with the initial cancer diagnosis in 15 patients and preceded the diagnosis of recurrent cancer in 4 patients. The cancers were 14 ovarian, 2 fallopian tube, 2 surface papillary, and 1 poorly differentiated metastatic adenocarcinoma in a periaortic lymph node. Two remarkable surgical observations in patients with high-grade ovarian and tubal cancers were the conspicuous lack of peritoneal implants and the small metastatic volume. A comparison of the 8 patients who had primary stage III cancer with 24 matched control patients without paraneoplastic cerebellar degeneration revealed no difference in primary tumor volume but a significantly smaller volume of metastatic tumor in the seropositive group (P = 0.05). Anti-Purkinje cell antibodies were not detected in 111 neurologically normal patients with advanced ovarian cancer. The small metastatic volume in the face of high-grade and advanced stage malignancy in seropositive patients with paraneoplastic cerebellar degeneration suggests that an immune response to the tumor (presumably cross-reactive with cerebellar cells) may impair the metastatic process. Earlier diagnosis and treatment of cancer, based on prompt serologic testing, may offer an improved neurologic and oncologic prognosis.


Cultivation and characterization of cells derived from mouse skin papillomas induced by an initiation-promotion protocol.
Methods to culture cells from papillomas induced by an initiation-promotion protocol in SENCAR mice were developed, and the resultant cell lines have been characterized. Using Eagle's medium with 0.05 mM Ca2+ conditioned by dermal fibroblasts and supplemented with 1 ng/ml epidermal growth factor (EGF) in culture dishes coated with collagen and fibronectin, six cell lines (PA, PB, PC, PD, PE and PF) were established from separate pools of papillomas. When tested for tumorigenicity in nude mice by injection of a cell suspension or implantation of cells growing on a plastic liner, two of the lines (PC and PF) produced no tumors at any passage. In contrast, cells of the lines PA and PE produced highly differentiated squamous cell carcinomas from the earliest passage tested. The results with PB and PD were variable on tumorigenicity testing with some passages positive and others negative. When tested for responsiveness to Ca2+ (greater than 0.1 mM) as a differentiation stimulus, all lines responded. In the higher Ca2+ medium there was a 50-95% decrease in colony-forming efficiency, a slight decrease in [3H]thymidine incorporation (except for PA) and an increase in the number of cornified cells (except for early passage PF). Epidermal transglutaminase activity, a marker for terminal differentiation, was increased in the presence of medium with Ca2+ greater than 0.1 mM. However, unlike normal cells, only a fraction of the cells from each of the papilloma-derived cell lines terminally differentiated in response to Ca2+ while the remaining cells continued to proliferate, although at a slower rate. Responsiveness to phorbol ester tumor promoters was also examined in papilloma cell lines. 12-O-Tetradecanoylphorbol-13-acetate (TPA) treatment increased colony forming efficiency, DNA synthesis and colony size in all lines in medium with either 0.05 mM Ca2+ or 1.2 mM Ca2+. TPA treatment also increased ornithine decarboxylase activity in all lines, even at the higher Ca2+ concentration, although normal keratinocytes respond only when grown in medium with low Ca2+. TPA treatment caused only a slight increase in the number of cornified cells and no increase in epidermal transglutaminase activity in papilloma cells while it causes 10-fold or greater increases in these differentiation markers in normal keratinocytes. Thus papilloma cells appear to differ from normal keratinocytes in their ability to maintain a proliferating population under conditions favoring terminal differentiation, their consistent proliferative response to phorbol esters under these same conditions, and their reduced sensitivity to phorbol ester-induced terminal differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)


A cyanogen bromide fragment of S4 that specifically rebinds 16S RNA.
Escherichia coli ribosomal protein S4 was subjected to cyanogen bromide cleavage and was found to generate a complete cleavage product capable of rebinding 16S rRNA. This fragment, consisting of residues 1-103, was found to bind with an apparent association constant of 11 microM-1. This fragment was used in place of S4 in an in vitro reconstitution experiment. Although the particles formed had a protein composition not significantly different from reconstituted 30S ribosomal subunits, their sedimentation behavior was more like that of particles reconstituted without S4. These results indicate to us that, although residues 104-203 of S4 are involved in the assembly of the 30S ribosome, they are not necessary for the binding of S4 to 16S RNA. Taken with previous results, the domain of S4 involved in specific binding of 16S RNA can be confined to residues 47-103.


[Formation of the compact form of DNA in solution after reaction with spermidine].
The formation of compact particles from double-stranded DNA molecules in water-salt solutions containing spermidine was studied. It has been shown that in solutions of low ionic strength (0.01 M NaCl) DNA-spermidine complexes have the form of large particles which scatter UV-light. Electron micrographs show that such complexes formed at certain molar ratios spermidine/DNA may exist both as intermolecular aggregates and as toroidal particles 1500 A in diameter. The CD spectra of solutions containing DNA-spermidine complexes are characterized by the positive band (delta epsilon max = 10) at 265--270 nm. The appearance of the positive CD band may be caused by two factors: interaction between DNA and spermidine may lead to the alteration of the DNA secondary structure "in direction to A-form" or intermolecular aggregation, which may change the initial shape of the CD spectrum. The exclusion of spermidine molecules from DNA-spermidine complexes by Na+ ions in presence of poly(ethylene glycol) which occurs as the ionic strength increases from 0.01 to 0.3 does not lead to decompactization of DNA molecules but is accompained by the appearance of the intense negative CD band at 270 nm.


Chronic intraaneurysmal pressure measurement: an experimental method for evaluating the effectiveness of endovascular aortic aneurysm exclusion.
To evaluate and compare the intraaneurysmal pressure (IAP) after exclusion using two different endovascular grafts. Eight mongrel dogs had a 3 x 3 cm polytetrafluoroethylene (PTFE) aneurysm sewn as an interposition graft of the infrarenal aorta. A pressure transducer implanted into the aneurysm wall permitted continuous electronic IAP monitoring. Four aneurysms were excluded with a transluminally placed endovascular graft made of a PTFE graft and two Palmaz stents (PTFE-EG), three were excluded with a tantalum-Dacron endovascular graft (TD-EG), and one was surgically treated with a standard PTFE graft (PTFE-Surg). The dogs were observed for 18 to 50 days (mean, 37.5 days) and were evaluated after surgery with duplex and spiral computed tomographic scans. All grafts successfully excluded the aneurysms without perigraft channels or leaks as documented by arteriogram and duplex and computed tomographic scans. The mean IAPs after repair with all PTFE-EGs were significantly lower (p < 0.001) than the mean systemic pressures. In addition, the mean IAP reduction was significantly greater (p < 0.005) in the PTFE-EG group than in the TD-EG group. Aneurysm exclusion with PTFE-EG significantly lowered IAP, did so significantly better than the TD-EG, and approached the IAP reduction obtained by standard repair. Such pressure reduction is necessary for effective protection against aneurysm rupture.


Thyroid hormone promotes cell invasion through activation of furin expression in human hepatoma cell lines.
The objective of this study was to identify genes regulated by thyroid hormone (T(3)) and associated with tumor invasion. The gene encoding furin, as previously identified by cDNA microarray, is known to be up-regulated by T(3) treatment, and stimulated furin production occurs in thyroidectomized rats after administration of T(3). Presently, by using serial deletion of the promoter and EMSAs, the T(3) response element on the furin promoter was localized to the -6317/-6302 region. T(3)-mediated furin up-regulation was cooperative with TGF-beta because T(3) induction increased after Smad3/4 addition. Furthermore, the invasiveness of HepG2-thyroid hormone receptor (TR) cells was significantly increased by T(3) treatment, perhaps due to furin processing of matrix metalloproteinase-2 and -9. In addition, furin up-regulation either by stable overexpression or T(3) and/or TGF-beta induction was evident in severe-combined immune-deficient mice inoculated with HepG2-TRalpha1 cells. The HepG2-furin mice displayed a higher metastasis index and tumor size than HepG2-neo mice. Notably, the increased liver and lung tumor number or size in the hyperthyroid severe-combined immune-deficient mice as well as TGF-beta mice was attributed specifically to furin overexpression in the HepG2-TRalpha1 cells. Furthermore, this study demonstrated that furin overexpression in some types of hepatocellular carcinomas is TR dependent and might play a crucial role in the development of hepatocellular carcinoma. Thus, T(3) regulates furin gene expression via a novel mechanism or in cooperation with TGF-beta to enhance tumor metastasis in vitro and in vivo.


Cutting a long story short: reaction times in acute stroke are associated with longer term cognitive outcomes.
The viability and usefulness of cognitive assessment in acute stroke have been questioned, with practical challenges arising from the focal nature of neurological deficits as well as heterogeneity in arousal state. We aimed to test whether acute measures of attention correlate with attentional function at 3 months post-stroke. Patients with confirmed stroke completed 2 computerised cognitive tasks (CogState) within 2 weeks of stroke. The tasks were a simple reaction time task (Detection) and a choice reaction time task (Identification) that required a button press to visual stimuli (playing cards). Each task took approximately 4 min. The Montreal Cognitive Assessment (MoCA) and an extended neuropsychological battery were administered at 3 months post-stroke. Thirty-three patients (mean age 75.5 years, SD 11.9) participated in this preliminary study. Correlations indicated that both Detection speed (r=-0.73, p<0.001) and Identification speed (r=-0.61, p=0.007) at baseline were associated with attentional function at 3 months, as measured by established neuropsychological tests (Trails-A, Digit span, Digit symbol). In addition, Detection speed at baseline was correlated with total 3-month MoCA score (r=-0.54, p=0.012). Simple and brief computerised assessment of attentional function in acute stroke is possible and is related to longer term attentional and cognitive performance.


A T cell receptor V alpha domain expressed in bacteria: does it dimerize in solution?
To evaluate the potential for dimerization through a particular T cell receptor (TCR) domain, we have cloned the cDNA encoding a TCR V alpha from a hybridoma with specificity for the human immunodeficiency virus (HIV) envelope glycoprotein 120-derived peptide P18-110 (RGPGRAFVTI) bound to the murine major histocompatibility complex (MHC) class I molecule, H-2Dd. This cDNA was then expressed in a bacterial vector, and protein, as inclusion bodies, was solubilized, refolded, and purified to homogeneity. Yield of the refolded material was from 10 to 50 mg per liter of bacterial culture, the protein was soluble at concentrations as high as 25 mg/ml, and it retained a high level of reactivity with an anti-V alpha 2 monoclonal antibody. This domain was monomeric both by size exclusion gel chromatography and by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Circular dichroism spectra indicated that the folded V alpha domain had secondary structure similar to that of single immunoglobulin or TCR domains, consisting largely of beta sheet. Conditions for crystallization were established, and at least two crystal geometries were observed: hexagonal bipyramids that failed to diffract beyond approximately 6 A, and orthorhombic crystals that diffracted to 2.5 A. The dimerization of the V alpha domain was investigated further by solution nuclear magnetic resonance spectroscopy, which indicated that dimeric and monomeric forms of the protein were about equally populated at a concentration of 1 mM. Thus, models of TCR-mediated T cell activation that invoke TCR dimerization must consider that some V alpha domains have little tendency to form homodimers or multimers.


The epidemiological transition in Eastern and Western Europe: a historic natural experiment.
The continent of Europe has experienced remarkable changes in the past 25 years, providing scope for natural experiments that offer insight into the complex determinants of health. We analysed trends in life expectancy at birth in three parts of Europe, those countries that were members of the European Union (EU) prior to 2004, countries that joined the European Union since then, and the twelve countries that emerged from the Soviet Union to form the Commonwealth of Independent States (CIS). The contribution of deaths at different ages to these changes was assessed using Arriaga's method of decomposing changes in life expectancy. Europe remains divided geographically, with an East-West gradient. The former Soviet countries experienced a marked initial decline in life expectancy and have only recovered after 2005. However, the situation for those of working ages is little better than in 1990. The pre-2004 EU has seen substantial gains throughout the past 25 years, although there is some evidence that this may be slowing, or even reversing, at older ages. The countries joining the EU in 2004 subsequently began to see some improvements in the early 1990s, but have experienced larger gains since 2000. Europe offers a valuable natural laboratory for understanding the impact of political, economic, and social changes on health. While the historic divisions of Europe are still visible, there is also evidence that individual countries are doing better or worse than their neighbours, providing many lessons that can be learned from.


Exploring older care recipients' sleep status as a predictor for informal carer distress: evidence from New Zealand's interRAI home care assessment data.
Understanding factors affecting informal carers' well-being is important to support healthy ageing at home. Sleep disturbances of care recipients are increasingly recognised as affecting the well-being of both parties. This research assesses the relationship between indicators of care recipients' sleep status and carer distress, as well as carer distress with subsequent admission to residential aged care, using prospectively collected Home Care International Residential Assessment Instrument (interRAI-HC) assessment data. Data were sourced from 127 832 assessments conducted between 2012 and 2019 for people aged 55 years or older who had support from at least one informal carer. The majority (59.4%) of care recipients were female and 59.1% were defined as having cognitive impairment or dementia (CIoD). New Zealand. Logistic regression modelling was used to assess the independent relationships between indicators of care recipients' sleep status (difficulty sleeping and fatigue) and primary caregivers' distress (feeling overwhelmed or distressed). Kaplan meier curves illustrated the subsequent relationship between caregiver distress and care recipients' transitions to aged residential care. Care recipients' sleeping difficulty (32.4%) and moderate-severe fatigue (46.6%) were independently associated with caregiver distress after controlling for key demographic and health factors included in the assessment. Distress was reported by 39.9% of informal caregivers and was three times more likely among those supporting someone with a CIoD. Caregiver distress was significantly associated with care recipients' earlier admission into aged residential care. Indicators of sleep disturbance among care recipients are associated with increased likelihood of carer distress. This has implications for managing the overall home-care situation and long-term care needs, as well as the well-being of both parties. Findings will inform research and development of measures, services and interventions to improve the sleep and waking health of older people, including those with CIoD and family caregivers.


Light regulation of a SSRubisco-nos chimaeric gene: photoregulatory control sequences from a C3 plant function in cells of a CAM plant.
A SSRubisco-nos chimaeric gene has been constructed, in an oncogenic Ti-plasmid vector. A 900bp soybean SSRubisco upstream fragment, carrying CAAT and TATA boxes and transcription initiation point, was fused to the nos coding region, the fusion site being within the 5'-untranslated region. When this chimaeric construct was transferred to Kalanchoe cells, nos expression was shown to be light-regulated. Thus DNA sequences responsible for light-dark control of gene expression are wholly or partly contained within the 900bp soybean SSRubisco upstream region. Moreover, this is the first demonstration that photoregulatory elements in a gene derived from a C3 plant, function in cells of a plant exhibiting the CAM trait.


Saccade and vergence eye movements: a review of motor and premotor commands.
Neuropsychology examines the relationship between cognitive activity and corresponding cerebral conditions. At one end, psychophysics meticulously describes the details of behavior. At the other, physiology records brain cell activity during cognitive tasks. Bridging the two, neuropsychology establishes the neural correlate of behaviour when correlation methods are used, and extends to the critical neural substrate when a causal relationship can be established. Here we revisit the Hering-versus-Helmholtz controversy on binocular coordination from the psychophysician's description of combined saccade-vergence eye movements to the neurophysiological recording of motor and premotor neurons of the oculomotor neural circuitry. Whilst neo-Heringian psychophysicians and physiologists have accumulated arguments for separate saccade and vergence systems, at both the behavioral and the neural premotor levels, neo-Helmholtzians have also provided evidence for monocular programmed eye movements and commands at the premotor level. Bridging the two, we conclude that Hering and Helmholtz were both right. Importantly, the latter's viewpoint brings to the fore the importance of adaptive processes throughout life, in view of the neurobiological constraints emphasized by the former.


The adjacent dnaZ and dnaX genes of Escherichia coli are contained within one continuous open reading frame.
The dnaZ and dnaX loci of Escherichia coli have been genetically defined as separate genes, both of which are essential for DNA replication (1). The 2.1 kb region of DNA that complements mutations in both genes has a maximum coding capacity of approximately 80,000 daltons. Two protein products are produced from this region with molecular weights of 77,000 and 52,000 (2,3). We have sequenced a 2.7 kb fragment containing the dnaZ and dnaX genes and determined that it contains only one open reading frame of sufficient length to encode either of these proteins. This open reading frame may encode a protein of 71,147 daltons or of 68,451 daltons depending on which potential translational initiation codon is utilized. There are two transcriptional promoters preceding the gene as well as a ribosome binding site preceding the two potential initiation codons. Both the promoters and ribosome binding sites are predicted to be weak, perhaps contributing to the low expression of these genes.


Regulation of ion transport and energy metabolism enables certain coral genotypes to maintain calcification under experimental ocean acidification.
Cold-water corals (CWCs) are important foundation species in the world's largest ecosystem, the deep sea. They support a rich faunal diversity but are threatened by climate change and increased ocean acidification. As part of this study, fragments from three genetically distinct Lophelia pertusa colonies were subjected to ambient pH (pH = 7.9) and low pH (pH = 7.6) for six months. RNA was sampled at two, 4.5, and 8.5 weeks and sequenced. The colony from which the fragments were sampled explained most of the variance in expression patterns, but a general pattern emerged where upregulation of ion transport, required to maintain normal function and calcification, was coincident with lowered expression of genes involved in metabolic processes; RNA regulation and processing in particular. Furthermore, there was no differential expression of carbonic anhydrase detected in any analyses, which agrees with a previously described lack of response in enzyme activity in the same corals. However, one colony was able to maintain calcification longer than the other colonies when exposed to low pH and showed increased expression of ion transport genes including proton transport and expression of genes associated with formation of microtubules and the organic matrix, suggesting that certain genotypes may be better equipped to cope with ocean acidification in the future. While these genotypes exist in the contemporary gene pool, further stresses would reduce the genetic variability of the species, which would have repercussions for the maintenance of existing populations and the ecosystem as a whole.


Fast isogenic mapping-by-sequencing of ethyl methanesulfonate-induced mutant bulks.
Mapping-by-sequencing (or SHOREmapping) has revitalized the powerful concept of forward genetic screens in plants. However, as in conventional genetic mapping approaches, mapping-by-sequencing requires phenotyping of mapping populations established from crosses between two diverged accessions. In addition to the segregation of the focal phenotype, this introduces natural phenotypic variation, which can interfere with the recognition of quantitative phenotypes. Here, we demonstrate how mapping-by-sequencing and candidate gene identification can be performed within the same genetic background using only mutagen-induced changes as segregating markers. Using a previously unknown suppressor of mutants of like heterochromatin protein1 (lhp1), which in its functional form is involved in chromatin-mediated gene repression, we identified three closely linked ethyl methanesulfonate-induced changes as putative candidates. In order to assess allele frequency differences between such closely linked mutations, we introduced deep candidate resequencing using the new Ion Torrent Personal Genome Machine sequencing platform to our mutant identification pipeline and thereby reduced the number of causal candidate mutations to only one. Genetic analysis of two independent additional alleles confirmed that this mutation was causal for the suppression of lhp1.


Underdiagnosis of chronic obstructive pulmonary disease in Northern Sweden.
To assess underdiagnosis of chronic obstructive pulmonary disease. Two cross-sectional studies of respiratory symptoms and diseases in two population samples of the same age living in the same areas in northern Sweden were performed 6 years apart. In 1986, 5698 (86%) out of 6610 subjects aged 35-36, 50-51 and 65-66 years responded to a postal questionnaire. In 1992 an identical study was performed, and 5617 subjects (87%) out of 6434 responded. Lung function measurements were performed in stratified samples. Of the subjects diagnosed with chronic bronchitis only 25% in 1986 and 23% in 1992 had been diagnosed prior to the study as having chronic bronchitis, emphysema or chronic obstructive pulmonary disease (COPD). Chronic airflow limitation (CAL), used as a surrogate variable for COPD and defined as FEV1/VC <70% and FEV1 <80% of predicted value, was found in 171 subjects in 1986-1987 (12% of the examined subjects), and 166 subjects in 1993-1994 (11%). In 1986-1987, 26% of the subjects with CAL had been diagnosed as having chronic bronchitis or emphysema prior to the survey, while a diagnosis of either asthma, chronic bronchitis or emphysema, or use of asthma medicines, was found in 58%. The corresponding figures in 1993-1994 were 31% and 63%, respectively. The great majority of the subjects with CAL had recurrent wheeze, dyspnoea and chronic productive cough. Approximately 60% of the subjects with chronic airflow limitation had been diagnosed prior to the survey as having asthma, chronic bronchitis or emphysema, or were using asthma medicines. The results were similar in 1986-1987 and 1993-1994.


Participation rates by educational levels have diverged during 25 years in Finnish health examination surveys.
Declining participation rates in health examination surveys may impair the representativeness of surveys and introduce bias into the comparison of results between population groups if participation rates differ between them. Changes in the characteristics of non-participants over time may also limit comparability with earlier surveys. We studied the association of socio-economic position with participation, and its changes over the past 25 years. Occupational class and educational level are used as indicators of socio-economic position. Data from six cross-sectional FINRISK surveys conducted between 1987 and 2012 in Finland were linked to national administrative registers, which allowed investigation of the differences between survey participants and non-participants. Our results show that individuals with low occupational class or low level of education were less likely to participate than individuals with high occupational class or high level of education. Participation rates decreased in all subgroups of the population but the decline was fastest among those with low level of education. The differences in participation rates must be taken into account to avoid biased estimates because socio-economic position has also been shown to be strongly related to health, health behaviour and biological risk factors. Particular attention should be paid to the recruitment of the less-educated population groups.


The validity, reliability, and responsiveness of the modified Iowa Level of Assistance scale in hospitalized older adults in subacute care.
The objective of this study was to investigate the psychometric properties of the Modified Iowa Level of Assistance scale in hospitalized older adults in subacute care. A cohort, measurement-focused study. Fifty-eight older adults, aged 65 years and older, were recruited from a subacute rehabilitation hospital. Inter-rater reliability was established by having two physiotherapists independently assess each participant within 24-h of each other. Construct validity was established using "known-groups" validity, while concurrent validity was also examined by correlating modified Iowa Level of Assistance scores with the Elderly Mobility Scale. Responsiveness was assessed by examining the difference in modified Iowa Level of Assistance scores from admission to discharge. The mean age of participants was 82.8 years (SD 7.5; range 68-97). The modified Iowa Level of Assistance scale was found to be reliable, valid, and responsive in this sample of hospitalized older adults. It had excellent inter-rater reliability (intraclass correlation coefficient [2,1] 0.96; 95% confidence intervals (CI) 0.93, 0.98) and no systematic differences across the range of scores. The scale displayed a mean difference between two known groups of 11.4 points and correlated significantly and negatively with the Elderly Mobility Scale (Spearman's rho - 0.90). The modified Iowa Level of Assistance score also changed significantly over the course of the hospital admission with an effect size of 1.2. The modified Iowa Level of Assistance scale is a valid measure with excellent inter-rater reliability in hospitalized older adults. It is responsive to functional change during hospital admission and may be useful for routine outcome assessment for hospitalized older adults in subacute care. Implications for Rehabilitation The mILOA scale is a valid, reliable, and responsive outcome measure that can be used to quantify the gait and mobility impairments in hospitalized older adults in subacute care. For optimal reliability and responsiveness, consistent administration of the mILOA scale will be required particularly for higher level mobility tasks such as negotiating a step.


The Effect of Metacarpophalangeal Joint Hyperextension on Outcomes in the Surgical Treatment of Carpometacarpal Joint Arthritis.
Purpose In the surgical treatment of thumb carpometacarpal (CMC) joint arthritis, the effect of mild preoperative metacarpophalangeal (MCP) hyperextension on postoperative functional outcomes is unknown. We sought to examine outcomes after surgical treatment of CMC arthritis in patients with and without mild preexisting MCP deformity. Methods A retrospective review was conducted to analyze the functional outcomes of patients treated for CMC arthritis at a single institution from March 1998 to May 2009. All patients were treated with one of two standard CMC arthroplasty procedures-either ligament reconstruction tendon interposition (LRTI) or a Weilby procedure-and none had additional procedures to address MCP hyperextension. Pre- and postoperative assessments included pinch and grip strength, degree of MCP hyperextension, and thumb radial and palmar abduction. A t -test was used to assume unequal variances. Results A total of 203 patients were followed for an average of 27.3 months. Patients were divided into two groups: (1) patients without preoperative MCP hyperextension (167 patients) and (2) patients with mild but untreated preoperative MCP hyperextension (≤ 30 degrees; 36 patients). All patients underwent either a Weilby procedure (118 patients) or an LRTI; 85 patients). The main difference between techniques was the use of the abductor pollicis longus tendon as a post to secure the flexor carpi radialis (Weilby) or the use of a bone tunnel in the first metacarpal (LRTI). Analysis of the preoperative data showed no difference in the baseline parameters among both the groups, with the exception of MCP hyperextension. Postoperatively, neither the type of CMC procedure nor the presence of MCP hyperextension demonstrated any significant differences in key pinch, tip pinch, grip strength, and radial or palmar abduction of the thumb between the groups. Conclusion There were no statistically significant differences in improvement of functional outcomes after surgery when comparing patients without preoperative MCP hyperextension to patients with untreated MCP hyperextension of less than 30 degrees. Level of Evidence Level III, retrospective comparative study.


Roles of nitric oxide, nitrite and myoglobin on myocardial efficiency in trout (Oncorhynchus mykiss) and goldfish (Carassius auratus): implications for hypoxia tolerance.
The roles of nitric oxide synthase activity (NOS), nitrite and myoglobin (Mb) in the regulation of myocardial function during hypoxia were examined in trout and goldfish, a hypoxia-intolerant and hypoxia-tolerant species, respectively. We measured the effect of NOS inhibition, adrenaline and nitrite on the O(2) consumption rate and isometric twitch force development in electrically paced ventricular preparations during hypoxia, and measured O(2) affinity and nitrite reductase activity of the purified heart Mbs of both species. Upon hypoxia (9% O(2)), O(2) consumption and developed force decreased in both trout and goldfish myocardium, with trout showing a significant increase in the O(2) utilization efficiency, i.e. the ratio of twitch force to O(2) consumption, suggesting an increased anaerobic metabolism. NOS inhibition enhanced myocardial O(2) consumption and decreased efficiency, indicating that mitochondrial respiration is under a tone of NOS-produced NO. When trout myocardial twitch force and O(2) consumption are enhanced by adrenaline, this NO tone disappears. Consistent with its conversion to NO, nitrite reduced O(2) consumption and increased myocardial efficiency in trout but not in goldfish. Such a difference correlates with the lower O(2) affinity measured for trout Mb that would increase the fraction of deoxygenated heme available to catalyze the reduction of nitrite to NO. Whereas low-affinity trout Mb would favor O(2) diffusion within cardiomyocytes at high in vivo O(2) tensions, goldfish Mb having higher O(2) affinity and higher nitrite reductase activity appears better suited to facilitate O(2) diffusion and nitrite reduction in the heart during severe hypoxia, a condition particularly well tolerated by this species.


Functional domains of c-myc promoter binding protein 1 involved in transcriptional repression and cell growth regulation.
We initially identified c-myc promoter binding protein 1 (MBP-1), which negatively regulates c-myc promoter activity, from a human cervical carcinoma cell expression library. Subsequent studies on the biological role of MBP-1 demonstrated induction of cell death in fibroblasts and loss of anchorage-independent growth, reduced invasive ability, and tumorigenicity of human breast carcinoma cells. To investigate the potential role of MBP-1 as a transcriptional regulator, a chimeric protein containing MBP-1 fused to the DNA binding domain of the yeast transactivator factor GAL4 was constructed. This fusion protein exhibited repressor activity on the herpes simplex virus thymidine kinase promoter via upstream GAL4 DNA binding sites. Structure-function analysis of mutant MBP-1 in the context of the GAL4 DNA binding domain revealed that MBP-1 transcriptional repressor domains are located in the N terminus (amino acids 1 to 47) and C terminus (amino acids 232 to 338), whereas the activation domain lies in the middle (amino acids 140 to 244). The N-terminal domain exhibited stronger transcriptional repressor activity than the C-terminal region. When the N-terminal repressor domain was transferred to a potent activator, transcription was strongly inhibited. Both of the repressor domains contained hydrophobic regions and had an LXVXL motif in common. Site-directed mutagenesis in the repressor domains indicated that the leucine residues in the LXVXL motif are required for transcriptional repression. Mutation of the leucine residues in the common motif of MBP-1 also abrogated the repressor activity on the c-myc promoter. In addition, the leucine mutant forms of MBP-1 failed to suppress cell growth in fibroblasts like wild-type MBP-1. Taken together, our results indicate that MBP-1 is a complex cellular factor containing multiple transcriptional regulatory domains that play an important role in cell growth regulation.


Dehydration of water/pyridine mixtures by pervaporation using cellulose acetate/ polyacrylonitrile blend membrane.
Cellulose acetate/ polyacrylonitrile (CA/PAN) membranes were prepared and used to separate pyridine / water mixtures by pervaporation. The membranes were characterized through SEM. The effects of feed concentration, operation temperature and downstream pressure on the separation performance were evaluated. Experimental results indicated the increase of operation temperature could raise the permeation flux and the separation factor, while increasing feed concentration and downstream pressure would raise the separation factor and decrease the permeation flux. Under the conditions that pyridine solution was 99 wt.%, operation temperature was 323 K and downstream pressure was 20 mmHg, the CA/PAN blend membrane showed its best separation performance that the permeation flux was 56.g.m-2 h-1 and the separation factor was 182.


A systematic approach to selecting and evaluating instructional materials.
This article provides an overview of the process of selecting and evaluating instructional materials. The reader is given specific criteria to be used in assessing the content, instructional design, technical production, and packaging of instructional materials.


The influence of different types of preparation (espresso and brew) on coffee aroma and main bioactive constituents.
Coffee is one of the most popular hot drinks in the world; it may be prepared by several methods, but the most common forms are boiled (brew) and pressurized (espresso). Analytical studies on the substances responsible for the pleasant aroma of roasted coffee have been carried out for more than 100 years. Brew coffee and espresso coffee (EC) have a different and peculiar aroma profile, demonstrating the importance of the brewing process on the final product sensorial quality. Concerning bioactive compounds, the extraction mechanism plays a crucial role. The differences in the composition of coffee brew in chlorogenic acids and caffeine content is the result of the different procedures of coffee preparation. The aim of the present review is to detail how the brewing process affects coffee aroma and composition.


Who reports noticing and using calorie information posted on fast food restaurant menus?
Identify consumer characteristics that predict seeing and using calorie information on fast food menu boards. Two separate data collection methods were used in Philadelphia during June 2010, several weeks after calorie labeling legislation went into effect: (1) point-of-purchase survey and receipt collection conducted outside fast food restaurants (N = 669) and (2) a random digit dial telephone survey (N = 702). Logistic regressions were used to predict the odds of reporting seeing, and of reporting seeing and being influenced by posted calorie information. Approximately 35.1% of point-of-purchase and 65.7% of telephone survey respondents reported seeing posted calorie information, 11.8% and 41.7%, respectively, reported that the labels influenced their purchasing decisions, and 8.4% and 17% reported they were influenced in a healthful direction. BMI, education, income, gender, consumer preferences, restaurant chain, and frequency of visiting fast food restaurants were associated with heterogeneity in the likelihood of reporting seeing and reporting seeing and using calorie labels. Demographic characteristics and consumer preferences are important determinants in the use of posted calorie information. Future work should consider the types of consumers this information is intended for, and how to effectively reach them.


Ambulatory non-convulsive status epilepticus evolving into a malignant form.
We retrospectively analysed the clinical characteristics, electroencephalogram (EEG) records, brain magnetic resonance imaging (MRI) scans, antiepileptic therapy and prognosis of a case series with ambulatory non-convulsive status epilepticus (NCSE) which evolved into a malignant form (mNCSE). mNCSE was defined as NCSE that continues or recurs five days or more after the onset of general anaesthesia, including those cases where NCSE recurs upon reduction or withdrawal of anaesthetic therapy. Four women and two men were studied. The mean age was 42.8 years (range: 19-63 years). Two of six patients had a previous diagnosis of epilepsy. Four patients died. Two patients had a good outcome with return to consciousness and activities of daily life, and one of these subjects developed temporal lobe epilepsy. In four patients, the cause of mNCSE was encephalitis. Clinical presentation was complex partial status epilepticus (CPSE) in three patients and generalised NCSE (GNCSE) in the other three. Two of the latter had encephalitis and one was diagnosed with progressive myoclonus epilepsy (PME) of Lafora type. The mean duration of the NCSE episode was 47.5 days (range: 9-139 days; SD: 53.1). In three patients, continuous or rhythmic focal epileptiform discharges were the EEG pattern at onset. In the other three, continuous rhythmic generalised spike-wave, polyspike-wave or sharp slow-wave complexes were observed. Antiepileptic treatment was heterogeneous and patients were treated with an average of 6.0 AEDs (range: 3-10; SD: 3.0). In summary, mNCSE is a severe epileptic condition that occurs often in the context of encephalitis or pre-existing epilepsy. Both CPSE and GNCSE may occur. Although high mortality is associated with mNCSE, some patients may survive with normal or good recovery.


HPV disease transmission protection and control.
Human papillomaviruses (HPVs) represent a large collection of viral types associated with significant clinical disease of cutaneous and mucosal epithelium. HPV-associated cancers are found in anogenital and oral mucosa, and at various cutaneous sites. Papillomaviruses are highly species and tissue restricted, and these viruses display both mucosotropic, cutaneotropic or dual tropism for epithelial tissues. A subset of HPV types, predominantly mucosal, are also oncogenic and cancers with these HPV types account for more than 200,000 deaths world-wide. Host control of HPV infections requires both innate and adaptive immunity, but the viruses have developed strategies to escape immune detection. Viral proteins can disrupt both innate pathogen-sensing pathways and T-cell based recognition and subsequent destruction of infected tissues. Current treatments to manage HPV infections include mostly ablative strategies in which recurrences are common and only active disease is treated. Although much is known about the papillomavirus life cycle, viral protein functions, and immune responsiveness, we still lack knowledge in a number of key areas of PV biology including tissue tropism, site-specific cancer progression, codon usage profiles, and what are the best strategies to mount an effective immune response to the carcinogenic stages of PV disease. In this review, disease transmission, protection and control are discussed together with questions related to areas in PV biology that will continue to provide productive opportunities of discovery and to further our understanding of this diverse set of human viral pathogens.


Preferred and actual participation roles during health care decision making in persons with cancer: a systematic review.
The preferred and actual participation roles during decision making have been studied over the past two decades; however, there is a lack of evidence on the degree of match between patients' preferred and actual participation roles during decision making. A systematic review was carried out to identify published studies that examined preferred and actual participation roles and the match between preferred and actual roles in decision making among patients with cancer. PubMed (1966 to January 2009), PsycINFO (1967 to January 2009), and CINAHL (1982 to January 2009) databases were searched to access relevant medical, psychological, and nursing literature. Twenty-two studies involving patients with breast, prostate, colorectal, lung, gynecological, and other cancers showed discrepancies between preferred and actual roles in decision making. These groups of patients wanted a more shared or an active role versus a less passive role. Across all cancer types, patients wanted more participation than what actually occurred. Research to date documents a pervasive mismatch between patients' preferred and actual roles during decision making. Yet, there is lack of innovative interventions that can potentially increase matching of patients' preferred and actual role during decision making. Role preferences are dynamic and vary greatly during decision making, requiring regular clinical assessment to meet patients' expectations and improve satisfaction with treatment decisions.


Metasurface-enabled broadband beam splitters integrated with quarter-wave plate functionality.
Conventional beam splitters and wave plates, while being essential components in diverse optical systems, require considerable space, especially when used in combination. Here, we designed and experimentally demonstrated metasurface-enabled efficient broadband beam splitters integrated with quarter-wave plate (QWP) functionality for simultaneous power splitting and circular-to-linear polarization conversion in the near-infrared range. By utilizing two different gap-plasmon meta-atoms, which function as QWPs performing efficient circular-to-linear polarization conversion and provide the phase difference of π between reflected linearly polarized beams, we designed a metasurface that completely suppress the specular reflection (zero-order diffraction) and second-order diffraction, while ensuring efficient and equal beam splitting of a circularly polarized wave into two reflected beams with predesigned directions and well-defined linear-polarization states in the wavelength range of 750-950 nm. The fabricated metasurface exhibits excellent performance of circular-to-linear conversion and power splitting, with efficient suppression of specular reflection (<1%) and splitting efficiencies above 50% for both right and left circularly polarized excitation at the design wavelength of λ = 850 nm. By enabling the combined functionalities of a conventional beam splitter and a QWP, our approach opens up new prospects for advanced research and applications targeting photonics integration and miniaturization.


Functional MRI of working memory in paediatric head injury.
A case study examining the recovery of a 9 year old boy who sustained a severe head injury is reported. The subject sustained damage to the left parietal-occipital and right frontal-parietal regions. Structural and functional imaging and cognitive data were collected at the time of injury and 1 year post-injury. Cognitive assessment revealed improvement over time. Functional imaging at the time of injury revealed minimal activation in the right posterior temporal region. Imaging 1 year post-injury revealed increased activation in the right pre-frontal cortex, bilateral pre-motor cortex and bilateral posterior parietal cortex. This activation pattern is consistent with the performance of unaffected individuals on working memory tasks. These findings differ from those in the adult literature and suggest an alternative pattern of recovery of function in children.


MetNetComp: Database for Minimal and Maximal Gene-deletion Strategies for Growth-coupled Production of Genome-scale Metabolic Networks.
Growth-coupled production, in which cell growth forces the production of target metabolites, plays an essential role in the production of substances by microorganisms. The strains are first designed using computational simulation and then validated by biological experiments. In the simulations, gene-deletion strategies are often necessary because many metabolites are not produced in the natural state of the microorganisms. However, such information is not available for many metabolites owing to the requirement of heavy computation, especially when many gene deletions are required for genome-scale models. A database for such information will be helpful. However, developing such a database is not straightforward because heavy computation and the existence of replaceable genes render difficulty in efficient enumeration. In this study, the author developed efficient methods for enumerating minimal and maximal gene-deletion strategies and a web-based database system, MetNetComp (https://metnetcomp.github.io/database1/indexFiles/index.html). MetNetComp provides information on (1) a total of 85,611 gene-deletion strategies excluding apparent duplicate counting for replaceable genes for 1,735 target metabolites, 11 constraint-based models, and 10 species; (2) necessary substrates and products in the process; and (3) reaction rates that can be used for visualization. MetNetComp is helpful for strain design and for new research paradigms using machine learning.


Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19).
On March 11, 2020, the World Health Organization declared the worldwide spread of the infectious disease COVID-19, caused by a new strain of coronavirus, SARS-CoV-2, as a pandemic. Like in all other infectious diseases, the host immune system plays a key role in our defense against SARS-CoV-2 infection. However, viruses are able to evade the immune attack and proliferate and, in susceptible individuals, cause severe inflammatory response known as cytokine storm, particularly in the lungs. The advancement in our understanding of the mechanisms underlying the host immune responses promises to facilitate the development of approaches for prevention or treatment of diseases. Components of immune system, such as antibodies, can also be used to develop sensitive and specific diagnostic methods as well as novel therapeutic agents. In this review, we summarize our knowledge about how the host mounts immune responses to infection by SARS-CoV-2. We also describe the diagnostic methods being used for COVID-19 identification and summarize the current status of various therapeutic strategies, including vaccination, being considered for treatment of the disease.


Pain as a symptom of peripheral nerve sheath tumors: clinical significance and future therapeutic directions.
Tumors arising from the supporting cells of peripheral nerve sheaths are relatively uncommon neoplasms, and as such many clinicians are unfamiliar with the details of their presentation, diagnosis and management. Further, little is known regarding the pathogenesis of these tumors, how they cause symptoms, and how to treat these symptoms. One classic symptom of peripheral nerve tumors is pain, however there has been little formal discussion regarding the significance of pain in this setting. Here we present a brief review of the clinical significance of pain, its relevance in pre-operative planning for the treatment of these tumors, and what is known regarding the molecular mechanisms of pain generation by these tumors.


Appreciating Complexity in Adolescent Self-Harm Risk Factors: Psychological Profiling in a Longitudinal Community Sample.
Past research identifies a number of risk factors for adolescent self-harm, but often fails to account for overlap between these factors. This study investigated the underlying, broader concepts by identifying different psychological profiles among adolescents. We then compared new self-harm rates over a six-month period across different psychological profiles. Australian high school students (n = 326, 68.1% female) completed a questionnaire including a broad range of psychological and socioenvironmental risk and protective factors. Non-hierarchical cluster analysis produced six groups with different psychological profiles at baseline and rate of new self-harm at follow-up. The lowest rate was 1.4% in a group that appeared psychologically healthy; the highest rate was 37.5% in a group that displayed numerous psychological difficulties. Four groups with average self-harm had varied psychological profiles including low impulsivity, anxiety, impulsivity, and poor use of positive coping strategies. Identifying multiple profiles with distinct psychological characteristics can improve detection, guide prevention, and tailor treatment.


Variation in Arabidopsis developmental responses to oomycete infection: resilience vs changes in life history traits.
Although plant resistance to aggressors has been well described, there is still little knowledge about the mechanisms underlying their tolerance to pathogens. Tolerance often appears to be mediated by changes in life history traits, shifting host resource investment from growth to reproduction, but whether host phenotype modifications induced after attack are adaptive is not always clear. Here, we investigated the details of the impact of Hyaloperonospora arabidopsidis infection on several biomass, phenology and architectural traits of Arabidopsis thaliana, for three pathogen genotypes and three host plant genotypes that have been shown previously to differ greatly in fecundity and tolerance to infection. We found that, although host genotype explains most of the variance in life history traits, these three lines differ critically in their response to infection, with delays and biomass losses at bolting, together with changes in inflorescence architecture, observed at one extreme host line, and an advantage at bolting for infected plants and no inflorescence alteration for the other. These results suggest that the differences in tolerance observed previously in this pathosystem do not involve plasticity in inflorescence architecture, but may arise from induced changes at the vegetative stage, before plant transition to reproduction.


Evaluation of students' motivation during the gamification of electrocardiogram interpretation learning.
The quality of the training of medical students is one of the guarantors of the proper functioning of our health system. Gamification is an innovative educational pedagogical method that stimulates the pleasure of learning and encourages learner motivation. To evaluate the subjective and external motivations and academic self-efficacy of DCEM1 students by playing with TD sessions designed to learn the systematic interpretation of rhythm disorders on surface ECGs using playing cards. It was a descriptive, cross-sectional study. Three successive groups of 25 students each took part in this study which took place at the Faculty of Medicine of Tunis. Each group was subdivided into 5 subgroups. During the TD session, the same 18 playing cards are distributed to each subgroup, and various wide and thin QRS tachycardia ECG plots are projected successively. Each subgroup should collect playing cards related to the methodical interpretation of each ECG trace and establish the final diagnosis of rhythm disorder. At the end of the pedagogical training, an anonymous self-assessment questionnaire to measure the types of motivation and academic self-efficacy was submitted to the students. Seventy-five students participated in our study. They were mostly female (sex ratio = 4). Gamification learning using playing cards has generated learners' intrinsic motivation (5.89 ± 0.97), allowing them to feel more confident in themselves, capable of acquiring new skills. Regarding extrinsic motivation, having good results on the exam was not their main concern (4.34 ± 1.23). This learning method has created a feeling of self-efficacy among our learners (5,004 ± 0,98). Indeed, they proved to be able to assimilate the fundamental notions of the course (5.86 ± 1.26), to understand the most complex material of the course (5 ± 1.55) and to acquire the competences targeted by this course (5.41 ± 0.5 ). Finally, all learners were satisfied with the method of gamification learning using playing cards. They recommended that this method be generalized throughout all ECG sessions. Gamification learning seems to be an effective and appropriate approach to teaching in the medical field since it allows to associate the notion of pleasure and the act of learning and stimulating motivation and self-efficacy learners.


Friendship Quality and Gender Differences in Association With Cyberbullying Involvement and Psychological Well-Being.
Current literature has documented the detrimental effects of cyberbullying which include a range of internalizing and externalizing problems for those involved. Although critical, this research can sometimes ignore social-ecological aspects of a child's life that can potentially 'buffer' the negative psychological effects of such involvement. With this in mind, this cross-sectional investigation of 12-16 year olds [M(SD): 13.5(1) years] in Ireland focused on the role of friendship quality and gender in association with cyberbullying involvement and psychological well-being (N = 2410). The Cyberbullying and Online Aggression Scale was used to measure cyber perpetration and victimization. A modified version of the Cambridge Friendship Questionnaire was included to investigate peer friendship quality. Finally, the Moods and Feeling Questionnaire and the Strengths and Difficulties Questionnaire were chosen to provide a measurement of psychological well-being. Prevalence rates for various types of cyberbullying roles (cyber bullies, victims and bully/victims) are presented, as well as differences for psychological well-being, friendship quality and cyberbullying involvement. In addition, regression models were used to determine the associations between gender, age, friendship quality and involvement in cyberbullying with psychological well-being. The results are considered in terms of the current literature and directions for future research are suggested.


A randomized placebo-control trial of the acute effects of oxygen supplementation on exercise hemodynamics, autonomic modulation, and brain oxygenation in patients with pulmonary hypertension.
The integrative physiological effects of O2 treatment on patients with pulmonary hypertension (PH) during exercise, have not been fully investigated. We simultaneously evaluated, for the first time, the effect of oxygen supplementation on hemodynamic responses, autonomic modulation, tissue oxygenation, and exercise performance in patients with pulmonary arterial hypertension (PAH)/Chronic Thromboembolic PH(CTEPH). In this randomized, cross-over, placebo-controlled trial, stable outpatients with PAH/CTEPH underwent maximal cardiopulmonary exercise testing, followed by two submaximal trials, during which they received supplementary oxygen (O2) or medical-air. Continuous, non-invasive hemodynamics were monitored via photophlythesmography. Cerebral and quadriceps muscle oxygenation were recorded via near-infrared spectroscopy. Autonomic function was assessed by heart rate variability; root mean square of successive differences (RMSSD) and standard-deviation-Poincare-plot (SD1) were used as indices of parasympathetic output. Baroreceptor sensitivity (BRS) was assessed throughout the protocols. Nine patients (51.4 ± 9.4 years) were included. With O2-supplementation patients exercised for longer (p = 0.01), maintained higher cerebral oxygenated hemoglobin (O2Hb;p = 0.02) levels, exhibited an amelioration in cortical deoxygenation (HHb;p = 0.02), and had higher average cardiac output (CO) during exercise (p < 0.05), compared to medical air; with no differences in muscle oxygenation. With O2-supplementation patients exhibited higher BRS and sample-entropy throughout the protocol (p < 0.05) vs. medical air, and improved the blunted RMSSD, SD1 responses during exercise (p = 0.024). We show that O2 administration improves BRS and autonomic function during submaximal exercise in PAH/CTEPH, without significantly affecting muscle oxygenation. The improved autonomic function, along with enhancements in cardiovascular function and cerebral oxygenation, probably contributes to increased exercise tolerance with O2-supplementation in PH patients.


Quantitative analysis of protein synthesis in mouse embryos. I. Extensive reprogramming at the one- and two-cell stages.
A quantitative, high-resolution, two-dimensional gel protein database has been constructed for the mouse embryo. This database has been used to obtain a detailed accounting of the amount and relative timing of changes in protein synthesis that occur during the 1-, 2-, and 4-cell stages along with a description of the most prevalent developmentally regulated patterns of synthesis. We find that during these early stages of development the pattern of proteins synthesized changes to a much greater extent than previously appreciated. During the 1- and 2-cell stages, the majority (60% and 85%, respectively) of the analyzed proteins exhibit twofold or greater changes in their rates of synthesis. The periods of greatest change are the late 1-cell and mid 2-cell stages, during which an extensive remodelling of protein synthetic pattern occurs that is largely complete by 15 h following the first cleavage. Once this reprogramming is complete, very little change is observed during the late 2-cell and 4-cell stages. Cluster analysis of individual protein synthesis patterns reveals a limited number of coordinately regulated protein sets that are responsible for most of the changes observed during the 1- and 2-cell stages. During the 2-cell stage, one third of the proteins increase by an average of fivefold, another third decrease by an average of sevenfold, and 10% undergo transient changes in rates of synthesis. These patterns reflect the switch from zygotic to maternal mRNA utilization following transcriptional activation.(ABSTRACT TRUNCATED AT 250 WORDS)