[Psychological mechanisms of refusal reactions in schizophrenic patients].
The psychological study is based on the clinical typology of refusal reactions (RR) in schizophrenic patients--"capitulation", "avoidance", "absenteism". Seventy patients with RR, mean age 27 years, 25 women, 45 men, were examined with the use of a number of psychological methods. The findings prove the hypothesis on the disturbances of motivation as a psychological mechanism of RR in schizophrenic patients. Deficiency is related to functions of the motivational process: incentive function, goal achievement, sense making and strengthened by trait anxiety and desize to avoid danger. The main factor promoting RR formation is basic motivation deficiency caused by endogenous process (schizophrenia). A mechanism of capitulation reaction formation is closely related to expectation of failure and refusal from acting as an opportunity to preserve self-estimation; avoidance reaction is characterized by significant disturbance of the motivation at the stage of incentive, goal achievement and sense making. Motivation deficiency in patients with absenteism reactions is predominantly associated with an specific individual's sense.


A Descriptive Study of Television News Coverage of Tobacco in the United States: Frequency of Topics, Frames, Exemplars, and Efficacy.
There is a positive correlation between recall of tobacco-related television news and perceived risks of smoking and thoughts about quitting. The authors used Cision US, Inc., to create a sampling frame (N = 61,027) of local and national television news coverage of tobacco from October 1, 2008, to September 30, 2009, and to draw a nationally representative sample (N = 730) for content analysis. The authors conducted a descriptive study to determine the frequency and proportion of stories containing specified tobacco topics, frames, sources, and action messages, and the valence of the coverage. Valence was generally neutral; 68% of stories took a balanced stance, with 26% having a tenor supportive of tobacco control and 6% opposing tobacco control. The most frequently covered topics included smoking bans (n = 195) and cessation (n = 156). The least covered topics included hookah (n = 1) and menthol (n = 0). The majority of coverage lacked quoting any source (n = 345); government officials (n = 144) were the most quoted sources. Coverage lacked action messages or resources; 29 stories (<4%) included a message about cessation or advocacy, and 8 stories (1%) contained a resource such as a quitline. Television news can be leveraged by health communication professionals to increase awareness of underrepresented topics in tobacco control.


Common microscopic structural origin for water's thermodynamic and dynamic anomalies.
Water displays a vast array of unique properties, known as water's anomalies, whose origin remains subject to hot debate. Our aim in this article is to provide a unified microscopic physical picture of water's anomalies in terms of locally favored structures, encompassing both thermodynamic and dynamic anomalies, which are often attributed to different origins. We first identify locally favored structures via a microscopic structural descriptor that measures local translational order and provide direct evidence that they have a hierarchical impact on the anomalies. At each state point, the strength of thermodynamic anomalies is directly proportional to the amount of locally favored structures, while the dynamic properties of each molecule depend on the local structure surrounding both itself and its nearest neighbors. To incorporate this, we develop a novel hierarchical two-state model. We show by extensive simulations of two popular water models that both thermodynamic and kinetic anomalies can be almost perfectly explained by the temperature and pressure dependence of these local and non-local versions of the same structural descriptor, respectively. Moreover, our scenario makes three unique predictions in supercooled water, setting it apart from other scenarios: (1) Presence of an "Arrhenius-to-Arrhenius" crossover upon cooling, as the origin of the apparent "fragile-to-strong" transition; (2) maximum of dynamic heterogeneity around 20 K below the Widom line and far above the glass transition; (3) violation of the Stokes-Einstein-Debye relation at ∼2T g, rather than 1.2T g typical of normal glass-formers. These predictions are verified by recent measurement of water's diffusion at very low temperatures (point 1) and discoveries from our extensive simulations (points 2-3). We suggest that the same scenario may generally apply to water-like anomalies in liquids tending to form locally favored structures, including not only other important tetrahedral liquids such as silicon, germanium, and silica, but also metallic and chalcogenide liquids.


Development of Next-Generation Nutritionally Fortified Plant-Based Milk Substitutes: Structural Design Principles.
Consumers are increasingly interested in decreasing their dietary intake of animal-based food products, due to health, sustainability, and ethical concerns. For this reason, the food industry is creating new products from plant-based ingredients that simulate many of the physicochemical and sensory attributes associated with animal-derived foods, including milk, eggs, and meat. An understanding of how the ingredient type, amount, and organization influence the desirable physicochemical, sensory, and nutritional attributes of these plant-based foods is required to achieve this goal. A potential problem with plant-based diets is that they lack key micronutrients, such as vitamin B12, vitamin D, calcium, and ω-3 fatty acids. The aim of this review is to present the science behind the creation of next-generation nutritionally fortified plant-based milk substitutes. These milk-like products may be formed by mechanically breaking down certain plant materials (including nuts, seeds, and legumes) to produce a dispersion of oil bodies and other colloidal matter in water, or by forming oil-in-water emulsions by homogenizing plant-based oils and emulsifiers with water. A brief overview of the formulation and fabrication of plant-based milks is given. The relationship between the optical properties, rheology, and stability of plant-based milks and their composition and structure is then covered. Approaches to fortify these products with micronutrients that may be missing from a plant-based diet are also highlighted. In conclusion, this article highlights how the knowledge of structural design principles can be used to facilitate the creation of higher quality and more sustainable plant-based food products.


Potentiation by the lithium ion of morphogenetic responses to a Xenopus inducing factor.
We have cultured explants of Xenopus blastular animal cap tissue from embryos that had received an earlier treatment with LiCl and from their untreated siblings, in various concentrations of XTC-cell-derived mesoderm-inducing factor (XTC-MIF, Smith, 1987; Smith et al. 1988). The pretreatment with lithium that we used transforms later morphogenesis in the whole embryo to give radialized body forms with anterior/dorsal levels of structure grossly over-represented. In addition, animal caps from 'Li+' embryos were allowed to develop without exposure to in vitro MIF (Li+ controls) and compared with normal uninduced control explants, and explants were made from normal early blastulae but given various initial treatments with LiCl in culture. The results confirm that the lithium ion itself will not induce mesoderm in competent, animal cap tissue of Xenopus. It does, however, enhance the responsiveness of this tissue to XTC-MIF, in a way that parallels its recently reported effect in the case of another mesoderm inducer of different character, bFGF (Slack et al. 1988). The effects observed are sufficient to imply that the altered body pattern that follows lithium treatment, in whole embryos, could be caused by modulation of the responses to an unaltered pattern of in situ inductive stimuli. We also observe evidence that appreciable inductive signals reach animal pole tissue beyond the limits of mesoderm formation in normal development. Relatively low concentrations of MIF prevent the development of an epidermis-specific marker in dissociated blastular animal cap cells (Symes et al. 1988). When such experiments are repeated in relation to the lithium pretreatment of embryos, such treatment is seen to have sensitized the cell population, so that the MIF concentration range that assures complete suppression of the marker is reduced. The results are discussed in relation to induction considered as pattern formation.


Science-specialty literatures their legendary contemporary polarity, based on the transmission of information between generations.
Each of fifteen scientific specialty fields was represented by a journal and the percent of "legendary" papers (those with at least one reference twenty-five or more years old) was calculated for each field. Non-legendary papers were designated as "contemporary". A historical divergence was uncovered when the highly legendary field, physiology, was compared with the highly contemporary field, microbiology, both fields being moderately contemporary in 1922. The legendary contemporary field characteristics of a field are useful for estimating libraries' requirements for back holdings and for appraising literature searches.


Environmental Enrichment Mitigates Age-Related Metabolic Decline and Lewis Lung Carcinoma Growth in Aged Female Mice.
Aging is a complex physiological process that leads to the progressive decline of metabolic and immune function, among other biological mechanisms. As global life expectancy increases, it is important to understand determinants of healthy aging-including environmental and genetic factors-and thus slow the onset or progression of age-related disease. Environmental enrichment (EE) is a housing environment wherein laboratory animals engage with complex physical and social stimulation. EE is a prime model to understand environmental influences on aging dynamics, as it confers an antiobesity and anticancer phenotype that has been implicated in healthy aging and health span extension. Although EE is frequently used to study malignancies in young mice, fewer studies characterize EE-cancer outcomes in older mice. Here, we used young (3-month-old) and aged (14-month-old) female C57BL/6 mice to determine whether EE would be able to mitigate age-related deficiencies in metabolic function and thus alter Lewis lung carcinoma (LLC) growth. Overall, EE improved metabolic function, resulting in reduced fat mass, increased lean mass, and improved glycemic processing; many of these effects were stronger in the aged cohort than in the young cohort, indicating an age-driven effect on metabolic responses. In the aged-EE cohort, subcutaneously implanted LLC tumor growth was inhibited and tumors exhibited alterations in various markers of apoptosis, proliferation, angiogenesis, inflammation, and malignancy. These results validate EE as an anticancer model in aged mice and underscore the importance of understanding environmental influences on cancer malignancy in aged populations. PREVENTION RELEVANCE: Environmental enrichment (EE) serves as a model of complex physical and social stimulation. This study validates EE as an anticancer intervention paradigm in aged mice and underscores the importance of understanding environmental influences on cancer malignancy in aged populations.


Determination of effective miRNAs in wound healing in an experimental Rat Model.
The larvae of Lucilia sericata have been used for centuries as medicinal maggots in the healing of wounds. The present study aimed to screen potential microRNAs related to ES-induced wound healing in rat skin wounds and to investigate the potential mechanisms contributing to accelerated wound healing. Healthy, male, 12 weeks old Wistar albino rats weighing 250-300 g were supplied by the Animal Experimental Center. All animal studies were performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals. Wistar albino rats were treated by ES after post wounding and the differentially expressed miRNAs in wound biopsies were screened by microarray analysis at the end of treatments for 4,7 and 10 days. In addition, bioinformatics approaches were used to identify the potential target genes of differentially expressed miRNAs and the functions of their target genes. We found a significant up-regulation of rno-miR-99a* and rno-mir-877 in response to ES treatment. Further investigation of rno-miR-99a* and rno-mir-877 and their target genes (TGFa, TNF, TAGLN, MAPK1, MMP-9) implicated in present study could provide new insight for an understanding lead to the development of new treatment strategies. The identified miRNAs can be new biomarkers for ES- induced wound healing.


Pharmacodynamic effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, from a randomized study in patients with type 2 diabetes.
This randomized, double-blind, placebo-controlled, single and multiple ascending-dose study evaluated the pharmacodynamic effects and safety/tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes. Patients (N = 116) discontinued their antihyperglycemic medications 2 weeks before randomization. Patients received canagliflozin 30, 100, 200, or 400 mg once daily or 300 mg twice daily, or placebo at 2 study centers in the United States and Germany, or canagliflozin 30 mg once daily or placebo at 1 study center in Korea, while maintaining an isocaloric diet for 2 weeks. On Days -1, 1, and 16, urinary glucose excretion (UGE), plasma glucose (PG), fasting PG (FPG), and insulin were measured. The renal threshold for glucose (RTG) was calculated from UGE, PG, and estimated glomerular filtration rate. Safety was evaluated based on adverse event (AE) reports, vital signs, electrocardiograms, clinical laboratory tests, and physical examinations. Canagliflozin increased UGE dose-dependently (∼80-120 g/day with canagliflozin ≥100 mg), with increases maintained over the 14-day dosing period with each dose. Canagliflozin dose-dependently decreased RTG, with maximal reductions to ∼4-5 mM (72-90 mg/dL). Canagliflozin also reduced FPG and 24-hour mean PG; glucose reductions were seen on Day 1 and maintained over 2 weeks. Plasma insulin reductions with canagliflozin were consistent with observed PG reductions. Canagliflozin also reduced body weight. AEs were transient, mild to moderate in intensity, and balanced across groups; 1 canagliflozin-treated female reported an episode of vaginal candidiasis. Canagliflozin did not cause hypoglycemia, consistent with the RTG values remaining above the hypoglycemia threshold. At Day 16, there were no clinically meaningful changes in urine volume, urine electrolyte excretion, renal function, or routine laboratory test values. Canagliflozin increased UGE and decreased RTG, leading to reductions in PG, insulin, and body weight, and was generally well tolerated in patients with type 2 diabetes. ClinicalTrials.gov NCT00963768.


Musical activity and emotional competence - a twin study.
The hypothesis was tested that musical activities may contribute to the prevention of alexithymia. We tested whether musical creative achievement and musical practice are associated with lower alexithymia. 8000 Swedish twins aged 27-54 were studied. Alexithymia was assessed using the Toronto Alexithymia Scale-20. Musical achievement was rated on a 7-graded scale. Participants estimated number of hours of music practice during different ages throughout life. A total life estimation of number of accumulated hours was made. They were also asked about ensemble playing. In addition, twin modelling was used to explore the genetic architecture of the relation between musical practice and alexithymia. Alexithymia was negatively associated with (i) musical creative achievement, (ii) having played a musical instrument as compared to never having played, and - for the subsample of participants that had played an instrument - (iii) total hours of musical training (r = -0.12 in men and -0.10 in women). Ensemble playing added significant variance. Twin modelling showed that alexithymia had a moderate heritability of 36% and that the association with musical practice could be explained by shared genetic influences. Associations between musical training and alexithymia remained significant when controlling for education, depression, and intelligence. Musical achievement and musical practice are associated with lower levels of alexithymia in both men and women. Musical engagement thus appears to be associated with higher emotional competence, although effect sizes are small. The association between musical training and alexithymia appears to be entirely genetically mediated, suggesting genetic pleiotropy.


T-lymphocyte function after retroviral-mediated thymidine kinase gene transfer and G418 selection.
Generation of an efficient graft-versus-leukemia (GVL) effect in patients with hematological malignancies who relapse after allogeneic bone marrow transplantation depends in part upon the number of infused T lymphocytes. Currently, a GVL reaction cannot be achieved without inducing concomitant graft-versus-host disease (GVHD); thus, one strategy is to try to modulate this GVL/GVHD ratio. We engineered human T lymphocytes with herpes simplex virus-thymidine kinase and neomycin resistance genes, with an LXSN-derived vector that confers a ganciclovir-specific sensitivity to the transduced T cells. We analyzed proliferation, interleukin-2 production, alloreactivity in a mixed lymphocyte culture, and clonogenicity during the different stages of retroviral infection and G418 selection. Our results confirm that a sufficient number of transduced T lymphocytes can be obtained after selection for clinical studies. Their proliferative activity, alloresponsiveness, and ability to produce and respond to interleukin-2 were retained. Compared with control populations, their clonogenicity, as assessed by limiting dilution assays, was reduced after retroviral infection and G418 selection by 1.6 and 2.9 logs, respectively, with both viral supernatant incubation and coculture procedures. This study shows that infection and selection with the thymidine kinase-neomycin resistance gene retroviral vector significantly reduces the number of functional T lymphocytes. This finding should be taken into account when establishing the dose of T lymphocytes necessary to trigger a modulated GVL/GVHD effect.


Beta-endorphin-like immunoreactivity in the forebrain and pituitary of the teleost Clarias batrachus (Linn.).
The organization of beta-endorphin-like immunoreactivity in the olfactory system, forebrain, and pituitary of the teleost Clarias batrachus was investigated. Immunoreactivity was prominently seen in the sensory neurons and basal cells in the olfactory epithelium and in some cells in the periphery and center (granule cells) of the olfactory bulb. Immunoreactive fibers in the olfactory nerve enter the olfactory nerve layer of the olfactory bulb and branch profusely to form tufts organized as spherical neuropils in the glomerular layer. While fascicles of immunoreactive fibers were seen in the medial olfactory tracts, the lateral olfactory tracts showed individual immunoreactive fibers. Immunoreactive fibers in the medial olfactory tract extend into the telencephalon and form terminal fields in discrete telencephalic and preoptic areas; some immunoreactive fibers decussate in the anterior commissure, while others pass into the thalamus. While neurons of the nucleus lateralis tuberis revealed weak immunoreactivity, densely staining somata were seen at discrete sites along the wall of the third ventricle. Although a large population of immunoreactive cells was seen in the pars intermedia of the pituitary gland, few were seen in the rostral pars distalis and proximal pars distalis; immunoreactive fibers were seen throughout the pituitary gland.


Predictors of posttraumatic growth in 475 Chinese parents of children newly diagnosed with autism spectrum disorder.
To examine the predictive effects of children's symptom severity, rumination, parental self-efficacy, and social support on posttraumatic growth (PTG) in parents of autistic children. Parents (n = 475) completed the demographic questionnaire, Posttraumatic Growth Inventory, Autism Behavior Checklist, Event Related Rumination Inventory, Parenting Sense of Competence, and Social Support Rating Scale in a cross-sectional survey conducted in a tertiary hospital in Guangzhou, China, between September 2019 and January 2021. Multiple linear regression analyses were conducted using SPSS version 25.0. The PTG score was positively associated with rumination (r = 0.325, P < 0.05), parental self-efficacy (r = 0.219, P < 0.05), and social support (r = 0.374, P < 0.05). Multiple linear regression analysis revealed that household income (β = 0.095, P < 0.05), intrusive rumination (β = -0.100, P < 0.05), deliberate rumination (β = 0.391, P < 0.001), subjective support (β = 0.239, P < 0.001), and children's daily living skills deficiencies as perceived by parents (β = 0.107, P < 0.05) significantly predicted PTG, accounting for 33.3% of the variance [F(P) = 13.444, P < 0.001]. Psychosocial factors (rumination and subjective support) are essential to facilitate PTG in parents whose children are newly diagnosed with autism. With the consideration of different sociodemographic features, clinicians and researchers are encouraged to explore cognitive-based psychosocial interventions targeting parents' psychological growth and parenting training programs targeting autistic children's self-care ability.


Biohybrid neural interfaces: improving the biological integration of neural implants.
Implantable neural interfaces (NIs) have emerged in the clinic as outstanding tools for the management of a variety of neurological conditions caused by trauma or disease. However, the foreign body reaction triggered upon implantation remains one of the major challenges hindering the safety and longevity of NIs. The integration of tools and principles from biomaterial design and tissue engineering has been investigated as a promising strategy to develop NIs with enhanced functionality and performance. In this Feature Article, we highlight the main bioengineering approaches for the development of biohybrid NIs with an emphasis on relevant device design criteria. Technical and scientific challenges associated with the fabrication and functional assessment of technologies composed of both artificial and biological components are discussed. Lastly, we provide future perspectives related to engineering, regulatory, and neuroethical challenges to be addressed towards the realisation of the promise of biohybrid neurotechnology.


A review of initial data on pregnancy during the COVID-19 outbreak: implications for assisted reproductive treatments.
The current outbreak of the novel 2019 coronavirus disease (COVID-19) started in China in December 2019 and has since spread to several other countries. On March 25, 2020, a total of 375,498 cases had been confirmed globally with 2,201 cases in Brazil, showing the urgency of reacting to this international public health emergency. While in most cases, mild symptoms are observed, in some cases the infection leads to serious pulmonary disease. As a result, the possible consequences of the COVID-19 outbreak for pregnant women and its potential effects on the management of assisted reproductive treatments, demand attention. In this review, we summarize the latest research progress related to COVID-19 epidemiology and the reported data of pregnant women, and discuss the current evidence of COVID-19 infections during pregnancy and its potential consequences for assisted reproductive treatments. Reported data suggest that symptoms in pregnant women are similar to those in other people, and that there is no evidence for higher maternal or fetal risks. However, considering the initial data and lack of comprehensive knowledge on the pathogenesis of SARS-CoV-2 during pregnancy, human reproduction societies have recommended postponing the embryo transfers and do not initiate new treatment cycles. New evidence must be considered carefully in order to adjust these recommendations accordingly at any time and to guide assisted reproductive treatments.


The developing mammalian retina is partially protected from gentamicin toxicity.
Gentamicin retinal toxicity was tested in numerous studies on adult animal models, but not in the developing retina. Since differentiating cells and developing tissues may exhibit different degrees of sensitivity to toxic drugs, we aimed here to test the susceptibility of the developing mammalian retina to the toxic action of gentamicin. Gentamicin was injected in the right eye of newborn rabbits, aged 11-38 days. The left eye of each rabbit was injected with saline. Eight weeks after injection, electroretinographic (ERG) responses were recorded in the dark- and light-adapted states. The rabbits were then sacrificed, and the retinas were prepared for morphological examination and immunostaining for Glial Fibrillary Acidic Protein (GFAP) and Protein Kinase C (PKC). The ERG responses demonstrated practically no functional damage to the retina of rabbits injected at postnatal age of 11 and 13 days, and a gradually increasing severity of functional damage with increasing postnatal age of intravitreal gentamicin injection. The histopathological studies yielded similar results. GFAP immunoreactivity showed staining in Müller cells only in retinas that exhibited functional and structural damage. PKC immunoreactivity indicated lesser damage to the rod-bipolar cells compared to the photoreceptors. The ERG data and morphological observations suggest that processes involved in development of the rabbit retina, such as outer segment elongation may provide partial or even complete protection to the retina from toxic insults such as a single dose of gentamicin.


"My husband usually makes those decisions": gender, behavior, and attitudes toward the marine environment.
Human behavior impacts the environment we live in. In order to better understand how one group, boat owners, in three Nordic countries adjacent to the Baltic Sea; Sweden, Finland and Denmark, viewed the relationship between the marine environment, leisure boats and issues of responsibility, a survey study was conducted (n = 1701). The results show that there are differences between gender in many areas and those women in general are more environmentally friendly than men in their views and behavior. Men and women seek information about boating by different channels and this knowledge may be used in future information campaigns. Both men and women ranked boat owners as having the lowest impact on the marine environment and perceived these to be responsible for addressing environmental issues caused by leisure boat activities. The results also show that it is important to prove the effectiveness of an environmentally safe product since this factor is ranked higher than price when considering buying a product. The results suggest that once environmentally friendly behavior is established, such as recycling, this behavior continues. One implication of this study is that small changes in human behavior are seen as acceptable but larger commitments are more difficult to achieve. If individuals do not feel responsible for causing environmental damage, this aspect needs to be addressed in information aimed at this group. Novel approaches on framing the information and new ways of disseminating information are needed.


Faecal Metaproteomic Analysis Reveals a Personalized and Stable Functional Microbiome and Limited Effects of a Probiotic Intervention in Adults.
Recent metagenomic studies have demonstrated that the overall functional potential of the intestinal microbiome is rather conserved between healthy individuals. Here we assessed the biological processes undertaken in-vivo by microbes and the host in the intestinal tract by conducting a metaproteome analysis from a total of 48 faecal samples of 16 healthy adults participating in a placebo-controlled probiotic intervention trial. Half of the subjects received placebo and the other half consumed Lactobacillus rhamnosus GG for three weeks (1010 cfu per day). Faecal samples were collected just before and at the end of the consumption phase as well as after a three-week follow-up period, and were processed for microbial composition and metaproteome analysis. A common core of shared microbial protein functions could be identified in all subjects. Furthermore, we observed marked differences in expressed proteins between subjects that resulted in the definition of a stable and personalized microbiome both at the mass-spectrometry-based proteome level and the functional level based on the KEGG pathway analysis. No significant changes in the metaproteome were attributable to the probiotic intervention. A detailed taxonomic assignment of peptides and comparison to phylogenetic microarray data made it possible to evaluate the activity of the main phyla as well as key species, including Faecalibacterium prausnitzii. Several correlations were identified between human and bacterial proteins. Proteins of the human host accounted for approximately 14% of the identified metaproteome and displayed variations both between and within individuals. The individually different human intestinal proteomes point to personalized host-microbiota interactions. Our findings indicate that analysis of the intestinal metaproteome can complement gene-based analysis and contributes to a thorough understanding of the activities of the microbiome and the relevant pathways in health and disease.


Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions.
Previous studies have shown that modulation of the receptor-mediated cannabinoid system during neuroinflammation can produce potent neuroprotective and anti-inflammatory effects. However, in this context, little is known about how selective activation of the cannabinoid type-2 receptor (CB2R) affects the activated state of the brain endothelium and blood-brain barrier (BBB) function. Using human brain tissues and primary human brain microvascular endothelial cells (BMVECs), we demonstrate that the CB2R is highly upregulated during inflammatory insult. We then examined whether the CB2R agonists could attenuate inflammatory responses at the BBB using a mouse model of LPS-induced encephalitis and highly selective CB2R agonists. Visualization by intravital microscopy revealed that administration of JWH133 [(6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran] or a novel resorcinol-based compound, O-1966 (1-[4-(1,1-dimethyl-heptyl)-2,6-dimethoxy-phenyl]-3-methyl-cyclohexanol), greatly attenuated leukocyte adhesion in surface pial vessels and in deep ascending cortical postcapillary venules. BBB permeability assessments with small and large fluorescent tracers showed that CB2R agonists were effective at preventing barrier leakiness after LPS administration. To determine whether the effects by CB2R agonists on barrier protection are not only due to the CB2R modulation of immune cell function, we tested the agonists in vitro with barrier-forming primary BMVECs. Remarkably, the addition of CB2R agonist increased transendothelial electrical resistance and increased the amount of tight junction protein present in membrane fractions. Furthermore, CB2R agonists decreased the induction of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 surface expression in BMVECs exposed to various proinflammatory mediators. Together, these results suggest that pharmacological CB2R ligands offer a new strategy for BBB protection during neuroinflammation.


Functional bowel disorders and associated risk factors in hemodialysis patients in Turkey.
Functional bowel disorders (FBDs) impair the quality of life in patients with end-stage renal disease (ESRD). The aim of our study was to determine the prevalence and distribution of the subtypes of FBDs in hemodialysis (HD) patients. This prospective, cross-sectional study included 80 patients who received HD for more than 3 months (patient group) and 80 healthy controls (control group). FBDs were diagnosed according to the Rome II diagnostic criteria by excluding organic pathologies. Forty-six (57.5%) patients were males, and their average age was 62.13±12.92 (23-90) years. The mean duration of dialysis was 57.48±59.23 (3-312) months, and the mean Kt/V (K: dialyzer clearance of urea, t: dialysis time, V: volume of distrubition of urea) value was 1.53±0.31. The rate of FBDs was significantly higher in the patient group than in the control group (p=0.01). In total, 7.5% of the patients had irritable bowel syndrome, 3.8% had functional bloating, and 16.3% had functional constipation. FBDs were significantly higher in women (p=0.004). While there was no statistically significant difference between patients with and those without FBDs in terms of the presence of additional diseases, smoking, alcohol use, educational level, marital status, and resi- dential areas (p>0.05), serum phosphorus (P) levels were significantly higher in the patients with FBDs (p=0.03). FBDs and their functional constipation subtype are more common in HD patients than in the healthy population in Turkey. FBDs are most frequently observed in females and housewives with high serum P levels.


[State of antioxidant and oxygen transport system of the blood in the process of adaptation of the body to hypoxic hypoxia].
This article shows that in oxygen transported and antioxidative systems considerable changes take place during dynamic of adaptation to oxygen deficiency of inhaled air (every day 4 hours stay of animals in barochamber under pO2 7.45 kPa during 12 days). Single influence of hypoxic factor induced in erythrocytes peripheral blood increasing of haemoglobin affinity to oxygen, decreasing SOD and catalase activity on the background of increasing of malon aldehyde level. On 12-th day of adaptation of animals contents of TBA-active products in erythrocytes is saved on high level, activity of antioxidative enzymes is approached to original meanings, haemoglobin affinity to oxygen is decreased in comparison with control. Detected increasing content of creatine in erythrocytes during dynamic of rat adaptation to hypoxic hypoxia witnessed about erythropoiesis activation and quickened exit out of marrow young forms of erythrocytes.


School-based health centers: cost-benefit analysis and impact on health care disparities.
We evaluated the impact of school-based health centers-which provide essential health care for students by aiming to eliminate many access barriers-on health care access disparities and conducted a cost-benefit analysis. We employed a longitudinal quasi-experimental repeated-measures design. Primary data sources included the Ohio Medicaid claims, enrollment file with race/ethnicity, and survey reports from parents. We used hierarchical linear modeling to control unbalanced data because of student attrition. We assessed quarterly total Medicaid reimbursement costs for 5056 students in the SBHC and non-SBHC groups from 1997 to 2003. We calculated net social benefit to compare the cost of the SBHC programs with the value that SBHCs might save or create. With SBHCs, the gap of lower health care cost for African Americans was closed. The net social benefits of the SBHC program in 4 school districts were estimated as $1,352,087 over 3 years. We estimated that the SBHCs could have saved Medicaid about $35 per student per year. SBHCs are cost beneficial to both the Medicaid system and society, and may close health care disparity gaps.


Nutrition literacy is associated with income and place of residence but not with diet behavior and food security in the Palestinian society.
Palestinian society is going through health transition that is associated with increase in chronic diseases due to poor dietary habits so adequate integration of nutrition information is important. The aim of this study is to find the association between nutrition literacy and diet behavior among a group of Palestinian participants. A sample of 101 Palestinian participants were recruited to participate in the study. An online survey was used to collect study data. Newest Vital Sign quiz was used to collect information on nutrition literacy and Short Format of the Diet Health and Knowledge Survey (SFDHKS) was used to collect information on diet behavior and USDA food security questionnaire was used to collect data on food security. Data was analyzed utilizing SPSS 21. This study included 101 participants, mean age 22.7 y ± 8.7 y, mainly females (females were 83.2% and males were 16.8%). 5.7% of the study participants were obese, 13.8% overweight and 10.3% were underweight. The prevalence of adequate nutrition literacy was 29%. There was minimal association between diet behavior and nutrition literacy, food security and BMI categories, but significant association with income and living in city relative to village (p < 0.05). Only 11 participants had some form of food insecurity. There is low prevalence of adequate nutrition literacy. Nutrition literacy depends on social and economic aspects but further research is need to understand its relationship to diet behavior.


Positional cloning of Lps, and the general role of toll-like receptors in the innate immune response.
In mice (and by inference, in all mammals), a single pathway exists to serve lipopolysaccharide (LPS) signal transduction, and as such, allelic mutations at a single locus entirely abolish responses to LPS in C3H/HeJ and C57BL/10ScCr mice. Positional cloning of this locus, known as Lps, revealed that mutations of the Toll-like receptor 4 gene (Tlr4) are responsible for endotoxin resistance. A quick succession of studies have shown Tlr4 to be the critical transmembrane component of the LPS signal transduction complex. As LPS sensing by Tlr4 depends on physical contact between the two molecules, Tlr4 is a direct interface with the microbial world. Eight other molecules with strong similarity to Tlr4 are presently known in mammals, and taking Tlr4 as a model, all may be guessed to participate in the early detection of invasive pathogens. Acting together, the Toll-like receptors may be assumed to present macrophages with a comprehensive "picture" of the micobial world, and thus comprise the principal sensing molecules utilized by cells of the innate immune system.


Holographic subsonic flow visualization.
A pulsed ruby laser holographic interferometer was used to detect density gradients in the airflow around an airfoil at subsonic speeds in a low speed wind tunnel. These experiments proved that vibration of the optical components or object between exposures of the interferometric hologram does not destroy the detection of density gradients but actually can aid in the flow visualization. The density gradients determined from the fringe pattern analysis are consistent with the anticipated flow pattern.


Dystroglycan Mediates Clustering of Essential GABAergic Components in Cerebellar Purkinje Cells.
Muscle dystrophin-glycoprotein complex (DGC) links the intracellular cytoskeleton to the extracellular matrix. In neurons, dystroglycan and dystrophin, two major components of the DGC, localize in a subset of GABAergic synapses, where their function is unclear. Here we used mouse models to analyze the specific role of the DGC in the organization and function of inhibitory synapses. Loss of full-length dystrophin in mdx mice resulted in a selective depletion of the transmembrane β-dystroglycan isoform from inhibitory post-synaptic sites in cerebellar Purkinje cells. Remarkably, there were no differences in the synaptic distribution of the extracellular α-dystroglycan subunit, of GABAA receptors and neuroligin 2. In contrast, conditional deletion of the dystroglycan gene from Purkinje cells caused a disruption of the DGC and severely impaired post-synaptic clustering of neuroligin 2, GABAA receptors and scaffolding proteins. Accordingly, whole-cell patch-clamp analysis revealed a significant reduction in the frequency and amplitude of spontaneous IPSCs recorded from Purkinje cells. In the long-term, deletion of dystroglycan resulted in a significant decrease of GABAergic innervation of Purkinje cells and caused an impairment of motor learning functions. These results show that dystroglycan is an essential synaptic organizer at GABAergic synapses in Purkinje cells.


Morton's ranking of races by cranial capacity. Unconscious manipulation of data may be a scientific norm.
Samuel George Morton, self-styled objective empiricist, amassed the world's largest pre-Darwinian collection of human skulls. He measured their capacity and produced the results anticipated in an age when few Caucasians doubted their innate superiority: whites above Indians, blacks at the bottom. Morton published all his raw data, and it is shown here that his summary tables are based on a patchwork of apparently unconscious finagling. When his data are properly reinterpreted, all races have approximately equal capacities. Unconscious or dimly perceived finagling is probably endemic in science, since scientists are human beings rooted in cultural contexts, not automatons directed toward external truth.


Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity.
Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP), widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7), a Rho GDP/GTP exchange factor (Rho-GEF) localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7(KO)) have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments. We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7. These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus.


Supported Housing as a recovery option for long-stay patients with severe mental illness in a psychiatric hospital in South India: Learning from an innovative de-hospitalization process.
Individuals with severe mental illness have long been segregated from living in communities and participating in socio- cultural life. In recent years, owing to progressive legislations and declarations (in India and globally), there has been a growing movement towards promoting social inclusion and community participation, with emphasis on the need to develop alternative and inclusive care paradigms for persons with severe mental illness. However, transitions from inpatient care to community settings is a complex process involving implications at multiple levels involving diverse stakeholders such as mental health service users, care providers, local communities and policy makers. This article studies how the transition from a hospital setting to a community-based recovery model for personals with severe mental illness can be facilitated. It reflects on the innovative process of creating a Supported Housing model in South India, where 11 MH Service users transitioned from a psychiatric ECRC to independent living facilities. Experiences in various phases of the project development, including care provider- and community level responses and feedback were scrutinised to understand the strategies that were employed in enabling the transition. Qualitative methods (including in-depth interviews and naturalistic observations) were used with residents and staff members to explore the challenges they encountered in stabilizing the model, as well as the psychosocial benefits experienced by residents in the last phase. These were complemented with a Brief Psychiatric Rating Scale (BPRS) and WHO Quality of Life scale to compare baseline and post-assessment results and an increase of quality of life. Results display a significant reduction of psychiatric symptoms in patients (p< 0.5). It also describes the challenges encountered in the current context, and strategies that were used to respond and adapt the model to address these concerns effectively. Positive behavioural and psycho-emotional changes were observed amongst the residents, significant amongst those being enhanced in their mobility and participation. The article concludes by discussing the implications of this study for the development of innovative community-based models in wider contexts.


The role of heme in hemolysis-induced acute pancreatitis.
The aim was to reveal the mechanism of hemolysis-induced acute pancreatitis and to evaluate the role of heme and heme oxygenase activity in inducing pancreatic inflammation in an experimental hemolysis model. Hemolytic anemia was induced in rats by intraperitoneal injection of 60 mg/kg acetylphenylhydrazine (APH). To evaluate the toxic effect of free heme after hemolysis, heme oxygenase inhibitor (HOI) was used to inhibit the enzyme which decreases the free heme concentration after hemolysis. One hundred and fifty rats were divided into two treatment and three control groups. Rats in the hemolysis group were given APH intraperitoneally. Rats in the HOI+hemolysis group were given Cr(III)mesoporphyrin IX chloride as HOI and then APH intraperitoneally. Serum amylase and lipase levels as well as pancreatic tissue cytokine content were determined and histological examination performed. No hemolysis or pancreatitis was seen in the control groups. Massive hemolysis was seen in 22 of the 30 rats of the hemolysis group and 20 of the 30 rats of the HOI+hemolysis group. The total pancreatitis rates were 60% and 76.6% in the hemolysis and HOI+hemolysis groups, respectively (p<0.05). Pancreatic cytokine levels were significantly higher in the HOI+hemolysis and hemolysis groups than in all control groups. The highest ICAM-1 and MCP-1 levels were in the HOI+hemolysis group. Histological signs of acute pancreatitis were also more severe in this group. Acute massive hemolysis can induce acute pancreatitis. Excess of free vascular heme seems to be an inducer of inflammation by modulating ICAM-1 and MCP-1.


International outpatient parenteral antimicrobial therapy.
On an international basis, outpatient parenteral antimicrobial therapy (OPAT) varies greatly. There are cultural as well as economic issues which make it different in every country. In general, the duration of hospital stay varies with the outpatient resources available and the economic base for them. In some countries, there may not be money available for any intravenous antibiotics, even in the hospital. In addition, there are great differences in outpatient intravenous therapy, with infusion clinics proliferating in China, yet these are scarce in the UK. There is also considerable variation in the use of intramuscular compared with intravenous therapies. In Italy, intramuscular ceftriaxone is used more often than intravenous therapy. While ceftriaxone use is high in the US, its use is surpassed on a per capita basis by Italy, and it is most interesting that the rate of antimicrobial resistance is lower in Italy than in most other European countries. Whether this relates to outpatient use, parenteral use or other unknown factors is unclear. Obviously, further studies are necessary.


Prognostic Factors of Surgically Treated Early-Stage Small Cell Neuroendocrine Carcinoma of the Cervix.
Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare malignancy and has a high mortality despite of aggressive surgical treatment. The aims of this study were to determine the prognostic factors associated with the survival of surgically treated patients with early-stage SCNECC and to see whether carboplatin plus paclitaxel (TC) therapy after surgery can improve their survival. Thirty-eight women with FIGO stages IA2 (n = 1), IB1 (n = 31), IB2 (n = 3), and IIA1 (n = 3) were treated with radical hysterectomy, followed by adjuvant TC or non-TC, with or without radiotherapy, in our hospital between 2004 and 2013. Medical charts and clinical data were retrieved and retrospectively reviewed. The Kaplan-Meier method and Cox regression model were used for survival analysis. The mean age of patients were 40.4 ± 7.0 years. The preoperative detection rate of SCNECC was only 34.2%. The overall 1-, 2-, and 5-year survival rate was 81.6%, 54.7%, and 43%, respectively, whereas the 1-, 2-, and 5-year cumulative recurrence rate was 37.8%, 44.2%, and 49.3%, respectively. For overall survival (OS), the univariate survival analysis indicated that tumor homology, parametrial invasion, chemotherapy regimens, and chemotherapy courses were risk factors. For disease-free survival, the univariate survival analysis identified lymph node involvement, tumor homology, parametrial invasion, chemotherapy regimens, and chemotherapy courses as risk factors. However, when multivariable Cox regression model was used, only parametrial invasion and postoperative chemotherapy regimen were identified as risk factors for both OS (P = 0.037 and P = 0.016) and disease-free survival (P = 0.044 and P = 0.018). Small cell neuroendocrine carcinoma of the cervix is a deadly variant of cervical cancer. Postoperative TC chemotherapy may improve the OS and disease-free survival in women with early-stage SCNECC.


Sex-Specific Biology of the Human Malaria Parasite Revealed from the Proteomes of Mature Male and Female Gametocytes.
The gametocytes of the malaria parasites are obligate for perpetuating the parasite's life cycle through mosquitoes, but the sex-specific biology of gametocytes is poorly understood. We generated a transgenic line in the human malaria parasite Plasmodium falciparum, which allowed us to accurately separate male and female gametocytes by flow cytometry. In-depth analysis of the proteomes by liquid chromatography-tandem mass spectrometry identified 1244 and 1387 proteins in mature male and female gametocytes, respectively. GFP-tagging of nine selected proteins confirmed their sex-partitions to be agreeable with the results from the proteomic analysis. The sex-specific proteomes showed significant differences that are consistent with the divergent functions of the two sexes. Although the male-specific proteome (119 proteins) is enriched in proteins associated with the flagella and genome replication, the female-specific proteome (262 proteins) is more abundant in proteins involved in metabolism, translation and organellar functions. Compared with the Plasmodium berghei sex-specific proteomes, this study revealed both extensive conservation and considerable divergence between these two species, which reflect the disparities between the two species in proteins involved in cytoskeleton, lipid metabolism and protein degradation. Comparison with three sex-specific proteomes allowed us to obtain high-confidence lists of 73 and 89 core male- and female-specific/biased proteins conserved in Plasmodium The identification of sex-specific/biased proteomes in Plasmodium lays a solid foundation for understanding the molecular mechanisms underlying the unique sex-specific biology in this early-branching eukaryote.


The deltaC isoform of CaMKII is activated in cardiac hypertrophy and induces dilated cardiomyopathy and heart failure.
Recent studies have demonstrated that transgenic (TG) expression of either Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) or CaMKIIdeltaB, both of which localize to the nucleus, induces cardiac hypertrophy. However, CaMKIV is not present in heart, and cardiomyocytes express not only the nuclear CaMKIIdeltaB but also a cytoplasmic isoform, CaMKIIdeltaC. In the present study, we demonstrate that expression of the deltaC isoform of CaMKII is selectively increased and its phosphorylation elevated as early as 2 days and continuously for up to 7 days after pressure overload. To determine whether enhanced activity of this cytoplasmic deltaC isoform of CaMKII can lead to phosphorylation of Ca2+ regulatory proteins and induce hypertrophy, we generated TG mice that expressed the deltaC isoform of CaMKII. Immunocytochemical staining demonstrated that the expressed transgene is confined to the cytoplasm of cardiomyocytes isolated from these mice. These mice develop a dilated cardiomyopathy with up to a 65% decrease in fractional shortening and die prematurely. Isolated myocytes are enlarged and exhibit reduced contractility and altered Ca2+ handling. Phosphorylation of the ryanodine receptor (RyR) at a CaMKII site is increased even before development of heart failure, and CaMKII is found associated with the RyR in immunoprecipitates from the CaMKII TG mice. Phosphorylation of phospholamban is also increased specifically at the CaMKII but not at the PKA phosphorylation site. These findings are the first to demonstrate that CaMKIIdeltaC can mediate phosphorylation of Ca2+ regulatory proteins in vivo and provide evidence for the involvement of CaMKIIdeltaC activation in the pathogenesis of dilated cardiomyopathy and heart failure.


Re-prioritizing traffic stops to reduce motor vehicle crash outcomes and racial disparities.
Law enforcement traffic stops are one of the most common entryways to the US justice system. Conventional frameworks suggest traffic stops promote public safety by reducing dangerous driving practices and non-vehicular crime. Law enforcement agencies have wide latitude in enforcement, including prioritization of stop types: (1) safety (e.g. moving violation) stops, (2) investigatory stops, or (3) economic (regulatory and equipment) stops. In order to prevent traffic crash fatalities and reduce racial disparities, the police department of Fayetteville, North Carolina significantly re-prioritized safety stops. Annual traffic stop, motor vehicle crash, and crime data from 2002 to 2016 were combined to examine intervention (2013-2016) effects. Fayetteville was compared against synthetic control agencies built from 8 similar North Carolina agencies by weighted matching on pre-intervention period trends and comparison against post-intervention trends. On average over the intervention period as compared to synthetic controls, Fayetteville increased both the number of safety stops + 121% (95% confidence interval + 17%, + 318%) and the relative proportion of safety stops (+ 47%). Traffic crash and injury outcomes were reduced, including traffic fatalities - 28% (- 64%, + 43%), injurious crashes - 23% (- 49%, + 16%), and total crashes - 13% (- 48%, + 21%). Disparity measures were reduced, including Black percent of traffic stops - 7% (- 9%, - 5%) and Black vs. White traffic stop rate ratio - 21% (- 29%, - 13%). In contrast to the Ferguson Effect hypothesis, the relative de-prioritization of investigatory stops was not associated with an increase in non-traffic crime outcomes, which were reduced or unchanged, including index crimes - 10% (- 25%, + 8%) and violent crimes - 2% (- 33%, + 43%). Confidence intervals were estimated using a different technique and, given small samples, may be asymmetrical. The re-prioritization of traffic stop types by law enforcement agencies may have positive public health consequences both for motor vehicle injury and racial disparity outcomes while having little impact on non-traffic crime.


Deterministic signal associated with a random field.
Stochastic fields do not generally possess a Fourier transform. This makes the second-order statistics calculation very difficult, as it requires solving a fourth-order stochastic wave equation. This problem was alleviated by Wolf who introduced the coherent mode decomposition and, as a result, space-frequency statistics propagation of wide-sense stationary fields. In this paper we show that if, in addition to wide-sense stationarity, the fields are also wide-sense statistically homogeneous, then monochromatic plane waves can be used as an eigenfunction basis for the cross spectral density. Furthermore, the eigenvalue associated with a plane wave, exp[i(k · r-ωt)], is given by the spatiotemporal power spectrum evaluated at the frequency (k, ω). We show that the second-order statistics of these fields is fully described by the spatiotemporal power spectrum, a real, positive function. Thus, the second-order statistics can be efficiently propagated in the wavevector-frequency representation using a new framework of deterministic signals associated with random fields. Analogous to the complex analytic signal representation of a field, the deterministic signal is a mathematical construct meant to simplify calculations. Specifically, the deterministic signal associated with a random field is defined such that it has the identical autocorrelation as the actual random field. Calculations for propagating spatial and temporal correlations are simplified greatly because one only needs to solve a deterministic wave equation of second order. We illustrate the power of the wavevector-frequency representation with calculations of spatial coherence in the far zone of an incoherent source, as well as coherence effects induced by biological tissues.


How representative is the 'Representative Value' of refraction provided by the Shin-Nippon NVision-K 5001 autorefractor?
The aim of the study was to evaluate the level of agreement between the 'Representative Value' (RV) of refraction obtained from the Shin-Nippon NVision-K 5001 instrument with values calculated from individual measurement readings using standard algebraic methods. Cycloplegic autorefraction readings for 101 myopic children aged 8-13 years (10.9 ± 1.42 years) were obtained using the Shin-Nippon NVision-K 5001. Ten autorefractor measurements were taken for each eye. The spherical equivalent (SE), sphere (Sph) and cylindrical component (Cyl) power of each eye were calculated, firstly, by averaging the 10 repeated measurements (Mean SE, Mean Sph and Mean Cyl), and secondly, by the vector representation method (Vector SE, Vector Sph and Vector Cyl). These calculated values were then compared with those of RV (RV SE, RV Sph and RV Cyl) provided by the proprietary software of the NVision-K 5001 using one-way analysis of variance (anova). The agreement between the methods was also assessed. The SE of the subjects ranged from -5.37 to -0.62 D (mean ± SD, = -2.89 ± 1.01 D). The Mean SE was in exact agreement with the Vector SE. There were no significant differences between the RV readings and those calculated using non-vectorial or vectorial methods for any of the refractive powers (SE, p = 0.99; Sph, p = 0.93; Cyl, p = 0.24). The (mean ± SD) differences were: RV SE vs Mean SE (and also RV SE vs Vector SE) -0.01 ± 0.06 D; RV Sph vs Mean Sph, -0.01 ± 0.05 D; RV Sph vs Vector Sph, -0.04 ± 0.06 D; RV Cyl vs Mean Cyl, 0.01 ± 0.07 D; RV Cyl vs Vector Cyl, 0.06 ± 0.09 D. Ninety-eight percent of RV reading differed from their non-vectorial or vectorial counterparts by less than 0.25 D. The RV values showed good agreement to the results calculated using conventional methods. Although the formula used to calculate RV by the NVision-K 5001 autorefractor is proprietary, our results provide validation for the use of RV measurements in clinical practice and vision science research.


Demonstration of motor imagery movement and phantom movement-related neuronal activity in human thalamus.
Functional imaging studies show that motor imagery activates multiple structures in the human forebrain. We now show that phantom movements in an amputee and imagined movements in intact individuals elicit responses from neurons in several human thalamic nuclei. These include the somatic sensory nucleus receiving input from the periphery (ventral caudal), and the motor nuclei receiving input from the cerebellum [ventral intermediate (Vim)] and the basal ganglia [ventral oral posterior (Vop)]. Seven neurons in the amputee showed phantom movement-related activity (three Vim, two Vop, and two ventral caudal). In addition, seven neurons in a group of three controls showed motor imagery-related activity (four Vim and three Vop). These studies were performed during single neuron recording sessions in patients undergoing therapeutic treatment of phantom pain, tremor, and chronic pain conditions by thalamic stimulation. The activity of neurons in these sensory and motor nuclei, respectively, may encode the expected sensory consequences and the dynamics of planned movements.


MicroRNAs as biomarkers and treatment targets in status epilepticus.
Microribonucleic acids (miRNAs) are short noncoding ribonucleic acids (RNAs) that have been proposed as potential biomarkers for epilepsy, acute seizures, and status epilepticus. Various properties support their potential in this regard, including relative stability and amenability to rapid quantitation in biofluids. Several miRNAs are enriched in the brain and within specific cell types. Dysregulation of miRNAs has been reported in brain regions damaged by status epilepticus and in resected brain tissue from patients with drug-resistant epilepsy. Silencing miRNAs using antisense-like oligonucleotides termed antagomirs has been reported to suppress evoked and spontaneous seizures in animal models, indicating therapeutic applications. The prospect of miRNAs as mechanistic biomarkers is supported by recent studies showing blood levels of brain-enriched miRNAs increase after status epilepticus in rodents, and clinical studies have identified miRNAs upregulated in human cerebrospinal fluid after status epilepticus. It remains unproven, however, whether there are miRNAs that uniquely identify acute seizures, chronic epilepsy, or the process of epileptogenesis. Finally, efforts have turned to the challenge of proving that some of the circulating miRNAs actually originate from the brain. New models that feature a biochemically-labeled protein involved in miRNA function and restricted to specific brain cell types offer opportunities to resolve this issue. This review summarizes recent progress on miRNAs as diagnostic biomarkers of status epilepticus and considers some of the unanswered questions and future directions. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.


Recent progress in chiral separation principles in capillary electrophoresis.
This review summarizes recent developments in the field of chiral separations by electromigration techniques including capillary zone electrophoresis (CZE), capillary gel electrophoresis (CGE), isotachophoresis (ITP), electrokinetic chromatography (EKC), and capillary electrochromatography (CEC). This overview focuses on the development of new chiral selectors and the introduction of new techniques rather than applications of already established selectors and methods. The mechanisms of the different chiral separation principles are discussed.


Evaluating benign breast disease.
Benign breast diseases are present in some form in nearly all women. A basic understanding of breast anatomy and physiology, underlying pathology and methods available for evaluating breast problems provides the ability to assess the client's breast complaint. Four common breast problems--fibrocystic disease, fibroadenoma, mammary duct ectasia, and intraductal papilloma--are described along with guidelines for assessment and referral or follow-up. Current breast-imaging options are discussed in terms of their usefulness and limitations. The value of consumer education regarding benign breast problems cannot be overstated. The National Cancer Institute offers free consumer information explaining benign breast diseases and evaluation techniques.


Optics and electron optics as competitive and complementary technologies in electronics.
Optics and electron optics have played a competitive and a complementary role in communications. While the replacement of the light beam by the electron beam ushered in modern television, the advent of the laser and the technology which has accompanied its development have made light optics competitive in areas which, for a while, appeared reserved to purely electronic devices. Computer memories and micromachining and welding are better examples of this than are television displays. Electron optics has an unchallenged monopoly only where the density of information to be recorded or read out exceeds substantially an element for a unit of length equal to a wavelength of light. The competition of optics and electron optics is, however, more than outbalanced by their complementary roles. This may be illustrated from all phases of television practice and is accentuated in some of the more recent developments.


Protective Effect of Alprostadil on Acute Pancreatitis in Rats via Inhibiting Janus Kinase 2 (JAK2)/STAT3 Signal Transduction Pathway.
BACKGROUND Alprostadil can inhibit inflammation and reduce inflammation-related injury in many inflammatory diseases. However, the anti-inflammatory effect of alprostadil in decreasing acute pancreatitis (AP) injury remains unknow. This study aimed to investigate the possible protective effects and mechanism of alprostadil against AP in rats. MATERIAL AND METHODS Forty healthy Sprague‑Dawley rats were randomly divided into a control group, an AP group, an AP-alprostadil group, an AP-AG490 group, and an AP-(alprostadil+AG490) group. An animal model of acute pancreatitis was established. The pathological changes of the pancreases in each group were observed. We assessed levels of malondialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO), as well as serum IL-1ß, IL-6, IL-10, and TNF-alpha. TUNEL assay was used to detect apoptosis of pancreatic cells. The proteins p-Jak2 and p-Stat3 were investigated by Western blot. RESULTS Compared with the control group, pancreatic pathological score, pancreatic apoptosis, MDA, MPO, serum IL-1ß, IL-6, and TNF-alpha levels were significantly higher in the AP group, and SOD levels were significantly decreased. Compared with the AP group, after treatment with alprostadil, AG490, and alprostadil+AG490, respectively, the pancreatic pathological score, apoptosis, MDA, MPO, serum IL-1ß, IL-6, and TNF-alpha were significantly decreased in AP rats, while SOD levels were significantly increased. The protein levels of p-JAK2 and p-STAT3 were significantly upregulated in the AP group compared with the control group, and the protein levels of p-JAK2 and p-STAT3 after treatment with alprostadil, AG490, and alprostadil+AG490 were significantly decreased, and the effect of alprostadil+AG490 was the strongest. CONCLUSIONS Alprostadil can reduce pancreatic tissue damage, delay pancreatic cell apoptosis, and reduce inflammation and anti-oxidative stress by inhibiting the JAK2/STAT3 signal pathway, thus protecting the pancreas.


Functional Characterization of MdTAC1a Gene Related to Branch Angle in Apple (Malus x domestica Borkh.).
The Tiller Angle Control 1 (TAC1) gene belongs to the IGT family, which mainly controls plant branch angle, thereby affecting plant form. Two members of MdTAC1 are identified in apple; the regulation of apple branch angle by MdTAC1 is still unclear. In this study, a subcellular localization analysis detected MdTAC1a in the nucleus and cell membrane, but MdTAC1b was detected in the cell membrane. Transgenic tobacco by overexpression of MdTAC1a or MdTAC1b showed enlarged leaf angles, the upregulation of several genes, such as GA 2-oxidase (GA2ox), and a sensitive response to light and gravity. According to a qRT-PCR analysis, MdTAC1a and MdTAC1b were strongly expressed in shoot tips and vegetative buds of weeping cultivars but were weakly expressed in columnar cultivars. In the MdTAC1a promoter, there were losses of 2 bp in spur cultivars and 6 bp in weeping cultivar compared with standard and columnar cultivars. An InDel marker specific to the MdTAC1a promoter was developed to distinguish apple cultivars and F1 progeny. We identified a protein, MdSRC2, that interacts with MdTAC1a, whose encoding gene which was highly expressed in trees with large branch angles. Our results indicate that differences in the MdTAC1a promoter are major contributors to branch-angle variation in apple, and the MdTAC1a interacts with MdSRC2 to affect this trait.


Real-Time Monitoring of ATP-Responsive Drug Release Using Mesoporous-Silica-Coated Multicolor Upconversion Nanoparticles.
Stimuli-responsive drug delivery vehicles have garnered immense interest in recent years due to unparalleled progress made in material science and nanomedicine. However, the development of stimuli-responsive devices with integrated real-time monitoring capabilities is still in its nascent stage because of the limitations of imaging modalities. In this paper, we describe the development of a polypeptide-wrapped mesoporous-silica-coated multicolor upconversion nanoparticle (UCNP@MSN) as an adenosine triphosphate (ATP)-responsive drug delivery system (DDS) for long-term tracking and real-time monitoring of drug release. Our UCNP@MSN with multiple emission peaks in UV-NIR wavelength range was functionalized with zinc-dipicolylamine analogue (TDPA-Zn(2+)) on its exterior surface and loaded with small-molecule drugs like chemotherapeutics in interior mesopores. The drugs remained entrapped within the UCNP-MSNs when the nanoparticles were wrapped with a compact branched polypeptide, poly(Asp-Lys)-b-Asp, because of multivalent interactions between Asp moieties present in the polypeptide and the TDPA-Zn(2+) complex present on the surface of UCNP-MSNs. This led to luminescence resonance energy transfer (LRET) from the UCNPs to the entrapped drugs, which typically have absorption in UV-visible range, ultimately resulting in quenching of UCNP emission in UV-visible range while retaining their strong NIR emission. Addition of ATP led to a competitive displacement of the surface bound polypeptide by ATP due to its higher affinity to TDPA-Zn(2+), which led to the release of the entrapped drugs and subsequent elimination of LRET. Monitoring of such ATP-triggered ratiometric changes in LRET allowed us to monitor the release of the entrapped drugs in real-time. Given these results, we envision that our proposed UCNP@MSN-polypeptide hybrid nanoparticle has great potential for stimuli-responsive drug delivery as well as for monitoring biochemical changes taking place in live cancer and stem cells.


Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients.
Valganciclovir (Valcyte) has recently been approved for the prevention of cytomegalovirus (CMV) disease in high-risk (CMV donor positive [D+]/recipient negative [R-]) solid organ transplant (SOT) recipients. Large-scale studies describing the pharmacokinetics of valganciclovir in SOT recipients are lacking. A recent randomised, double-blind study of valganciclovir in 364 D+/R- (intent-to-treat population) SOT recipients provided valuable data on which a population pharmacokinetic analysis was performed. The pharmacokinetics of ganciclovir from oral ganciclovir (Cymevene, 1000 mg three times daily) and from valganciclovir (900 mg once daily) were described with plasma levels from 240 patients (1181 datapoints describing 449 pharmacokinetic profiles) using nonlinear mixed-effects modelling (NONMEM) software. A two-compartment pharmacokinetic model with separate absorption/metabolism and absorption parameters for valganciclovir and ganciclovir, respectively, was developed. Exposure to ganciclovir from valganciclovir averaged 1.65-fold greater than that from oral ganciclovir (95% CI 1.58, 1.81); respective daily area under the plasma concentration-time curve values were 46.3 +/- 15.2 microg . h/mL and 28.0 +/- 10.9 microg . h/mL. The relative systemic exposure of ganciclovir was approximately 8-fold higher from valganciclovir than oral ganciclovir. Exposure to ganciclovir from valganciclovir was similar among liver, heart and kidney transplant recipients (46.0 +/- 16.1, 40.2 +/- 11.8 and 48.2 +/- 14.6 microg . h/ mL, respectively). Adherence to the prescribed dosing regimens, which were reduced for renal impairment, gave consistent exposure to ganciclovir. Oral valganciclovir produces exposures of ganciclovir exceeding those attained with oral ganciclovir, but in line with those reported after standard intravenous administration of ganciclovir. This indicates that oral valganciclovir is suitable in circumstances requiring prophylactic use of ganciclovir and allows for more convenient management of patients at risk of CMV disease.


Defect of zinc transporter ZRT1 ameliorates cadmium induced lipid accumulation in Saccharomyces cerevisiae.
Cadmium (Cd) is a non-essential divalent heavy metal that enters the cells by utilizing the transport pathways of the essential metals, like zinc (Zn), in Saccharomyces cerevisiae. This work focuses on Cd accumulation and its impact on deletion of Zn transporters Zrt1p and Zrt2p and lipid homeostasis. Cd exposure reduces the Zn levels in the mutant strains, and the effect was higher in zrt2Δ cells. Upon Cd exposure, the wild-type and zrt2Δ cells follow a similar pattern, but an opposite pattern was observed in zrt1Δ cells. The Cd influx and ROS levels were high in both wild-type cells and zrt2Δ cells but significantly reduced in zrt1Δ cells. Cd exposure led to accumulation of triacylglycerol and lipid droplets in wild-type cells and zrt2Δ cells but these levels were decreased in zrt1Δ cells. Hence, these studies suggest that the zrt1Δ cells provide resistance towards Cd and aid in the maintenance of lipid homeostasis in yeast cells.


[Peptide composition of extracts of cryopreserved pigs' and piglets' heart fragments].
It is known that extracts of cryopreserved organ fragments of pigs and piglets stimulate the processes of reparative regeneration. Therefore, the study of the extracts is essential for understanding the mechanism of their biological effects. In this paper was studied the molecular mass distribution of peptides in the extracts of cryopreserved heart fragments of pigs' and piglets', i.e., the chromatograms of pigs' heart extracts show 3 picks, whilst piglets' heart extract show 6 picks. The peculiarity of pigs' heart extracts is the absence of peptides with molecular mass of 10,000 and more. The differences in the intensity of extracts fluorescence prove that the peptides in pigs' heart extracts contain greater amount of tryptophan residues accessible for solvent. The synchronous fluorescence spectra of extracts were obtained which allows the identification of extract without assessment of their components. Results shown in this research could be used for control and standardization of heart extracts peptide composition under investigation of their biological quality.


Predicting natural language descriptions of mono-molecular odorants.
There has been recent progress in predicting whether common verbal descriptors such as "fishy", "floral" or "fruity" apply to the smell of odorous molecules. However, accurate predictions have been achieved only for a small number of descriptors. Here, we show that applying natural-language semantic representations on a small set of general olfactory perceptual descriptors allows for the accurate inference of perceptual ratings for mono-molecular odorants over a large and potentially arbitrary set of descriptors. This is noteworthy given that the prevailing view is that humans' capacity to identify or characterize odors by name is poor. We successfully apply our semantics-based approach to predict perceptual ratings with an accuracy higher than 0.5 for up to 70 olfactory perceptual descriptors, a ten-fold increase in the number of descriptors from previous attempts. These results imply that the semantic distance between descriptors defines the equivalent of an odorwheel.


Distribution and heterogeneity of mast cells in female reproductive tract and ovary on different days of the oestrus cycle in Angora goats.
The physiological distribution of mast cells (MCs) in the reproductive tract and ovary of 12 Angora goats was determined using light microscopic histochemical techniques. Uterus (corpus uteri and cornu uteri), uterine cervix, uterine tubes (isthmus and ampulla) and ovary samples were obtained by laparatomy from groups of animals during metoestrus, dioestrus and proestrus (days 5, 10 and 16 of the oestrous cycle). Tissues were fixed in Mota's fixative (basic lead acetate) for 48 h and embedded in paraffin. Six-micrometre-thick sections were stained with toluidine blue in 1% aqueous solution at pH 1.0 for 5 min and alcian blue-Safranin at pH 1.0 for 30 min. MCs were generally associated with blood vessels in all reproductive organs. In the uterus, they were concentrated mainly in the close of the uterine gland and deep stroma in the endometrium. Higher MC numbers were observed by toluidine blue staining in the uterus, uterine cervix and uterine tubes on days 10 (corpus uterine: 4.7 +/- 3.8 and cornu uterine: 4.9 +/- 3.5) and 16 (corpus uterine: 5.9 +/- 4.5 and cornu uterine: 5.4 +/- 2.4) of the oestrous cycle compared with day 5 (p < 0.05). Mast cells were not observed in the follicles, the corpus luteum and the underside of the surface epithelium of the ovarian cortex, but were observed in the interstitial cortical stroma and the ovarian medulla. In the ovary, MC numbers were significantly higher on day 16 of the oestrous cycle (cortex: 3.4 +/- 2.4 and medulla: 5.7 +/- 4.5, p < 0.05). Safranin-positive connective tissue MCs were not observed in the uterine tube on any occasion. These results indicate oestrous cycle-related changes in the number and location of MCs in goat reproductive organs.


Antiretroviral treatment start-time during primary SIV(mac) infection in macaques exerts a different impact on early viral replication and dissemination.
The time of infection is rarely known in human cases; thus, the effects of delaying the initiation of antiretroviral therapy (ART) on the peripheral viral load and the establishment of viral reservoirs are poorly understood. Six groups of macaques, infected intravenously with SIV(mac251), were given placebo or antiretroviral therapy to explore reservoir establishment; macaques were treated for 2 weeks, with treatment starting 4 hours, 7 or 14 days after infection. Viral replication and dissemination were measured in the gut (rectum), in the lung and in blood and lymphoid tissues (peripheral lymph nodes), by quantifying viral RNA, DNA and 2LTR circles. We used immunohistochemistry (CD4 and CD68) to assess the impact of these treatments on the relative amount of virus target cells in tissue. Treatment that was started 4 hours post-infection (pi) decreased viral replication and dissemination in blood and tissue samples, which were assessed on day 14 (RNA/DNA/2LTR circles). The virus remained detectable and lymphoid tissues were activated in LN and the gut in both placebo- and ART-treated animals. Viral RNA in plasma continued to be lower in macaques treated seven days after infection; however, this was not the case for viral DNA in peripheral blood mononuclear cells. There was a small but significant difference in RNA and DNA levels in tissues between placebo- and ART-treated animals on day 21. When started 14 days after infection, treatment resulted in a limited decrease in the plasma viral load. Treatment that was started 4 hours after infection significantly reduced viral replication and dissemination. When started 7 days after infection, it was of slight virological benefit in peripheral blood and in tissues, and treatment was even less effective if started 14 days pi. These data favor starting ART no longer than one week after intravenous SIV(mac251) exposure.


Transactional sex among youths in post-conflict Liberia.
This paper presents findings on sexual risk behaviours of Liberian youths based on five focus-group discussions conducted with 6th and 7th graders (n = 36) attending an elementary/middle school in Monrovia, Liberia. The purpose of the focus-group discussions was to gain an understanding of the sexual behaviours of in-school Liberian adolescents. The focus-group discussions were part of a larger study to adapt an evidence-based HIV-prevention intervention-Making Proud Choices!-for in-school youths. Post-conflict conditions were discussed as a contributor to the emergence of high-risk sexual behaviours, including transactional sex, sexual violence, and lack of condom-use. Transactional sex was often described by the focus-group participants as occurring between young females and older, more financially-secure males to obtain cash, food, clothing, western commodities, and school-fees and was often encouraged by parents and promoted by peers. The findings also indicate that female adolescents make choices to engage in transactional sex to gain access to a continuum of material and consumer needs. These findings suggest that individual risk-taking behaviours are nested within complex sexual economies and that HIV-prevention interventions should be considered that leverage females' agency and control.


Assessing symptom distress in cancer patients: the M.D. Anderson Symptom Inventory.
The purpose of this project was to develop the M. D. Anderson Symptom Inventory (MDASI), a brief measure of the severity and impact of cancer-related symptoms. A list of symptoms was generated from symptom inventories and by panels of clinicians. Twenty-six symptoms and 6 interference items were rated by a validation sample of 527 outpatients, a sample of 30 inpatients from the blood and bone marrow transplantation service, and a cross-validation sample of 113 outpatients. Clinical judgment and statistical techniques were used to reduce the number of symptoms. Reliability, validity, and sensitivity of the MDASI were examined. Cluster analysis, best subset analysis, and clinical judgment reduced the number of symptoms to a "core" list of 13 that accounted for 64% of the variance in symptom distress. Factor analysis demonstrated a similar pattern in both outpatient samples, and two symptom factors and the interference scale were reliable. Expected differences in symptom pattern and severity were found between patients with "good" versus "poor" performance status and between patients in active therapy and patients who were seen for follow-up. Patients rated fatigue-related symptoms as the most severe. Groups of patients classified by disease or treatment had severe symptoms that were not on the "core" list. The core items of the MDASI accounted for the majority of symptom distress reported by cancer patients in active treatment and those who were followed after treatment. The MDASI should prove useful for symptom surveys, clinical trials, and patient monitoring, and its format should allow Internet or telephone administration.


Expression and localization of alpha-tubulin N-acetyltransferase 1 in the reproductive system of male mice.
The structure of microtubules is essential for the fertilizing ability of spermatozoa. Acetylation of α-tubulin plays an important role in flagellar elongation and spermatozoa motility. Previous reports have suggested that alpha-tubulin N-acetyltransferase 1 (ATAT1) is the main acetyltransferase involved in the acetylation of α-tubulin. Although ATAT1 is reported to express in the testis, no information is available regarding its expression in elongated spermatids, epididymis, and mature spermatozoa. Hence, it remains unclear whether ATAT1 is involved in spermatozoa maturation and capacitation. Therefore, we evaluated the expression of ATAT1 in the mouse male reproductive system using immunostaining and western blotting. Our results showed that ATAT1 was expressed in spermatids during spermiogenesis in mouse testes, but its expression varied according to the seminiferous tubule stage. We observed ATAT1 in the cytoplasm of round spermatids, the flagella of elongated spermatids, and in the cytoplasm of step 16 spermatids, just before its release into the lumen. In addition, ATAT1 was expressed in epithelial cells of the epididymis. In spermatozoa of the cauda epididymis, ATAT1 expression was primarily observed in the midpiece of the spermatozoa. The localization of ATAT1 protein in the male germline was observed during spermiogenesis as well as during spermatozoa maturation. Our results suggest that ATAT1 may be involved in the formation of flagella and in the acetylation process, which has attracted attention in recent years regarding male infertility.


CRISPRs for Optimal Targeting: Delivery of CRISPR Components as DNA, RNA, and Protein into Cultured Cells and Single-Cell Embryos.
The rapid development of CRISPR technology greatly impacts the field of genetic engineering. The simplicity in design and generation of highly efficient CRISPR reagents allows more and more researchers to take on genome editing in different model systems in their own labs, even for those who found it daunting before. An active CRISPR complex contains a protein component (Cas9) and an RNA component (small guide RNA [sgRNA]), which can be delivered into cells in various formats. Cas9 can be introduced as a DNA expression plasmid, in vitro transcripts, or as a recombinant protein bound to the RNA portion in a ribonucleoprotein particle (RNP), whereas the sgRNA can be delivered either expressed as a DNA plasmid or as an in vitro transcript. Here we compared the different delivery methods in cultured cell lines as well as mouse and rat single-cell embryos and view the RNPs as the most convenient and efficient to use. We also report the detection of limited off-targeting in cells and embryos and discuss approaches to lower that chance. We hope that researchers new to CRISPR find our results helpful to their adaptation of the technology for optimal gene editing.


Genetic findings in Czech patients with limb girdle muscular dystrophy.
Limb girdle muscular dystrophies (LGMD) are a genetically heterogeneous group of muscular dystrophies. The study presents an overview of molecular characteristics of a large cohort of LGMD patients who are representative of the Czech LGMD population. We present 226 LGMD probands in which 433 mutant alleles carrying 157 different variants with a supposed pathogenic effect were identified. Fifty-four variants have been described only in the Czech LGMD population so far. LGMD R1 caplain3-related is the most frequent subtype of LGMD involving 53.1% of patients with genetically confirmed LGMD, followed by LGMD R9 FKRP-related (11.1%), and LGMD R12 anoctamin5-related (7.1%). If we consider identified variants, then all but five were small-scale variants. One large gene deletion was identified in the LAMA2 gene and two deletions in each of CAPN3 and SGCG. We performed comparison our result with other published studies. The results obtained in the Czech LGMD population clearly differ from the outcome of other LGMD populations in two aspects-we have a more significant proportion of patients with LGMD R1 calpain3-related and a smaller proportion of LGMD R2 dysferlin-related.


Ab Initio Cyclic Voltammetry on Cu(111), Cu(100) and Cu(110) in Acidic, Neutral and Alkaline Solutions.
Electrochemical reactions depend on the electrochemical interface between the electrode surfaces and the electrolytes. To control and advance electrochemical reactions there is a need to develop realistic simulation models of the electrochemical interface to understand the interface from an atomistic point-of-view. Here we present a method for obtaining thermodynamic realistic interface structures, a procedure we use to derive specific coverages and to obtain ab initio simulated cyclic voltammograms. As a case study, the method and procedure is applied in a matrix study of three Cu facets in three different electrolytes. The results have been validated by direct comparison to experimental cyclic voltammograms. The alkaline (NaOH) cyclic voltammograms are described by H* and OH*, while in neutral medium (KHCO3 ) the CO 3* species are dominating and in acidic (KCl) the Cl* species prevail. An almost one-to-one mapping is observed from simulation to experiments giving an atomistic understanding of the interface structure of the Cu facets. Atomistic understanding of the interface at relevant eletrolyte conditions will further allow realistic modelling of electrochemical reactions of importance for future eletrocatalytic studies.


Children engage in competitive altruism.
Humans cultivate their reputations as good cooperators, sometimes even competing with group mates, to appear most cooperative to individuals during the process of selecting partners. To investigate the ontogenetic origins of such "competitive altruism," we presented 5- and 8-year-old children with a dyadic sharing game in which both children simultaneously decided how many rewards to share with each other. The children were either observed by a third-person peer or not. In addition, the children either knew that one of them would be picked for a subsequent collaborative game or had no such knowledge. We found that by 8 years of age, children were more generous in the sharing game not only when their behavior was observed by a third party but also when it could affect their chances of being chosen for a subsequent game. This is the first demonstration of competitive altruism in young children, and as such it underscores the important role of partner choice (and individual awareness of the process) in encouraging human cooperation from an early age.


Error Correction and the Structure of Inter-Trial Fluctuations in a Redundant Movement Task.
We study inter-trial movement fluctuations exhibited by human participants during the repeated execution of a virtual shuffleboard task. Focusing on skilled performance, theoretical analysis of a previously-developed general model of inter-trial error correction is used to predict the temporal and geometric structure of variability near a goal equivalent manifold (GEM). The theory also predicts that the goal-level error scales linearly with intrinsic body-level noise via the total body-goal sensitivity, a new derived quantity that illustrates how task performance arises from the interaction of active error correction and passive sensitivity properties along the GEM. Linear models estimated from observed fluctuations, together with a novel application of bootstrapping to the estimation of dynamical and correlation properties of the inter-trial dynamics, are used to experimentally confirm all predictions, thus validating our model. In addition, we show that, unlike "static" variability analyses, our dynamical approach yields results that are independent of the coordinates used to measure task execution and, in so doing, provides a new set of task coordinates that are intrinsic to the error-regulation process itself.


Partial duplication of the MLL oncogene in patients with aggressive acute myeloid leukemia.
MLL translocations generate a fusion gene between the 5' end of MLL and the 3' end of different partner genes. Several chromosomal mechanisms including complex and cryptic changes lead to these recombinations. Our objective was to analyze the molecular composition of chromosomes in complex karyotypes with specific MLL translocations. Fluorescence in situ hybridization (FISH) was performed in two acute leukemias (AL), one acute myeloid leukemia (AML) M5a, and one treatment-related-AL (t-AL), to investigate the nature of complex changes accompanying the respective t(9;11)(p22;q23)-MLL/AF9 and t(11;16)(q23;p13.3)-MLL/CBP. In the case with the MLL/AF9 chimeric transcript, duplication of a der(1) originated from an additional unbalanced translocation between the der(9)t(9;11) and a chromosome 1. The 5'AF9/3'MLL chimeric gene was present on both der(1). In the second case, there was a t(11;16)(q23;p13.3) producing one der(11) and two der(16) which derived from both homologs. One der(16) was present in multiple copies all containing the 5'CBP/3'MLL fusion gene. In both cases the 3' end of MLL was present in multiple copies. Mitotic recombination and non-disjunction may underlie the extra derivatives in both cases. In this genomic imbalance not only the 5'MLL but also the 3'end of MLL could play a critical role in the leukemic process.


Heart rate adjustment of exercise-induced ST-segment depression identifies men who benefit from a risk factor reduction program.
Whether subjects identified as being at increased risk of coronary heart disease (CHD) death by heart rate adjustment of exercise-induced ST-segment depression will benefit from therapy aimed at reducing risk factors has not been examined. Exercise ECGs were performed in 11,880 men from the Usual Care (UC) and Special Intervention (SI) groups of the Multiple Risk Factor Intervention Trial. UC men were referred to customary sources of care in the community; SI men received counseling on smoking cessation and dietary reduction of cholesterol, and stepped-care therapy for hypertension. An abnormal ST-segment response to exercise was defined according to standard criteria as > or = 100 microV of additional horizontal or downsloping ST-segment depression and by an ST-segment/heart rate (ST/HR) index >1.60 microV/bpm. After 7 years of follow-up, CHD mortality was significantly lower in SI than UC men with an abnormal ST/HR index (2.4%, 19/786 versus 5.3%, 39/729, P=.005) but was comparable in SI and UC men with a normal ST/HR index (1.6%, 84/5154 versus 1.3%, 70/5211, P=NS). Risk reduction in SI men with an abnormal ST/HR index was independent of age and other cardiac risk factors. In contrast, there was no significant difference in CHD death rate between the smaller groups of SI and UC men with an abnormal test by standard criteria (3.6%, 7/192 versus 2.7%, 5/186, P=NS). An abnormal ST/HR index identifies men in whom therapy aimed at reducing CHD risk factors reduces the risk of CHD death by 61%. These findings support the application of heart rate adjustment of ST depression for screening of asymptomatic subjects at increased risk of CHD to identify those who will benefit most from risk factor-reduction programs.


Cell-membrane-permeable and cytocompatible phospholipid polymer nanoprobes conjugated with molecular beacons.
To enable the visualization of the distribution and dynamics of intracellular biomolecules and thereby understand the mechanisms of intracellular bioreactions, we developed a specific functional nanoprobe through the combination of a well-designed, cytocompatible phospholipid polymer and molecular beacons (MBs). A water-soluble, amphiphilic phospholipid polymer, poly[2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)-co-N-succinimidyloxycarbonyl tetra(ethylene glycol) methacrylate] (PMBS), was synthesized and conjugated with MBs to form nanoprobes via a chemical reaction between the ester group of N-hydroxysuccinimide and the amine group of the MBs. Surface tension measurements indicated that the polymeric nanoprobes had different conformations in aqueous solution, specifically at a concentration of 1.0 mg/mL. The PMBS, containing the large, hydrophobic BMA, formed polymer aggregates. The carcinoma cells used to test the probes remained 100% viable after incubation with PMBS-MB probes. The polymeric nanoprobes demonstrated not only a high target specificity but also resistance to nonspecific adsorption of proteins compared with unconjugated MBs and were able to penetrate the cytoplasm of the cells, allowing the live imaging of mRNA. In summary, MPC polymer-MB nanoprobes have great potential for practical application for the noninvasive monitoring of intracellular biomolecules and bioreactions in real time.


An analytics approach to designing patient centered medical homes.
Recently the patient centered medical home (PCMH) model has become a popular team based approach focused on delivering more streamlined care to patients. In current practices of medical homes, a clinical based prediction frame is recommended because it can help match the portfolio capacity of PCMH teams with the actual load generated by a set of patients. Without such balances in clinical supply and demand, issues such as excessive under and over utilization of physicians, long waiting time for receiving the appropriate treatment, and non-continuity of care will eliminate many advantages of the medical home strategy. In this paper, by using the hierarchical generalized linear model with multivariate responses, we develop a clinical workload prediction model for care portfolio demands in a Bayesian framework. The model allows for heterogeneous variances and unstructured covariance matrices for nested random effects that arise through complex hierarchical care systems. We show that using a multivariate approach substantially enhances the precision of workload predictions at both primary and non primary care levels. We also demonstrate that care demands depend not only on patient demographics but also on other utilization factors, such as length of stay. Our analyses of a recent data from Veteran Health Administration further indicate that risk adjustment for patient health conditions can considerably improve the prediction power of the model.