Viability and growth characteristics of Lactobacillus in soymilk supplemented with B-vitamins.
Ten strains of Lactobacillus were evaluated for their viability in soymilk. Lactobacillus acidophilus ATCC 314, L. acidophilus FTDC 8833, L. acidophilus FTDC 8633 and L. gasseri FTDC 8131 displayed higher viability in soymilk and were thus selected to be evaluated for viability and growth characteristics in soymilk supplemented with B-vitamins. Pour plate analyses showed that the supplementation of all B-vitamins studied promoted the growth of lactobacilli to a viable count exceeding 7 log CFU/ml. alpha-Galactosidase specific activity of lactobacilli as determined spectrophotometrically showed an increase upon supplementation of B-vitamins. High-performance liquid chromatography analyses revealed that this led to increased hydrolysis of soy oligosaccharides and subsequently higher utilization of simple sugars. Production of organic acids as determined via high-performance liquid chromatography also showed an increase, accompanied by a decrease in pH of soymilk. Additionally, the supplementation of B-vitamins also promoted the synthesis of riboflavin and folic acid by lactobacilli in soymilk. Our results indicated that B-vitamin-supplemented soymilk is a good proliferation medium for strains of lactobacilli.


Post-genomics resources and tools for studying apicomplexan metabolism.
The phylum Apicomplexa comprises over 5000 species of obligate intracellular parasites, many responsible for diseases that significantly impact human health and economics. To aid drug development programs, global sequencing initiatives are generating increasing numbers of apicomplexan genomes. The challenge is how best to exploit these resources to identify effective therapeutic targets. Because of its important role in growth and maintenance, much interest has centred on metabolism. However, in the absence of detailed biochemical data, reconstructing the metabolic potential from a fully sequenced genome remains problematic. In this review current resources and tools facilitating the metabolic reconstruction for apicomplexans are examined. Furthermore, how these datasets can be utilized to explore the metabolic capabilities of apicomplexans are discussed and targets for therapeutic intervention are prioritized.


Guessing the future of endoscopic drainage of walled-off necrosis.
The endoscopic treatment of walled-off necrosis is rapidly evolving concurrently with an increasing number of endoscopic techniques, devices, and combined procedures. Thus, there is a growing armamentarium of alternatives for those patients in whom the conventional direct endoscopic necrosectomy is not enough. However, when the patient reaches this point he enters in an unexplored field and choosing the correct option can be challenging. Furthermore, there is no consensus on the number of endoscopic procedures to perform before considering that direct endoscopic necrosectomy has failed and therefore another strategy should be considered.


[The evaluation of effectiveness of scholastic programs in the prevention of consumption of tobacco, alcohol and cannabis: what do meta-analyses tell us?].
Consumption of tobacco, alcohol and illegal drugs is a major public health problem in developed countries. The aim of the study is to describe the impact and associated characteristics of preventive programs addressed at those problems in the school setting. Meta-analysis focusing on evaluations of programs focusing on smoking, alcohol and/or cannabis at the school setting are reviewed. The search was done at Cochrane Library and Medline databases of articles published between 1993 and 1999, and including as keywords programs, education, drugs prevention, prevention, smoking, alcohol, school, adolescence, teenagers, young people, evaluation, health education, effectiveness, review, meta-analysis. We found 5 meta-analysis of programs summarizing the effect of preventive programs, most of them dealing with legal and illegal drugs. However, most of the interventions reporting changes in behavior measured only smoking. More effective interventions addressed social influences, used active methodology and were implemented by teachers or peers. The importance of booster sessions, the quality of implementation and thorough evaluation is stressed. Overall, meta-analysis of evaluated programs shows a small effect, although the population impact may be relevant. Some limitations point to new areas of interest for future research.


Nursing students' perception regarding predicting factors of drugs use.
The study on the perception of 264 (33.2%) nursing students from the Professionalization and Regular groups regarding predicting factors of drugs consumption shows these students consume alcohol and tobacco and view alcohol as a leading factor in the consumption of drugs. The Professionalization group consumes tranquilizers and stimulants at a higher rate than the Regular group. The Professionalization students argue that they have to deal with an excessive personal load: career, job, family and stress. According to them, these factors motivate the consumption of tranquilizers and stimulants. The Professionalization group views the family and religion as protective factors; friends and school, on the other hand, are considered risk factors. Both groups consider drug users as amoral and addicts. The present study provides indicators that can support real actions aimed at improving the education of nursing personnel.


Direct oral anticoagulants--interference with laboratory tests and mechanism of action.
Direct oral anticoagulants (DOACs) have been established and already registered for clinical use on a wide basis in the United States and Europe. Different from the vitamin K antagonists (VKA), their mode of action is based on the direct inhibition of the single coagulation enzymes factor Xa or IIa. Other laboratory tests of hemostasis, such as the global tests prothrombin time (PT/INR) and activated partial thromboplastin time (APTT), or various functional coagulation assays involving generation of factor Xa or IIa for their endpoints, can be negatively influenced by the presence of the anticoagulant in the test sample. This interference has been well documented for rivaroxaban, apixaban, and dabigatran and is most prominent during the first hours after intake of the respective agent. Thus, the potential influence of DOACs has always to be considered when interpreting abnormal functional coagulation assays.


Brain clathrin: immunofluorescent patterns in cultured cells and tissues.
High-purity bovine brain clathrin elicited antibodies, which were separated by affinity chromatography on clathrin conjugated with CNBr-activated Sepharose 4B. Indirect immunofluorescent labeling on cultured rat fibroblasts showed the characteristic dotted fluorescence throughout the entire cytoplasm and concentrated patches of fluorescence in areas where the Golgi apparatus and GERL (Golgi apparatus-endoplasmic reticulum-lysosome complex) exist next to the nucleus. Cerebellar tissue sections exhibited profuse immunofluorescence in the granular layer; dissociated cultures of neonatal rat cerebellar cells showed intense fluorescence in the cytoplasm and processes of granule cell neurons. The data suggest that clathrin is an abundant protein distinctly localized in the cytoplasm of cells and clearly correlated in its distribution and arrangement with actin stress fibers.


Nacre-like ceramic composites: Properties, functions and fabrication in the context of dental restorations.
Dental restorations are in increasing demand, yet their success rate strongly decreases after 5-10 years post-implantation, attributed in part to mismatching properties with the surrounding buccal environment that causes failures and wear. Among current research to address this issue, biomimetic approaches are promising. Nacre-like ceramic composites are particularly interesting because they combine multiple antagonistic properties making them more resistant to failure in harsh environment than other materials. With the rapid progress in 3D printing producing nacre-like structures has open up new opportunities not yet realised. In this paper, nacre-like composites of various compositions are reviewed in the context of hypothetical biomimetic dental restorations. Their structural, functional and biological properties are compared with those of dentin, enamel, and bone to determine which composition would be the most suitable for each of the 3 mineralized regions found in teeth. The role of complex microstructures and mineral orientations are discussed as well as 3D printing methods that allow the design and fabrication of such complex architectures. Finally, usage of these processes and anticipated prospects for next generation biomimetic dental replacements are discussed to suggest future research directions in this area. STATEMENT OF SIGNIFICANCE: With the current ageing population, dental health is a major issue and current dental restorations still have shortcomings. For the next generation of dental restorations, more biomimetic approaches would be desirable to increase their durability. Among current materials, nacre-like ceramic composites are interesting because they can approach the various structural properties found in the different parts of our teeth. Furthermore, it is also possible to embed self-sensing functionalities to enable monitoring of oral health. Finally, new recent 3D printing technologies now permit the fabrication of complex shapes with local compositions and local microstructures. With this current status of the research, we anticipate new dental restorations designs and highlight the remaining gaps and issues to address.


Chimeric tick-borne encephalitis/dengue virus is attenuated in Ixodes scapularis ticks and Aedes aegypti mosquitoes.
In an effort to derive an efficacious live attenuated vaccine against tick-borne encephalitis, we generated a chimeric virus bearing the structural protein genes of a Far Eastern subtype of tick-borne encephalitis virus (TBEV) on the genetic background of recombinant dengue 4 (DEN4) virus. Introduction of attenuating mutations into the TBEV envelope protein gene, as well as the DEN4 NS5 protein gene and 3' noncoding region in the chimeric genome, results in decreased neurovirulence and neuroinvasiveness in mice, and restricted replication in mouse brain. Since TBEV and DEN4 viruses are transmitted in nature by ticks and mosquitoes, respectively, it was of interest to investigate the infectivity of the chimeric virus for both arthropod vectors. Therefore, parental and chimeric viruses were tested for growth in mosquito and tick cells and for oral infection in vivo. Although all chimeric viruses demonstrated moderate levels of replication in C6/36 mosquito cells, they were unable to replicate in ISE6 tick cells. Further, the chimeric viruses were unable to infect or replicate in Aedes aegypti mosquitoes and Ixodes scapularis tick larvae. The poor infectivity for both potential vectors reinforces the safety of chimeric virus-based vaccine candidates for the environment and for use in humans.


Nature and magnitude of aromatic stacking of nucleic acid bases.
This review summarises recent advances in quantum chemical calculations of base-stacking forces in nucleic acids. We explain in detail the very complex relationship between the gas-phase base-stacking energies, as revealed by quantum chemical (QM) calculations, and the highly variable roles of these interactions in nucleic acids. This issue is rarely discussed in quantum chemical and physical chemistry literature. We further extensively discuss methods that are available for base-stacking studies, complexity of comparison of stacking calculations with gas phase experiments, balance of forces in stacked complexes of nucleic acid bases, and the relation between QM and force field descriptions. We also review all recent calculations on base-stacking systems, including details analysis of the B-DNA stacking. Specific attention is paid to the highest accuracy QM calculations, to the decomposition of the interactions, and development of dispersion-balanced DFT methods. Future prospects of computational studies of base stacking are discussed.


Relationships among stress, emotional intelligence, cognitive intelligence, and cytokines.
The brain has multiple functions, and its structures are very closely related to one another. Thus, the brain areas associated with stress, emotion, and intelligence are closely connected. The purpose of this study was to investigate the multiple associations between stress and emotional intelligence (EI), between EI and intelligence quotient (IQ), between cytokines and stress, and between cytokines and IQ. We measured the stress, EI, cognitive intelligence using IQ, and cytokine levels of 70 healthy subjects. We also analyzed the association of cytokines with IQ according to hemispheric dominance using the brain preference indicator (BPI). We found significant negative correlations between stress and the components of EI, such as emotional awareness and expression, emotional thinking, and emotional regulation. High levels of anger, which is a component of stress, were significantly related to poor emotional regulation. Additionally, emotional application was positively correlated with full-scale IQ scores and scores on the vocabulary, picture arrangement, and block design subtests of the IQ test. High IL-10 levels were significantly associated with low stress levels only in the right-brain-dominant group. High IL-10 and IFN-gamma levels have been associated with high scores of arithmetic intelligence. TNF-alpha and IL-6 were negatively associated with vocabulary scores and full-scale IQ, but IL-10 and IFN-gamma were positively associated with scores on the arithmetic subtest in left-brain-dominant subjects. On the other hand, IL-10 showed positive correlations with scores for vocabulary and for vocabulary and arithmetic in right-brain-dominant subjects. Furthermore, we found significant linear regression models which can show integrative associations and contribution on emotional and cognitive intelligence. Thus, we demonstrated that cytokines, stress, and emotional and cognitive intelligence are closely connected one another related to brain structure and functions. Also, the pro-inflammatory cytokines TNF-alpha and IL-6 had negative effects, whereas the anti-inflammatory cytokines (e.g., IL-10 and IFN-gamma) showed beneficial effects, on stress levels, and multiple dimensions of emotional and cognitive intelligence. Additionally, these relationships among cytokines, stress, and emotional and cognitive intelligence differed depending on right and left hemispheric dominance.


The testicular cycle of a percoid teleost--Nandus nandus (Ham.).
Small paired testes of Nandus nandus are situated posteriorly in the body cavity. They open posteriorly in a common sperm duct. A urinogenital sinus is present. Each testis consists of a large number of seminiferous tubules extending from the periphery towards the centre. The seminiferous tubules are separated from each other by a layer of interstitial tissue. 6 different stages of spermatogenesis are recognised. On the basis of morphological and histological changes in the testes during different months of the year, the reproduvtice cycle has been divided into post-spawning (October to December), pre-spawning (January to March) and spawning (April to August) periods. The monthly volume of testes is in direct correlation with the monthly changes in water temperature. Statistical observations indicate that the process of spermatogenesis is very active during pre-spawning period. The relative number of spermatozoa is maximum in July (69.89%), suddenly decreases in August (54.28%) and continues to decrease upto October (49.66%) indicating the maximum spawning in July and August.


Direct observation of vibrational coherence in bacterial reaction centers using femtosecond absorption spectroscopy.
It is shown that vibrational coherence modulates the femtosecond kinetics of stimulated emission and absorption of reaction centers of purple bacteria. In the DLL mutant of Rhodobacter capsulatus, which lacks the bacteriopheophytin electron acceptor, oscillations with periods of approximately 500 fs and possibly also of approximately 2 ps were observed, which are associated with formation of the excited state. The kinetics, which reflect primary processes in Rhodobacter sphaeroides R-26, were modulated by oscillations with a period of approximately 700 fs at 796 nm and approximately 2 ps at 930 nm. In the latter case, at 930 nm, where the stimulated emission of the excited state, P*, is probed, oscillations could only be resolved when a sufficiently narrow (10 nm) and concomitantly long pump pulse was used. This may indicate that the potential energy surface of the excited state is anharmonic or that low-frequency oscillations are masked when higher frequency modes are also coherently excited, or both. The possibility is discussed that the primary charge separation may be a coherent and adiabatic process coupled to low-frequency vibrational modes.


Cyclooxygenase-1 or -2--which one mediates lipopolysaccharide-induced hypothermia?
Systemic inflammation is associated with either fever or hypothermia. Fever, a response to mild systemic inflammation, is mediated by cyclooxygenase (COX)-2 and not by COX-1. However, it is still disputed whether COX-2, COX-1, neither, or both mediate(s) responses to severe systemic inflammation, and, in particular, the hypothermic response. We compared the effects of SC-236 (COX-2 inhibitor) and SC-560 (COX-1 inhibitor) on the deep body temperature (T(b)) of rats injected with a lower (10 microg/kg i.v.) or higher (1,000 microg/kg i.v.) dose of LPS at different ambient temperatures (T(a)s). At a neutral T(a) (30 degrees C), the rats responded to LPS with a polyphasic fever (lower dose) or a brief hypothermia followed by fever (higher dose). SC-236 (2.5 mg/kg i.v.) blocked the fever induced by either LPS dose, whereas SC-560 (5 mg/kg i.v.) altered neither the febrile response to the lower LPS dose nor the fever component of the response to the higher dose. However, SC-560 blocked the initial hypothermia caused by the higher LPS dose. At a subneutral T(a) (22 degrees C), the rats responded to LPS with early (70-90 min, nadir) dose-dependent hypothermia. The hypothermic response to either dose was enhanced by SC-236 but blocked by SC-560. The hypothermic response to the higher LPS dose was associated with a fall in arterial blood pressure. This hypotensive response was attenuated by either SC-236 or SC-560. At the onset of LPS-induced hypothermia and hypotension, the functional activity of the COX-1 pathway (COX-1-mediated PGE(2) synthesis ex vivo) increased in the spleen but not liver, lung, kidney, or brain. The expression of splenic COX-1 was unaffected by LPS. We conclude that COX-1, but not COX-2, mediates LPS hypothermia, and that both COX isoforms are required for LPS hypotension.


Natural enemies of herbivores maintain their biological control potential under short-term exposure to future CO2, temperature, and precipitation patterns.
Climate change will profoundly alter the physiology and ecology of plants, insect herbivores, and their natural enemies, resulting in strong effects on multitrophic interactions. Yet, manipulative studies that investigate the direct combined impacts of changes in CO2, temperature, and precipitation on the third trophic level remain rare. Here, we assessed how exposure to elevated CO2, increased temperature, and decreased precipitation directly affect the performance and predation success of species from four major groups of herbivore natural enemies: an entomopathogenic nematode, a wolf spider, a ladybug, and a parasitoid wasp. A four-day exposure to future climatic conditions (RCP 8.5), entailing a 28% decrease in precipitation, a 3.4°C raise in temperature, and a 400 ppm increase in CO2 levels, slightly reduced the survival of entomopathogenic nematodes, but had no effect on the survival of other species. Predation success was not negatively affected in any of the tested species, but it was even increased for wolf spiders and entomopathogenic nematodes. Factorial manipulation of climate variables revealed a positive effect of reduced soil moisture on nematode infectivity, but not of increased temperature or elevated CO2. These results suggest that natural enemies of herbivores may be well adapted to short-term changes in climatic conditions. These findings provide mechanistic insights that will inform future efforts to disentangle the complex interplay of biotic and abiotic factors that drive climate-dependent changes in multitrophic interaction networks.


Association Between Parental Social Interaction and Behavior Problems in Offspring: a Population-Based Study in Japan.
Research in parental social support has chiefly examined received social support. Studies have suggested that provided social support may also be protective for child mental health problems. We aim to investigate the association between parental social interaction (both received and provided social support) and offspring behavior problems. We analyzed the data of 982 households, including 1538 children aged 4 to 16 years, from the Japanese Study of Stratification, Health, Income, and Neighborhood (J-SHINE) survey conducted over 2010-2011. We used a 5-point Likert scale to assess social interaction including parental emotional and instrumental support received from and provided to the spouse, other co-residing family members, non-co-residing family members or relatives, neighbors, and friends. Behavior problems in offspring were assessed using parental responses to the Strengths and Difficulties Questionnaire. Associations between parental social interaction and behavior problems were analyzed using ordered logistic regression. We found that higher maternal social interaction is significantly associated with lower odds of both difficult and prosocial behavior problems, while the same associations were not found for paternal social interaction. Further, maternal provided social support showed an independent negative association with prosocial behavior problems in offspring, even when adjusted for received maternal social support and paternal social interaction. This study showed that maternal social interaction, but not paternal social interaction, might have a protective effect on offspring behavior problems. Further study is required to investigate the effect of the intervention to increase social participation among mothers whose children have behavior problems.


Decreased expression of TFF2 and decreased αGlcNAc glycosylation are malignant biomarkers of pyloric gland adenoma of the duodenum.
Pyloric gland adenoma (PGA) is a duodenal neoplasm expressing MUC6 and is often associated with high-grade dysplasia and adenocarcinoma. MUC6 secreted from the pyloric gland cells carries unique O-glycans exhibiting terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). The small peptide trefoil factor 2 (TFF2) is also secreted from pyloric gland cells and binds to αGlcNAc. We recently demonstrated that αGlcNAc serves as a tumor suppressor for gastric neoplasm including PGA, but the significance of TFF2 expression remains unknown. We examined 20 lesions representing low- and high-grade PGA in 22 cases by immunohistochemistry for αGlcNAc, TFF2, MUC6, MUC5AC, MUC2 and p53. αGlcNAc, TFF2 and MUC6 were co-expressed on the cell surface and a dot-like pattern in the cytosol in low-grade PGA lesions. High-grade PGA also expressed MUC6, but reduced αGlcNAc and TFF2 expression. The ratios of αGlcNAc or TFF2 to MUC6 score in high-grade PGA were significantly lower than low-grade PGA (P < 0.001). Co-expression of αGlcNAc-glycosylated MUC6 and TFF2 in PGA suggests the existence of αGlcNAc/TFF2 form complex in PGA cells, a finding consistent with our observations in non-neoplastic Brunner's gland cells. The decreased αGlcNAc and TFF2 expression are associated with high grade atypical cells, indicative of the malignant potential of PGA.


[Development of a differentiation scheme for Hafnia using the H antigen].
The authors suggest a differentiation scheme for Hafnia bacteria by the H-antigen, including 36 varieties of the flagellar antigen. A collection of H-test-strains which can be used in elaboration of technology of preparation of Hafnia H-sera was determined.


[Urogenital alterations in hereditary and sporadic neurodegenerative ataxias].
Sporadic and hereditary ataxias (HA) represent a group of clinically and genetically heterogeneous syndromes characterized by spinocerebellar degeneration producing a motoneuron coordination disorder. In these diseases urinary and sexual symptoms are commonly associated to the neurological alterations. To define the prevalence of functional low urinary tract symptoms in an ataxic population and to compare them with the symptomatology control a group of in healthy subjects. An observational, descriptive, transversal study of 491 subjects recruited from the HA regional associations of Spain was conducted. In addition, a case-control study of prevalent ataxic patients and healthy subjects matched by sex and age was also performed. Among 195 patients included, 138 (70.8 %) had Friedreich ataxia (FA) and 57 (29.2 %) non-Friedreich ataxia (nFA). Global mean age was 32.3 years in FA and 43.7 in nFA patients (p < 0.05). Combined irritative and obstructive symptoms were present in 48.7 %, only irritative in 16.4 % and obstructive in 15 % of patients. Erectile dysfunction in 30.3 % (p < 0.01) and decreased libido in 13.4 % (p < 0.01), were the most common sexual problems. In HA, urinary symptoms are present in 80 % of patients, with mainly irritative symptoms in 2/3 of them. A complete urodynamic evaluation in symptomatic patients is recommended in order to characterize potential neurogenic vesico-urethral dysfunction. Even though sexual dysfunction may be related to neurological causes, additional etiologic organic factors should be excluded.


Predictors of HPV incidence and clearance in a cohort of Brazilian HIV-infected women.
Persistent infection with high-risk human papillomavirus (HR-HPV) is necessary for the development of precursor lesions and cervical cancer. HPV infection among women living with HIV/AIDS (WLHA) occurs more frequently, presents a higher rate of persistent infections and an earlier progression to cancer. We aimed to evaluate HR-HPV prevalence, incidence and clearance, and its association with HIV viral suppression, immunological response and other risk factors among WLHA followed at an STD/HIV reference center. This was a cohort study conducted at a reference center for STD/AIDS in Northeastern Brazil from September 2013 to September 2015. Follow-up visits were conducted at 6 and 12 months after enrolment, where socio-epidemiological data were obtained. Cervical samples were collected for conventional cytology and HPV DNA research (PCR COBAS® Roche) in addition to blood samples for CD4+ T lymphocyte count and HIV viral load. We prospectively evaluated 333 women. HR-HPV DNA prevalence was 33.3% at baseline. HPV-16 was present in 5.1%, HPV-18 in 3.9% and 29.4% WLHA had other HR-HPV (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). The HR-HPV incidence during the follow-up was 10.8%, at the 6-month visit was 7.7% and at the 12-month visit was 3.7%. Variables associated with HR-HPV incidence were: nulliparity, combined oral contraceptive use and detectable HIV viral load. The HR-HPV clearance rate was 41.7% and was associated with age >30 years and lymphocyte T CD4 count >500 cells/mm3 at enrolment. These findings contribute to the knowledge about a group of women that need more careful HPV screening and describe the association between an efficient immunological response and HIV viral suppression with lower incidence and increased clearance of HR-HPV.


Metagenomics as a preliminary screen for antimicrobial bioprospecting.
Since the composition of soil directs the diversity of the contained microbiome and its potential to produce bioactive compounds, many studies has been focused on sediment types with unique features characteristic of extreme environments. However, not much is known about the potential of microbiomes that inhabit the highly saline and hot Red Sea lagoons. This case study explores mangrove mud and the microbial mat of sediments collected from the Rabigh harbor lagoon and Al Kharrar lagoon for antimicrobial bioprospecting. Rabigh harbor lagoon appears the better location, and the best sediment type for this purpose is mangrove mud. On the other hand, Al Kharrar lagoon displayed increased anaerobic hydrocarbon degradation and an abundance of bacterial DNA associated with antibiotic resistance. Moreover, our findings show an identical shift in phyla associated with historic hydrocarbon contamination exposure reported in previous studies (that is, enrichment of Gamma- and Delta-proteobacteria), but we also report that bacterial DNA sequences associated with antibiotic synthesis enzymes are derived from Gamma-, Delta- and Alpha-proteobacteria. This suggests that selection pressure associated with hydrocarbon contamination tend to enrich the bacterial classes DNA associated with antibiotic synthesis enzymes. Although Actinobacteria tends to be the common target for research when it comes to antimicrobial bioprospecting, our study suggests that Firmicutes (Bacilli and Clostridia), Bacteroidetes, Cyanobacteria, and Proteobacteria should be antimicrobial bioprospecting targets as well. To the best of our knowledge, this is the first metagenomic study that analyzed the microbiomes in Red Sea lagoons for antimicrobial bioprospecting.


Economic impact of compliance to treatment with antidiabetes medication in type 2 diabetes mellitus: a review paper.
Suboptimal compliance and failure to persist with antidiabetes therapies are of potential economic significance. The present research aims to describe the impact of poor compliance and persistence with antidiabetes medications on the cost of healthcare or its components for patients with type 2 diabetes mellitus (T2DM). Literature search was conducted in PubMed for relevant articles published in the period between 1 January 2000 and 30 April 2009. Thus, it is possible that relevant articles not listed in PubMed, but available in other databases are not included in the current review. Studies describing economic consequence of compliance and/or persistence with pharmaceutical antidiabetes treatment were identified. The variability in the studies reviewed was high, making it extremely difficult to make a comparison between them. Of 449 articles corresponding to the primary search algorithm, 12 studies (all conducted in USA) fulfilled the inclusion criteria regarding the economic impact of compliance and/or persistence with treatment on the overall cost of T2DM care or its components. Compliance was assessed via medication possession ratio (MPR) in ten studies, where it ranged from 0.52 to 0.93 depending on regimen. Persistence was assessed in one study. Mean total annual costs per T2DM patient varied between the studies, ranging from $4570 to $17338. In seven studies, medication compliance was inversely associated with total healthcare costs, while in four other studies inverse associations between medication compliance and hospitalisation costs were reported. In one study increased adherence did not change overall healthcare costs. Improved compliance may lead to reductions of the total healthcare costs in T2DM, Further research is needed in countries other than the US to assess impact of compliance and persistence to pharmacotherapy on T2DM costs in country-specific settings.


Cytosolic iron-sulfur protein assembly system identifies clients by a C-terminal tripeptide.
The eukaryotic cytosolic Fe-S protein assembly (CIA) machinery inserts iron-sulfur (Fe-S) clusters into cytosolic and nuclear proteins. In the final maturation step, the Fe-S cluster is transferred to the apo-proteins by the CIA-targeting complex (CTC). However, the molecular recognition determinants of client proteins are unknown. We show that a conserved [LIM]-[DES]-[WF]-COO- tripeptide present at the C-terminus of clients is necessary and sufficient for binding to the CTC in vitro and directing Fe-S cluster delivery in vivo. Remarkably, fusion of this TCR (target complex recognition) signal enables engineering of cluster maturation on a non-native protein via recruitment of the CIA machinery. Our study significantly advances our understanding of Fe-S protein maturation and paves the way for bioengineering applications.


Bayesian deconvolution analysis of pulsatile hormone concentration profiles.
Many hormones are secreted into the circulatory system in a pulsatile manner and are cleared exponentially. The most common method of analyzing these systems is to deconvolve the hormone concentration into a secretion function and a clearance function. Accurate estimation of the model parameters depends on the number and location of the secretion pulses. To date, deconvolution analysis assumes the number and approximate location of these pulses are known a priori. In this article, we present a novel Bayesian approach to deconvolution that jointly models the number of pulses along with all other model parameters. Our method stochastically searches for the secretion pulses. This is accomplished by viewing the set of parameters that define the pulses as a point process. Pulses are determined by a birth-death process which is embedded in Markov chain Monte Carlo algorithm. This idea originated with Stephens (2000, Annals of Statistics 28, 40-74) in the context of finite mixture model density estimation, where the number of mixture components is unknown. There are several advantages that our model enjoys over the traditional frequentist approaches. These advantages are highlighted with four datasets consisting of serum concentration levels of luteinizing hormone obtained from ovariectomized ewes.


Signals from cone photoreceptors to L-type horizontal cells are differentially modulated by low calcium in carp retina.
Ca2+ plays crucial roles in both phototransduction and calcium-dependent glutamate release from the photoreceptor terminal. Modulation, by lowering extracellular Ca2+, of red-sensitive (R-) and short wavelength-sensitive (S-) cone-driven light responses of L-type horizontal cells (LHCs) was studied in the isolated superfused carp retina using intracellular recording techniques. Low Ca2+ (nominally Ca2+-free) Ringer's reduced responses of LHCs to both green (500 nm) and red (680 nm) flashes in darkness, with the former being suppressed more substantially than the latter. This differential suppression became more significant when contribution of R-cones to the green-light-induced responses was diminished by a moderate red (680 nm) background light. Application of IBMX, an inhibitor of phosphodiesterase (PDE), increased LHC responses to both red and green flashes equally, resembling the effect of low Ca2+ on phototransduction. In addition, photopic electroretinographic P III responses, reflecting the activity of cones, to red flashes were more potentiated by low Ca2+, compared to those to green flashes, whilst they were both equally potentiated by IBMX. Furthermore, low Ca2+ caused a more pronounced suppression of LHC responses to red flashes than those to green flashes in the presence of IBMX. It is postulated that reduction of LHC responses in low Ca2+ may be due to the 'saturation suppression' caused by the increased glutamate release from the photoreceptor terminal and the differential modulation may reflect a consequence of the dual action of low Ca2+ on the PDE activity in the photoreceptor outer segment and the synaptic strength between cones and LHCs.


Cancer stem cells and metastasis.
Cancer stem cells (CSCs) represent a subpopulation of tumour cells endowed with self-renewal and multi-lineage differentiation capacity but also with an innate resistance to cytotoxic agents, a feature likely to pose major clinical challenges towards the complete eradication of minimal residual disease in cancer patients. Operationally, CSCs are defined by their tumour-propagating ability when serially transplanted into immune-compromised mice and by their capacity to fully recapitulate the original heterogeneity of cell types observed in the primary lesions they are derived from. CSCs were first identified in haematopoietic malignancies and later in a broad spectrum of solid tumours including those of the breast, colon and brain. Notably, several CSC characteristics are relevant to metastasis, such as motility, invasiveness and, as mentioned above, resistance to DNA damage-induced apoptosis. Here, we have reviewed the current literature on the relation between CSCs and metastasis formation. Preliminary studies on cancer cell lines and patient-derived material suggest a rate-limiting role for stem-like cells in the processes of tumour cell dissemination and metastasis formation. However, additional studies are needed to deliver formal proof of their identity as the cell of origin of recurrences at distant organ sites. Nevertheless, several studies have already provided pre-clinical evidence of the efficacy of novel therapies directed against disseminated CSCs.


Nuclear transcription factors that bind to elements of the IL-2 promoter. Induction requirements in primary human T cells.
Prior studies have identified several elements that contribute to the activity of the IL-2 promoter in the stimulated T cell line, Jurkat. The sites and their corresponding nuclear binding factors include: NF-kappa B, AP-1, AP-3, OCT-1, and NF-AT. The latter "nuclear factor for activated T cells" likely contributes to the tissue specificity of IL-2 gene expression. Using electrophoretic mobility shift assays, we have studied these transcription factors in primary T cells from human blood to verify their presence in a physiologic setting and to identify the signals that stimulate factor activity. All factors are induced in the nuclei of T cells upon activation with mitogens but not with exogenous IL-2 growth factor. However, the signaling requirements and sensitivity to protein synthesis inhibitors differ considerably. Only the activities for NF-AT and AP-1 sites require two signals for optimal induction, i.e., PMA plus either lectin or antibody to the CD3 or CD28 surface molecules. Other factors are induced by lectin, antibody, and/or PMA alone. After appropriate stimulation, both NF-AT and AP-1 are peculiarly sensitive to the protein synthesis inhibitor anisomycin. Our data correlate the activity of NF-AT and AP-1 in gel shift assays with the two signals requirements for IL-2 gene expression.


Microtubule dynamics in nerve cells: analysis using microinjection of biotinylated tubulin into PC12 cells.
To study microtubule (MT) dynamics in nerve cells, we microinjected biotin-labeled tubulin into the cell body of chemically fused and differentiated PC12 cells and performed the immunofluorescence or immunogold procedure using an anti-biotin antibody followed by secondary antibodies coupled to fluorescent dye or colloidal gold. Incorporation of labeled subunits into the cytoskeleton of neurites was observed within minutes after microinjection. Serial electron microscopic reconstruction revealed that existing MTs in PC12 neurites incorporated labeled subunits mainly at their distal ends and the elongation rate of labeled segments was estimated to be less than 0.3 micron/min. Overall organization of MTs in the nerve cells was different from that in undifferentiated cells such as fibroblasts. Namely, we have not identified any MT-organizing centers from which labeled MTs are emanating in the cell bodies of the injected cells. Stereo electron microscopy revealed that some fully labeled segments seemed to start in the close vicinity of electron dense material within the neurites. This suggests new nucleation off some structures in the neurites. We have also studied the overall pattern of the incorporation of labeled subunits which extended progressively from the proximal part of the neurites toward their tips. To characterize the mechanism of tubulin incorporation, we have measured mean density of gold labeling per unit length of labeled segments at different parts of the neurites. The results indicate access of free tubulin subunits into the neurites and local incorporation into the neurite cytoskeleton. Our results lead to the conclusion that MTs are not static polymers but dynamic structures that continue to elongate even within the differentiated nerve cell processes.


Selection and determination of beam weights based on genetic algorithms for conformal radiotherapy treatment planning.
A genetic algorithm has been used to optimize the selection of beam weights for external beam three-dimensional conformal radiotherapy treatment planning. A fitness function is defined, which includes a difference function to achieve a least-square fit to doses at preselected points in a planning target volume, and a penalty item to constrain the maximum allowable doses delivered to critical organs. Adjustment between the dose uniformity within the target volume and the dose constraint to the critical structures can be achieved by varying the beam weight variables in the fitness function. A floating-point encoding schema and several operators, like uniform crossover, arithmetical crossover, geometrical crossover, Gaussian mutation and uniform mutation, have been used to evolve the population. Three different cases were used to verify the correctness of the algorithm and quality assessment based on dose-volume histograms and three-dimensional dose distributions were given. The results indicate that the genetic algorithm presented here has considerable potential.


Protective behavioral strategies for sexual aggression and risky sexual behavior.
Sexual aggression (SA) is a serious public-health problem on college campuses, and there is a pressing need for basic research fostering the development of novel prevention strategies. The current study (a) developed measures of protective behavioral strategies (PBS) for sexual aggression (SA) and risky sex (RS); (b) characterized college men's PBS use; and (c) evaluated whether those who reported engaging in SA and RS showed lower PBS use. Undergraduate men from two universities (n = 567) who endorsed sexual attraction toward women completed measures of PBS, SA, RS, rape-supportive and sociosexual attitudes, and alcohol consumption. On average, participants reported using PBS for SA and RS fairly often, but a sizeable number indicated that they seldom or never used the strategies. Men who reported SA engagement in the last year, relative to their peers, endorsed sharply lower reliance on SA PBS and RS PBS. Men who reported at least one RS behavior in the last year used RS PBS far less often than their peers. The PBS measures converged as expected with other attitudinal and behavioral measures. The new PBS measures reference cognitive-behavioral approaches that a large percentage of college men use on a regular basis, making them potentially acceptable prevention targets. Further, men at greater risk of exhibiting SA are much less likely to take steps to reduce the risks associated with sexual behavior, in comparison with their peers. Thus, future work could evaluate the potential usefulness of incorporating PBS for SA and RS into primary prevention programming in both domains.


Antipsychotic induced weight gain in schizophrenia:mechanisms and management.
The aim of the present paper was to describe the mechanisms and management of antipsychotic-induced weight gain in schizophrenia patients. A comprehensive literature review of all available articles on the mechanisms and management of antipsychotic-induced weight gain was done by searching databases PsychINFO and PubMed. A summary of the available guidelines for monitoring of antipsychotic-induced weight gain and metabolic syndrome is also provided. There has been a substantial increase in the number of studies investigating the mechanisms and management of antipsychotic-induced weight gain after 2002. These include advances in the understanding of pharmacogenomics of weight gain and several randomized controlled trials (RCTs) evaluating pharmacological and psychological treatments to promote weight loss. The most effective strategy for prevention of weight gain is the choice of antipsychotic medication with low weight gain potential. In individuals with established weight gain and metabolic issues, switching to an antipsychotic agent with lower weight gain potential and/or lifestyle modifications with physical activity are most effective in promoting weight loss. Pharmacological agents such as orlistat and sibutramine are effective in general obesity but have not been sufficiently evaluated in antipsychotic-induced weight gain. The case to prescribe routine pharmacological treatment to promote weight loss is weak. Long-term, pragmatic studies are required to inform clinical practice. Weight gain in schizophrenia is associated with significant physical and psychological morbidity. Achieving an optimal trade-off between effectiveness and side-effects of antipsychotic agents, although difficult, is achievable. This should be based on three main principles: (i) a shared decision-making model between the patient, clinician and carer(s) when choosing an antipsychotic; (ii) a commitment to baseline and follow-up monitoring with explicit identification of the responsible individual or team; and (iii) the adoption of clear structured protocols for clinicians to follow in case of clinically significant weight gain and metabolic issues, which should incorporate greater collaboration between various health professionals from psychiatric and medical specialist services.


Genistein inhibits carotid sinus baroreceptor activity in anesthetized male rats.
To study the effect of genistein (GST) on carotid baroreceptor activity (CBA). The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. GST at 50, 100, and 200 micromol/L inhibited the CBA, which shifted FCCB to the right and downward, with a marked decrease in peak slope and peak integral value of carotid sinus nerve discharge in a concentration-dependent manner. Pretreatment with 100 micromol/L NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, did not affect the effect of GST on CBA. Pretreatment with 500 nmol/L Bay K8644, an agonist of calcium channels, could completely abolish the effect of GST on CBA. A potent inhibitor of tyrosine phosphatase, sodium orthovanadate (1 mmol/L), could attenuate the inhibitory effect of GST. GST inhibits CBA, and the effect may be mediated by protein tyrosine kinase inhibition and a decrease in Ca2+ influx through the stretch-activated channels.


Copy number variation of the beta defensin gene cluster on chromosome 8p influences the bacterial microbiota within the nasopharynx of otitis-prone children.
As there is increasing evidence that aberrant defensin expression is related to susceptibility for infectious disease and inflammatory disorders, we sought to determine if copy number of the beta-defensin gene cluster located on chromosome 8p23.1 (DEFB107, 106, 105, 104, 103, DEFB4 and SPAG11), that shows copy number variation as a block, was associated with susceptibility to otitis media (OM). The gene DEFB103 within this complex encodes human beta defensin-3 (hBD-3), an antimicrobial peptide (AP) expressed by epithelial cells that line the mammalian airway, important for defense of mucosal surfaces and previously shown to have bactericidal activity in vitro against multiple human pathogens, including the three that predominate in OM. To this end, we conducted a retrospective case-control study of 113 OM prone children and 267 controls aged five to sixty months. We identified the copy number of the above defined beta-defensin gene cluster (DEFB-CN) in each study subject by paralogue ratio assays. The mean DEFB-CN was indistinguishable between subjects classified as OM prone based on a recent history of multiple episodes of OM and control subjects who had no history of OM (4.4 ± 0.96 versus 4.4 ± 1.08, respectively: Odds Ratio [OR]: 1.16 (95% CI: 0.61, 2.20). Despite a lack of direct association, we observed a statistically significant correlation between DEFB-CN and nasopharyngeal bacterial colonization patterns. Collectively, our findings suggested that susceptibility to OM might be mediated by genetic variation among individuals, wherein a DEFB-CN less than 4 exerts a marked influence on the microbiota of the nasopharynx, specifically with regard to colonization by the three predominant bacterial pathogens of OM.


Mechanism and energetics of 〈c + a〉 dislocation cross-slip in hcp metals.
Hexagonal close-packed (hcp) metals such as Mg, Ti, and Zr are lightweight and/or durable metals with critical structural applications in the automotive (Mg), aerospace (Ti), and nuclear (Zr) industries. The hcp structure, however, brings significant complications in the mechanisms of plastic deformation, strengthening, and ductility, and these complications pose significant challenges in advancing the science and engineering of these metals. In hcp metals, generalized plasticity requires the activation of slip on pyramidal planes, but the structure, motion, and cross-slip of the associated [Formula: see text] dislocations are not well established even though they determine ductility and influence strengthening. Here, atomistic simulations in Mg reveal the unusual mechanism of [Formula: see text] dislocation cross-slip between pyramidal I and II planes, which occurs by cross-slip of the individual partial dislocations. The energy barrier is controlled by a fundamental step/jog energy and the near-core energy difference between pyramidal [Formula: see text] dislocations. The near-core energy difference can be changed by nonglide stresses, leading to tension-compression asymmetry and even a switch in absolute stability from one glide plane to the other, both features observed experimentally in Mg, Ti, and their alloys. The unique cross-slip mechanism is governed by common features of the generalized stacking fault energy surfaces of hcp pyramidal planes and is thus expected to be generic to all hcp metals. An analytical model is developed to predict the cross-slip barrier as a function of the near-core energy difference and applied stresses and quantifies the controlling features of cross-slip and pyramidal I/II stability across the family of hcp metals.


Relational barriers to depression help-seeking in primary care.
To identify attitudinal and interpersonal barriers to depression care-seeking and disclosure in primary care and in so doing, evaluate the primary care paradigm for depression care in the United States. Fifteen qualitative focus group interviews in three cities. Study participants were English-speaking men and women aged 25-64 with first-hand knowledge of depression. Transcripts were analyzed iteratively for recurring themes. Participants expressed reservations about the ability of primary care physicians (PCPs) to meet their mental health needs. Specific barriers included problems with PCP competence and openness as well as patient-physician trust. While many reflected positively on their primary care experiences, some doubted PCPs' knowledge of mental health disorders and believed mental health concerns fell outside the bounds of primary care. Low-income participants in particular shared stories about the essentiality, and ultimate fragility, of patient-PCP trust. Patients with depression may be deterred from care-seeking or disclosure by relational barriers including perceptions of PCPs' mental health-related capabilities and interests. PCPs should continue to develop their depression management skills while supporting vigorous efforts to inform the public that primary care is a safe and appropriate venue for treatment of common mental health conditions.


Editor's Choice- Diagnosis of type 2 diabetes and prediabetes among patients with acute coronary syndromes.
Previously undetected dysglycaemia is common among patients with acute coronary syndromes (ACSs). The aim of this study was to identify the most reliable method of diagnosing type 2 diabetes mellitus (T2DM) and prediabetes in ACS patients. Patients admitted to the coronary care unit with ACSs and no previous history of T2DM were consecutively included in the study. Glucose metabolism was measured by glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) with a standard oral glucose tolerance test during hospital admission, and this process was repeated 3 months later. In this study, the diagnosis of T2DM required at least two measurements above the diabetes cut-off point according to current American Diabetes Association and World Health Organization criteria. A total of 250 patients were included in the study. T2DM was diagnosed in 7.2%. The sensitivities for detecting T2DM were 33.3%, 61.1% and 77.8% during admission and 27.8%, 61.1% and 72.2% at follow-up for HbA1c, FPG and 2hPG, respectively. The positive predictive values (PPVs) for diagnosing T2DM were 100%, 91.7% and 51.9% during admission and 71.4%, 91.7% and 65.0% at follow-up for HbA1c, FPG and 2hPG, respectively. The specificities and negative predictive values were high for all methods. By combining all measurements, the sensitivity was 100% and the PPV was 44.2%, while the combination of all HbA1c and FPG measurements provided 88.9% sensitivity and 80.0% PPV. Diagnosis of T2DM can be reliably carried out by repeated measurements of FPG and HbA1c in ACS patients, with limited added value of an oral glucose tolerance test.


Assessment of the environmental fate and ecotoxicity of N,N-diethyl-m-toluamide (DEET).
N,N-diethyl-m-toluamide (DEET) is a key active ingredient in many insect repellents available commercially throughout the world. Owing to its popularity among consumers for nearly 30 years, considerable work conducted in the past has demonstrated-and continues to demonstrate-that human exposure to DEET poses no significant health risk to the general population. The results of several studies reported in this paper describe more recent work to understand the environmental fate of DEET, particularly in surface waters and soil, and the potential hazards to aquatic and terrestrial organisms. In summary, DEET enters the environment through several pathways: directly into air during spray application; to surface water from overspray and indirectly via wastewater treatment plant (WTTP) discharges (as a result of washing of skin and laundering of clothing); or to soil via overspray and application of treated sewage as an amendment. Multimedia environmental fate modeling predicts that DEET entering the environment is retained either in receiving waters (∼79%) or in soil (∼21%). Based on its physicochemical properties, DEET is expected to be moderately mobile in the soil column. In surface waters and soil, DEET degrades at a moderate to rapid rate (its half-life is measured in days to weeks). The small amounts of DEET retained in air are subject to rapid photo-oxidation via hydroxyl radical-mediated degradation or, if in droplet form, gravitational settling to soil or water. DEET does not interfere with ozone formation in the upper atmosphere. The bioaccumulation potential of DEET is low; it is neither a persistent, bioaccumulative toxicant nor a persistent organic pollutant. Among aquatic species, acute effect concentrations range between 4 and 388 mg/L. The chronic no-observed effect concentrations (NOEC) for daphnids and green algae range from approximately 0.5 to 24 mg/L. Measured concentrations of DEET in surface waters are several hundreds to thousands of times lower than the lowest NOEC measured, and thus the probability for adverse effects to environmental species is low. A separate paper by Aronson et al. (this issue) supports this conclusion by quantitatively exploring the risks to the aquatic environment using a combination of monitoring data and exposure modeling.


Selective synchronization of Tetrahymena pyriformis cell populations and cell growth kinetics during the cell cycle.
A selection synchronization technique based on ingestion of tantalum particles has been applied to obtain synchronized cultures of the filter feeding ciliate Tetrahymena pyriformis. Cell concentrations and cell volume distributions of synchronized cell populations have been monitored for more than four average generation times. A simple curve-fitting method has been used to decompose the cell volume distributions of a synchronous population into two populations representing cells before and after cell division. In this way, the time course of the growth of an initially synchronous culture is decomposed into the growth of successive generations. The data indicate that at any given time only two generations of cells are present in significant numbers. The measured cell volume distributions show that T. pyriformis has a complicated growth pattern during the cell cycle. Newborn T. pyriformis cells do not grow significantly at the beginning of the cell cycle. After the nongrowing stage, cells start growing in a possibly exponential rate before cells enter into a second nongrowing stage. The second nongrowing stage lasts until cell division. The presented data demonstrate that growing cell populations can be viewed as the composite of cells belonging to different generations. This concept has important implications for solving corpuscular models of cell growth.


Poisson property of the occurrence of flip-flops in a model membrane.
How do lipid molecules in membranes perform a flip-flop? The flip-flops of lipid molecules play a crucial role in the formation and flexibility of membranes. However, little has been determined about the behavior of flip-flops, either experimentally, or in molecular dynamics simulations. Here, we provide numerical results of the flip-flops of model lipid molecules in a model membrane and investigate the statistical properties, using millisecond-order coarse-grained molecular simulations (dissipative particle dynamics). We find that there are three different ways of flip-flops, which can be clearly characterized by their paths on the free energy surface. Furthermore, we found that the probability of the number of the flip-flops is well fitted by the Poisson distribution, and the probability density function for the inter-occurrence times of flip-flops coincides with that of the forward recurrence times. These results indicate that the occurrence of flip-flops is a Poisson process, which will play an important role in the flexibilities of membranes.


Bio-inspired design of a magnetically active trilayered scaffold for cartilage tissue engineering.
An important topic in cartilage tissue engineering is the development of biomimetic scaffolds which mimic the depth-dependent material properties of the native tissue. We describe an advanced trilayered nanocomposite hydrogel (ferrogel) with a gradient in compressive modulus from the top to the bottom layers (p < 0.05) of the construct. Further, the scaffold was able to respond to remote external stimulation, exhibiting an elastic, depth-dependent strain gradient. When bovine chondrocytes were seeded into the ferrogels and cultured for up to 14 days, there was good cell viability and a biochemical gradient was measured with sulphated glycosaminoglycan increasing with depth from the surface. This novel construct provides tremendous scope for tailoring location-specific cartilage replacement tissue; by varying the density of magnetic nanoparticles, concentration of base hydrogel and number of cells, physiologically relevant depth-dependent gradients may be attained. © 2015 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.


Visual capture and understanding of hand pointing actions in a 3-D environment.
We present a nonintrusive system based on computer vision for human-computer interaction in three-dimensional (3-D) environments controlled by hand pointing gestures. Users are allowed to walk around in a room and manipulate information displayed on its walls by using their own hands as pointing devices. Once captured and tracked in real-time using stereo vision, hand pointing gestures are remapped onto the current point of interest, thus reproducing in an advanced interaction scenario the "drag and click" behavior of traditional mice. The system, called PointAt (patent pending), enjoys a careful modeling of both user and optical subsystem, and visual algorithms for self-calibration and adaptation to both user peculiarities and environmental changes. The concluding sections provide an insight into system characteristics, performance, and relevance for real applications.


Reading retention and transfer in TMR students.
Twenty-one TMR students at two schools completed 2 years of reading instruction using a whole-word approach. Students were pretested and posttested both years on two word lists; one list was made up of words included in the reading program, the other of words not included. The former list was used to assess word acquisition and retention, the latter to assess transfer. A one-way repeated measures analysis of variance indicated a statistically significant increase in words recognized. By the close of the second year, the average student had completed 100 lessons and had learned 41 words. Students retained most of the words they had learned over the 3-month summer vacation. A separate one-way repeated measures analysis indicated statistically significant transfer to untaught words. The authors concluded that TMR students can profit from reading instruction.


Risk factors and rates of bone flap resorption in pediatric patients after decompressive craniectomy for traumatic brain injury.
Decompressive craniectomy with subsequent autologous cranioplasty, or the replacement of the native bone flap, is often used for pediatric patients with traumatic brain injury (TBI) who have a mass lesion and intractable intracranial hypertension. Bone flap resorption is common after bone flap replacement, necessitating additional surgery. The authors reviewed their large database of pediatric patients with TBI who underwent decompressive craniectomy followed by bone flap replacement to determine the rate of bone flap resorption and identify associated risk factors. A retrospective cohort chart review was performed to identify long-term survivors who underwent decompressive craniectomy for severe TBI with bone flap replacement from January 1, 1996, to December 31, 2011. The risk factors investigated in a univariate statistical analysis were age, sex, underlying parenchymal contusion, Glasgow Coma Scale score on arrival, comminuted skull fracture, posttraumatic hydrocephalus, bone flap wound infection, and freezer time (the amount of time the bone flap was stored in the freezer before replacement). A multivariate logistic regression model was then used to determine which of these were independent risk factors for bone flap resorption. Bone flap replacement was performed at an average of 2.1 months after decompressive craniectomy. Of the 54 patients identified (35 boys, 19 girls; mean age 6.2 years), 27 (50.0%) experienced bone flap resorption after an average of 4.8 months. Underlying parenchymal contusion, comminuted skull fracture, age ≤ 2.5 years, and posttraumatic hydrocephalus were significant, or nearly significant, on univariate analysis. Multivariate analysis identified underlying contusion (p = 0.004, OR 34.4, 95% CI 3.0-392.7), comminuted skull fractures (p = 0.046, OR 8.5, 95% CI 1.0-69.6), posttraumatic hydrocephalus (p = 0.005, OR 35.9, 95% CI 2.9-436.6), and age ≤ 2.5 years old (p = 0.01, OR 23.1, 95% CI 2.1-257.7) as independent risk factors for bone flap resorption. After decompressive craniectomy for pediatric TBI, half of the patients (50%) who underwent bone flap replacement experienced resorption. Multivariate analysis indicated young age (≤ 2.5 years), hydrocephalus, underlying contusion as opposed to a hemispheric acute subdural hematoma, and a comminuted skull fracture were all independent risk factors for bone flap resorption. Freezer time was not found to be associated with bone flap resorption.


New onset atrial fibrillation developing in medical inpatients.
The outcome of patients who develop new onset atrial fibrillation (AF) after admission to an Internal Medicine service for acute medical illnesses is unknown. In a retrospective review, we compared patients in the study group: patients who were admitted to hospital for acute medical illnesses and subsequently developed new onset AF during hospitalization, with a control group 1: patients whose admitting diagnosis was new onset AF and a control group 2: patients who were admitted for acute medical illnesses and never developed AF. We analyzed clinical characteristics and all-cause mortality rate during the first 30 days, 6 months, and 1 year after admission. The 1-year mortality rates in study group were significantly higher than control group 1 (62% versus 8%, P < 0.001) and control group 2 (62% versus 29%, P < 0.05). These results suggest that AF and acute medical illness both are risk factors for increased mortality. The odds ratios were 4.05 (P = 0.023) and 18.33 (P = 0.001) for AF and acute medical illnesses, respectively, indicating that acute medical illness is the better predictor for mortality. Troponin I levels were elevated in 46% of patients in study group versus 12% in control group 1 and 42% in control group 2 (P < 0.05). Medical inpatients who develop new onset AF during hospitalization for acute medical illnesses have an increased mortality when compared with patients who were admitted solely for new onset AF. Acute medical illness rather than AF plays a more important role on the increased mortality in this subset of patient population.


Purification of human urinary prokallikrein. Identification of the site of activation by the metalloproteinase thermolysin.
Human urinary active kallikrein and prokallikrein were separated on DEAE-cellulose and octyl-Sepharose columns and both purified to homogeneity by affinity chromatography, gel filtration and hydrophobic h.p.l.c. Prokallikrein was monitored during purification by trypsin activation followed by determination of both amidase and kininogenase activity. After trypsin activation, purified prokallikrein had a specific kininogenase activity of 39.4 micrograms of bradykinin equivalent/min per mg and amidase activity of 16.5 mumol/min per mg with D-Val-Leu-Arg-7-amino-4-trifluoromethylcoumarin. Purified active kallikrein had a specific activity of 47 micrograms of bradykinin/min per mg. The molecular mass of prokallikrein was 48 kDa on electrophoresis and 53 kDa on gel filtration whereas active kallikrein gave values of 46 kDa and 53 kDa respectively. Antisera to active and prokallikrein were obtained. In double immunodiffusion and immunoelectrophoresis, antiserum to active kallikrein reacted with active and pro-kallikrein. Antiserum to prokallikrein contained antibodies to determinants not found in active kallikrein, presumably due to the presence of the activation peptide in the proenzyme. Human prokallikrein can be activated by thermolysin, trypsin and human plasma kallikrein. Activation of 50% of the prokallikrein (1.35 microM) was achieved in 30 min with 25 nM-thermolysin, 78 nM-trypsin or 180 nM-human plasma kallikrein. Thus thermolysin was the most effective activator. Thermolysin activated prokallikrein by releasing active kallikrein with N-terminal Ile1-Val2. Thus human tissue (glandular) prokallikrein can be activated by two types of enzymes: serine proteinases, which cleave at the C-terminus of basic amino acids, and by a metalloproteinase that cleaves at the N-terminus of hydrophobic amino acids.


Chemically distinct compartments of the thalamic VPM nucleus in monkeys relay principal and spinal trigeminal pathways to different layers of the somatosensory cortex.
The ventral posteromedial nucleus (VPM) of the monkey thalamus was investigated with combined immunocytochemical, histochemical, and connection-tracing techniques. Injections of anterogradely transported tracers were placed selectively in the caudal nucleus of the spinal trigeminal nuclear complex, and retrogradely transported horseradish peroxidase (HRP) or fluorescent dyes were placed on the surface or into the depths of defined parts of the trigeminal representation in the first somatic sensory area (SI) of the cerebral cortex. The results are correlated with those of the preceding paper (Rausell and Jones, 1991), which demonstrated the presence of 2 domains in the nucleus on the basis of different patterns of cytochrome oxidase (CO) staining and calcium-binding protein immunoreactivity. The cells of the CO-defined rod and matrix domains receive inputs from different components of the trigeminal afferent system and project to different layers of SI. The large- and medium-sized relay cells of the CO-rich rods, which are immunoreactive for parvalbumin, all project to middle layers of SI. The small relay cells of the weakly-stained CO-matrix, surrounding and intervening between the rods, are immunoreactive for 28-kDa calbindin and project to superficial layers (I and II) of SI. Anterograde tracing studies reveal that the rod domain in VPM is innervated by fibers arising in the contra- and ipsilateral principal trigeminal nucleus, while the matrix domain (and calbindin-positive domains in adjacent nuclei) are innervated by fibers arising in the caudal nucleus of the spinal trigeminal complex. These results demonstrate the modularity and parallel streaming of the functional components of the trigeminal part of the somatic sensory system and suggest that lemniscal and nonlemniscal elements of the system gain access by separate routes to different layers of the SI cortex.


Technological interventions enhancing curcumin bioavailability in wound healing therapeutics.
Wound healing has been a challenge in the medical field. Tremendous research has been carried to expedite wound healing by fabricating various formulations, some of which are now commercially available. However, owing to their natural source, people have been attracted to advanced formulations with herbal components. Among various herbs, curcumin has been a center of attraction from ancient times for its healing properties due to its multiple therapeutic effects, including antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, neuroprotective, and radioprotective properties. However, curcumin has a low water solubility and rapidly degrades into inactive metabolites, which limits its therapeutic efficacy. Henceforth, a carrier system is needed to carry curcumin, guard it against degradation, and keep its bioavailability and effectiveness. Different formulations with curcumin have been synthesized and exist in the form of various synthetic and natural materials, including nanoparticles, hydrogels, scaffolds, films, fibers, and nanoemulgels, improving its bioavailability dramatically. This review discusses the advances in different types of curcumin-based formulations used in wound healing in recent time, concentrating on its mechanisms of action and discussing the updates at its application at several stages of the wound healing process.


Dactylosporangium luridum sp. nov., Dactylosporangium luteum sp. nov. and Dactylosporangium salmoneum sp. nov., nom. rev., isolated from soil.
Forty strains isolated from soil taken from a hay meadow were assigned to the genus Dactylosporangium on the basis of colonial properties. 16S rRNA gene sequence analysis showed that the isolates formed a group that was most closely related to the type strain of Dactylosporangium aurantiacum, but well separated from other Dactylosporangium type strains and from 'Dactylosporangium salmoneum' NRRL B-16294. Twelve of 13 representative isolates had identical 16S rRNA gene sequences and formed a subclade that was distinct from corresponding phyletic lines composed of the remaining isolate, strain BK63T, the 'D. salmoneum' strain and the type strains of recognized Dactylosporangium species. DNA-DNA relatedness data indicated that representatives of the multi-membered 16S rRNA gene subclade, isolate BK63T and the 'D. salmoneum' subclade formed distinct genomic species; all of these organisms had chemotaxonomic and morphological properties consistent with their classification in the genus Dactylosporangium. They were also distinguished from one another and from the type strains of recognized Dactylosporangium species based on a range of phenotypic properties. Combined genotypic and phenotypic data showed that isolate BK63T, isolates BK51T, BK53 and BK69, and strain NRRL B-16294T should be classified in the genus Dactylosporangium as representing novel species. The names proposed for these species are Dactylosporangium luridum sp. nov. (type strain BK63T =DSM 45324T =KACC 20933T =NRRL B-24775T), Dactylosporangium luteum sp. nov. (type strain BK51T =DSM 45323T =KACC 20899T =NRRL B-24774T) and Dactylosporangium salmoneum sp. nov., nom. rev. (type strain NRRL B-16294T =ATCC 31222T =DSM 43910T =JCM 3272T =NBRC 14103T).


A novel betaproteobacterial agent of gill epitheliocystis in seawater farmed Atlantic salmon (Salmo salar).
Epitheliocystis, a disease characterised by cytoplasmic bacterial inclusions (cysts) in the gill and less commonly skin epithelial cells, has been reported in many marine and freshwater fish species and may be associated with mortality. Previously, molecular and ultrastructural analyses have exclusively associated members of the Chlamydiae with such inclusions. Here we investigated a population of farmed Atlantic salmon from the west coast of Norway displaying gill epitheliocystis. Although 'Candidatus Piscichlamydia salmonis', previously reported to be present in such cysts, was detected by PCR in most of the gill samples analysed, this bacterium was found to be a rare member of the gill microbiota, and not associated with the observed cysts as demonstrated by fluorescence in situ hybridization assays. The application of a broad range 16 S rRNA targeted PCR assay instead identified a novel betaproteobacterium as an abundant member of the gill microbiota. Fluorescence in situ hybridization demonstrated that this bacterium, tentatively classified as 'Candidatus Branchiomonas cysticola', was the cyst-forming agent in these samples. While histology and ultrastructure of 'Ca. B. cysticola' cysts revealed forms similar to the reticulate and intermediate bodies described in earlier reports from salmon in seawater, no elementary bodies typical of the chlamydial developmental cycle were observed. In conclusion, this study identified a novel agent of epitheliocystis in sea-farmed Atlantic salmon and demonstrated that these cysts can be caused by bacteria phylogenetically distinct from the Chlamydiae.


Postprandial Plasma Phospholipids in Men Are Influenced by the Source of Dietary Fat.
Postprandial lipemia represents a risk factor for chronic diseases, including type 2 diabetes. Little is known about the effect of dietary fat on the plasma lipidome in the postprandial period. The objective of this study was to assess the effect of dairy fat and soy oil on circulating postprandial lipids in men. Men (40-60 y old, nonsmokers; n = 16) were randomly assigned in a crossover design to consume 2 breakfast meals of dairy-based or soy oil-based foods. The changes in the plasma lipidome during the 4-h postprandial period were analyzed with electrospray ionization tandem mass spectrometry and included 316 lipid species in 23 classes and subclasses, representing sphingolipids, phospholipids, glycerolipids, and sterols. Nonparametric Friedman tests showed significant changes in multiple plasma lipid classes, subclasses, and species in the postprandial period after both dairy and soy meals. No difference was found in triglyceridemia after each meal. However, 6 endogenous lipid classes increased after dairy but decreased after soy (P < 0.05), including ether-linked phospholipids and plasmalogens and sphingomyelin (not present in soy), dihexosylceramide, and GM3 ganglioside. Phosphatidylcholine and phosphatidylinositol were not affected by the soy meal but were significantly elevated after the dairy meal (8.3% and 16%, respectively; P < 0.05). The changes in postprandial plasma phospholipids in men relate to the diet composition and the relative size of the endogenous phospholipid pools. Despite similar lipemic responses as measured by changes in triglyceride concentrations, the differential responses to dairy and soy meals derived through lipidomic analysis of phospholipids suggest differences in the metabolism of soybean oil and dairy fat. The increased concentrations of plasmalogens, with potential antioxidant capacity, in the postprandial period after dairy but not soy meals may represent a further important difference in the response to these sources of fat. The trial was registered at www.anzctr.org.au as ACTRN12610000562077.


Pathologic prostate cancer characteristics in patients eligible for active surveillance: a head-to-head comparison of contemporary protocols.
Although the rationale for active surveillance (AS) in patients with low-risk prostate cancer is well established, eligibility criteria vary significantly across different programs. To compare the ability of contemporary AS criteria to identify patients with certain pathologic tumor features based on the results of an extended transrectal prostate biopsy. The study cohort included 391 radical prostatectomy patients who had prostate cancer with Gleason scores ≤ 6 on transrectal biopsy with ≥ 10 cores. Radical prostatectomy without neoadjuvant treatment. We identified patients who fulfilled the inclusion criteria of five AS protocols including those of Epstein, Memorial Sloan-Kettering Cancer Center, Prostate Cancer Research International: Active Surveillance (PRIAS), University of California, San Francisco, and University of Miami (UM). We evaluated the ability of these criteria to predict three pathologic end points: insignificant disease defined using a classical and updated formulation, and organ-confined Gleason ≤ 6 prostate cancer. Measures of diagnostic accuracy and areas under the receiver operating curve were calculated for each protocol and compared. A total of 75% of the patients met the inclusion criteria of at least one protocol; 23% were eligible for AS by all studied criteria. The PRIAS and UM criteria had the best balance between sensitivity and specificity for both definitions of insignificant prostate cancer and a higher discriminative ability for the end points than any criteria including patients with two or more positive cores. The Epstein criteria demonstrated high specificity but low sensitivity for all pathologic end points, and therefore the discriminative ability was not superior to those of other protocols. Significant variations exist in the ability of contemporary AS criteria to predict pathologically insignificant prostate cancer at radical prostatectomy. These differences should be taken into account when making treatment choices in patients with low-risk prostate cancer.


Pharmacokinetic-pharmacodynamic analysis of vismodegib in preclinical models of mutational and ligand-dependent Hedgehog pathway activation.
Vismodegib (GDC-0449) is a potent and selective inhibitor of the Hedgehog (Hh) pathway that shows antitumor activity in preclinical models driven by mutational or ligand-dependent activation of the Hh pathway. We wished to characterize the pharmacokinetic-pharmacodynamic (PK/PD) relationship of vismodegib in both model systems to guide optimal dose and schedule for vismodegib in the clinic. Preclinical efficacy and PK/PD studies were carried out with vismodegib in a Ptch(+/-) allograft model of medulloblastoma exhibiting mutational activation of the Hh pathway and patient-derived colorectal cancer (CRC) xenograft models exhibiting ligand-dependent pathway activation. Inhibition of the hedgehog pathway was related to vismodegib levels in plasma and to antitumor efficacy using an integrated population-based PK/PD model. Oral dosing of vismodegib caused tumor regressions in the Ptch(+/-) allograft model of medulloblastoma at doses ≥25 mg/kg and tumor growth inhibition at doses up to 92 mg/kg dosed twice daily in two ligand-dependent CRC models, D5123, and 1040830. Analysis of Hh pathway activity and PK/PD modeling reveals that vismodegib inhibits Gli1 with a similar IC(50) in both the medulloblastoma and D5123 models (0.165 μmol/L ±11.5% and 0.267 μmol/L ±4.83%, respectively). Pathway modulation was linked to efficacy using an integrated PK/PD model revealing a steep relationship where > 50% of the activity of vismodegib is associated with >80% repression of the Hh pathway. These results suggest that even small reductions in vismodegib exposure can lead to large changes in antitumor activity and will help guide proper dose selection for vismodegib in the clinic.


Interface pinning of immiscible gravity-exchange flows in porous media.
We study the gravity-exchange flow of two immiscible fluids in a porous medium and show that, in contrast with the miscible case, a portion of the initial interface remains pinned at all times. We elucidate, by means of micromodel experiments, the pore-level mechanism responsible for capillary pinning at the macroscale. We propose a sharp-interface gravity-current model that incorporates capillarity and quantitatively explains the experimental observations, including the x~t(1/2) spreading behavior at intermediate times and the fact that capillarity stops a finite-release current. Our theory and experiments suggest that capillary pinning is potentially an important, yet unexplored, trapping mechanism during CO(2) sequestration in deep saline aquifers.


Toward a clinical practice guide in pharmacogenomics testing for functional polymorphisms of drug-metabolizing enzymes. Gene/drug pairs and barriers perceived in Spain.
The development of clinical practice recommendations or guidelines for the clinical use of biomarkers is an issue of great importance with regard to adverse drug reactions. The potential of pharmacogenomic biomarkers has been extensively investigated in recent years. However, several barriers to implementing the use of pharmacogenomics testing exist. We conducted a survey among members of the Spanish Societies of Pharmacology and Clinical Pharmacology to obtain information about the perception of such barriers and to compare the perceptions of participants about the relative importance of major gene/drug pairs. Of 11 potential barriers, the highest importance was attributed to lack of institutional support for pharmacogenomics testing, and to the issues related to the lack of guidelines. Of the proposed gene/drug pairs the highest importance was assigned to HLA-B/abacavir, UGT1A1/irinotecan, and CYP2D6/tamoxifen. In this perspective article, we compare the relative importance of 29 gene/drug pairs in the Spanish study with that of the same pairs in the American Society for Clinical Pharmacology and Therapeutics study, and we provide suggestions and areas of focus to develop a guide for clinical practice in pharmacogenomics testing.


Activation of mineralocorticoid receptors by exogenous glucocorticoids and the development of cardiovascular inflammatory responses in adrenalectomized rats.
Activation of the mineralocorticoid receptor (MR) in the context of a high salt intake produces cardiovascular inflammation plus cardiac fibrosis and failure. Inactivation of vascular 11beta-hydroxysteroid dehydrogenase type 2 activity in intact animals by carbenoxolone (CBX) produces a similar pathology, presumably reflecting coronary vascular MR activation by endogenous glucocorticoids. To test this hypothesis, we have used adrenalectomized rats, without endogenous corticosteroids, and examined the consequences of corticosterone (CORT) replacement on a series of cardiovascular disease parameters. Uninephrectomized adrenalectomized Sprague Dawley rats given 1% NaCl/0.3% KCl to drink were treated for 8 d as follows: control; 20 mg deoxycorticosterone (DOC); 2 mg/d CORT; 2.5 mg/d CBX; CORT plus CBX (CORT/CBX); and CORT/CBX plus 100 mg/kg.d eplerenone. Markers of cardiac oxidative stress (p22(phox) and NOX4 mRNA) were up-regulated in the DOC and CORT/CBX groups; in contrast, inflammatory cell infiltration was increased and endothelial nitric oxide synthase down-regulated by CORT as well as by DOC and CORT/CBX. In the kidney, connective tissue growth factor mRNA levels were increased by DOC and CORT/CBX; in contrast, DOC had no effect on mRNA levels for channel inducing factor or endothelin 3, which were elevated only by CORT/CBX. All changes noted were reversed by eplerenone. Rats given 10-fold lower CORT (0.2 mg/d) with or without CBX showed no change in any parameter. These results suggest that there exist distinct but overlapping ligand-specific MR-mediated tissue responses to a classic mineralocorticoid (DOC) and to the glucocorticoid CORT, in the presence and absence of CBX to block vascular 11beta-hydroxysteroid dehydrogenase type 2.


Alpha Oscillations Modulate Preparatory Activity in Marmoset Area 8Ad.
Cognitive control often requires suppression of prepotent stimulus-driven responses in favor of less potent alternatives. Suppression of prepotent saccades has been shown to require proactive inhibition in the frontoparietal saccade network. Electrophysiological evidence in macaque monkeys has revealed neural correlates of such inhibition in this network; however, the interlaminar instantiation of inhibitory processes remains poorly understood because these areas lie deep within sulci in macaques, rendering them inaccessible to laminar recordings. Here, we addressed this gap by exploiting the mostly lissencephalic cortex of the common marmoset (Callithrix jacchus). We inserted linear electrode arrays into areas 8Ad-the putative marmoset frontal eye field-and the lateral intraparietal area of two male marmosets and recorded neural activity during performance of a task comprised of alternating blocks of trials requiring a saccade either toward a large, high-luminance stimulus or the inhibition of this prepotent response in favor of a saccade toward a small, low-luminance stimulus. We observed prominent task-dependent activity in both alpha/gamma bands of the LFP and discharge rates of single neurons in area 8Ad during a prestimulus task epoch in which the animals had been instructed which of these two tasks to perform but before peripheral stimulus onset. These data are consistent with a model in which rhythmic alpha-band activity in deeper layers inhibits spiking in upper layers to support proactive inhibitory saccade control.SIGNIFICANCE STATEMENT Failures to inhibit automatic saccadic responses are a hallmark of many neuropsychiatric disorders, but how this process is implemented across the cortical layers in the frontoparietal saccade network remains unknown because many of the areas are inaccessible to laminar recordings in macaques. Here, we investigated laminar neural activity in marmoset monkeys, which have a smooth cortex. Monkeys were required either to generate or inhibit a prepotent saccade response. In area 8Ad, the putative frontal eye field in marmosets, rhythmic alpha-band activity (9-14 Hz) was higher in deeper layers and spiking activity was lower in upper layers when the animals were instructed to suppress a saccade toward a peripheral stimulus. Reduced alpha power during task preparation may be the underlying common neural basis of a saccade suppression deficit.


Identifying Language for People on the Autism Spectrum: A Scoping Review.
Person-first language is considered a central component to recovery oriented person-centred care; however, there is a growing adoption of identify-first language among autistic advocates. Mental health nurses require awareness of critical autism issues given the high prevalence of comorbid psychopathology. This scoping review of literature from 2010 to 2018 regarding identifying language for people on the autism spectrum identified a paucity of research that systematically explored and considered antagonisms, representation, and potential consequences of either of the current modes of identifying language becoming dominant. Mental health nurses should appreciate the complexity within identifying language and adopt context dependent language.


Editorial: in silico drug design and medicinal chemistry).
Medicinal chemistry is not limited to molecules, their structures and design but also highly cohesive to pharmacological activities. The potency of a molecule varies by its structure. Hence structural activity relationship is the sub-branch which deals with the estimation of ability of a molecule in depicting any pharmacological activity. In silico drug design is a novel technique which is employed in designing a molecule by using computer aided software's and bringing a superior and potent molecule. In recent years, in silico drug design has been merged with medicinal chemistry especially by the techniques like ligand based strategy to isolate the required structures. By such strategic techniques, there are high chances of delivering high throughput screening which involves of screening large number of molecules in a very less time. Involvement of such techniques would be a boon for development of new drug entity as it can aid in development of newer, safe, effective and potent drug molecules. Hence, the present issue is aimed to emphasize the cohesion between in silico drug design and it significance in medicinal chemistry. The articles which would be published will mainly focus on the role of in silico drug design techniques in the development of molecules to target various disease and disorders. Molecules can from natural/ synthetic/semi synthetic origin. Articles will be a treasure box consisting of employment of computational methods for unprecedented molecules. The issue will be sure an endorsement for international readership and researchers.


Role of brain dopamine systems in the development of hypertension in the spontaneously hypertensive rat.
We studied the role of central dopamine in the development of hypertension. Earlier work had shown that depletion of brain dopamine can inhibit the age-related rise in blood pressure in spontaneously hypertensive rats (SHR). In an open-field test, locomotor activity of Wistar-Kyoto controls was inhibited by haloperidol, apomorphine and sulpiride, but these drugs had less effect in SHR. The stimulation-evoked release of [3H]-dopamine from slices of the striatum of SHR was smaller than that from slices of WKY. The inhibition of the stimulation-evoked release of [3H]-dopamine by quinpirole was greater in SHR than in WKY. The results from the lesion experiments and from the behavioural activity studies would suggest an enhanced release of central dopamine in SHR, which might contribute to the development of hypertension in these animals. However, the in vitro release experiments (and subsequent in vivo microdialysis experiments) do not support such an enhanced release but rather showed decreased release of striatal dopamine in SHR.


Lithographically defined porous Ni-carbon nanocomposite supercapacitors.
Ni was deposited onto lithographically-defined conductive three dimensional carbon networks to form asymmetric pseudo-capacitive electrodes. A real capacity of above 500 mF cm(-2), or specific capacitance of ∼2100 F g(-1) near the theoretical value, has been achieved. After a rapid thermal annealing process, amorphous carbon was partially converted into multilayer graphene depending on the annealing temperature and time duration. These annealed Ni-graphene composite structures exhibit enhanced charge transport kinetics relative to un-annealed Ni-carbon scaffolds indicated by a reduction in peak separation from 0.84 V to 0.29 V at a scan rate of 1000 mV s(-1).


Neurologic complications and outcomes of infective endocarditis in critically ill patients: the ENDOcardite en REAnimation prospective multicenter study.
To describe the clinical spectrum of infective endocarditis in critically ill patients and assess the impact of neurologic complications on outcomes. Prospective multicenter observational study conducted from April 2007 to October 2008. Thirty-three intensive care units in 23 university-affiliated and 10 general French hospitals. Two hundred twenty-five patients with definite IE were studied. Factors associated with neurologic complications and predictors of 3-month mortality were identified by logistic regression analysis. Functional outcomes of patients with neurologic complications were evaluated with the modified Rankin Scale. None. Among 198 patients with definite left-sided infective endocarditis, 108 (55%) experienced at least one neurologic complication. These complications were ischemic stroke (n = 79), cerebral hemorrhage (n = 53), meningitis or meningeal reaction (n = 41), brain abscess (n = 14), and mycotic aneurysm (n = 10). Factors independently associated with neurologic complications were (subhazard ratio [95% confidence interval]): Staphylococcus aureus infective endocarditis (1.45 [1.02-2.05]), mitral valve infective endocarditis (1.54 [1.07-2.21]), and nonneurologic embolic events (1.51 [1.09-2.09]). In contrast, health care-associated infective endocarditis had a protective effect (0.46 [0.27-0.77]). Multivariate analysis identified three variables associated with 3-month mortality (odds ratio [95% confidence interval]): neurologic failure, as defined as a Glasgow Coma Scale <10 (7.41 [2.89-18.96]), S. aureus infective endocarditis (3.26 [1.53-6.94]), and severe comorbidities before admission as defined as a Charlson score >2 (3.16 [1.47-6.77]). Among the 106 patients with neurologic complications assessed at follow-up (3.9 [3-8.5] months), 31 (29%) had a modified Rankin Scale score ≤3 (ability to walk without assistance), nine (9%) a modified Rankin Scale score of 4 or 5 (severe disability), and 66 (62%) a modified Rankin Scale score of 6 (death). Neurologic events are the most frequent complications in infective endocarditis patients requiring intensive care unit admission. They contribute to a severe prognosis, leaving less than one-third of patients alive with functional independence. Neurologic failure at intensive care unit admission represents a major determinant of mortality regardless of the underlying neurologic complication.


Pneumostomy: an operative proposal for the treatment of severe diffuse pulmonary emphysema.
to evaluate a new operative technique for the treatment of advanced pulmonary emphysema. we conducted a prospective analysis of nine patients with severe pulmonary emphysema submitted to pneumostomy. The procedure was performed under local anesthesia, in the anterior thoracic wall, hemiclavicular line, in the second intercostal space, through an anterior thoracotomy of 5cm for access to the upper lobe, whose anterior segment was pinched and fixed to the parietal pleura. We carried out the pneumostomy with electrocautery and blunt insertion of an intrapulmonary drain. To assess the procedure, we performed pulmonary function tests, imaging tests, six-minute walk test, and applied quality of life questionnaires, all measured preoperatively and 30 days after the procedure. no deaths occurred related to the procedure. Imaging studies showed a decrease in lung volume. The pulmonary function showed a significant reduction in the residual volume. The six-minute walk test showed an increase in the distance covered in the postoperative period. There was significant improvement of the quality of life as demonstrated through questionnaires Medical Outcomes Study 36 Item Short-Form Health Survey (SF-36), Saint-George Respiratory Questionnaire (SGRQ), Medical Research Council scale (MRC), and Eastern Cooperative Oncology Group Performance status (ECOG). the proposed technique is feasible, safe, easy to perform and to maintain.


Method of paired transforms for reconstruction of images from projections: discrete model.
In this paper, an effective method of discrete image reconstruction from its projections is introduced. The method is based on the vector and paired representations of the two-dimensional (2D) image with respect to the 2D discrete Fourier transform. Such representations yield algorithms for image reconstruction by a minimal number of attenuation measurements in certain projections. The proposed algorithms are described in detail for an N x N image, when N = 2(r), r > 1. The inverse formulas for image reconstruction are given. The efficiency of the algorithms is expressed in the fact that they require a minimal number of multiplications, or can be implemented without such at all. The problem of discrete image reconstruction is also considered in three-dimensional (3D) space, namely on the 3D torus, where the reconstruction is performed by means of the nonlinear projections that are integral over 3D spirals on the torus.


Mobilization of cellular calcium-45 and lead-210: effect of physiological stimuli.
Isolated rat hepatocytes in primary culture were used as a model system to evaluate the effects of selected hormones and culture conditions on the efflux of calcium-45 and lead-210 from cells labeled with these isotopes. Alpha-adrenergic stimuli, angiotensin, vasopressin, dibutyryl adenosine 3',5'-monophosphate, and reduced phosphate concentrations in the medium increased the efflux of calcium-45 and lead-210. Glucagon and insulin had no effect, but increased phosphate concentrations decreased the efflux of both isotopes. Experiments with hepatocytes cultured in a medium free of calcium and lead demonstrated that the increased efflux of calcium-45 and lead-210 induced by hormones was the result of mobilization of the ions from intracellular stores. The data indicate that the physiological stimuli that mobilized calcium ions also mobilized lead ions, and that the mobilized lead would be available to interact with calcium-mediated cell functions.