[Therapeutic recommendations. Secondary prevention of cerebral vascular accident].
The guidelines for secondary stroke prevention, graded following available scientific evidence, are presented. Stroke and TIA are defined and the indications for referral established. Basic assessment of stroke patients should include laboratory evaluation, ECG, brain CT, ultrasound examination of the extracranial vessels for events in the carotid distribution, and transthoracic or transesophageal echocardiogram if cardioembolism is suspected. The pharmacological and non-pharmacological reduction of blood pressure and serum cholesterol, stopping smoking and reducing alcohol intake are general measures recommended for secondary stroke prevention, together with healthier life-style changes (eating a Mediterranean type diet and performing regular moderate physical exercise). Concerning antithrombotic therapy, oral anticoagulants are recommended for patients with atrial fibrillation and other high to medium emboligenic cardiac risk conditions. Antiplatelet drugs are recommended for all other survivors of an ischemic cerebral event. Aspirin (75-325 mg/day) is the drug of choice. Alternative antiplatelet agents are clopidrogrel, ticlopidine, dipiridamol or triflusal. They can be used in patients with intolerance or contraindication to aspirin or in high-risk subjects. Endarterectomy of the symptomatic carotid is an additional procedure recommended for patients with ischemic stroke or TIA and carotid stenosis > 80% on the side of the symptomatic cerebral hemisphere.


Effects of galvanic vestibular stimulation during human walking.
1. To identify vestibular influences on human walking, galvanic vestibular stimulation was applied to normal adult subjects as they walked to a previously seen target. A transmastoidal step stimulus commenced as subjects started walking. With the eyes shut, the galvanic stimulus caused large turns towards the side with the anodal current. 2. Ability to perceive the trajectory of gait without visual cues was measured by guiding blindfolded subjects from one arbitrary point to another, either walking or seated in a wheelchair. On reaching a destination position and removing the blindfold, subjects pointed to indicate the starting position. Subjects made considerable errors in estimating the trajectory, but were equally accurate whether in the wheelchair or walking. 3. To determine the effects of vestibular stimulation on the perception of trajectory, the galvanic stimulus was applied to blindfolded subjects as they were guided from one point to another in the wheelchair. The vestibular stimulus produced an illusory shift in the trajectory travelled. This shift was towards the side with the cathode, i.e. in the opposite direction to the turn produced by the stimulus during walking. 4. We conclude that galvanic vestibular stimulation during walking causes subjects to turn from their planned trajectory. In part, this altered course may compensate for an altered perception of trajectory produced by the stimulus. However, altered perception of the vertical or the base of support, or direct vestibulo-fugal influences on the leg muscles could contribute to the changes in gait.


ZORRO: zirconium oxide resonators for all-in-one Raman and whispering-gallery-mode optical sensing.
We report the observation of whispering-gallery modes in 2 μm-sized SiO2/ZrO2 core/shell beads utilized as all-dielectric Raman enhancers. This allows us to achieve simultaneous optical and Raman ultrasensitive detection with a single spectral analysis. This opportunity opens exciting perspectives for the multimodal chemical sensing and fabrication of optical fiber devices.


Investigations on oxidative stress and therapeutical implications in dementia.
Alzheimer's disease (AD) is a progressive dementia affecting a large proportion of the aging population. The histopathological changes in AD include neuronal cell death and formation of amyloid plaques and neurofibrillary tangles (NFTs) NFTs are composed of hyperphosphorylated tau protein, and senile plaques contain aggregates of the beta-peptide. There is also evidence that brain tissue in patients with AD is exposed to oxidative stress during the course of the disease. Advanced glycation endproducts (AGEs), which are formed by a non-enzymatic reaction of glucose with long-lived protein deposits, are potentially toxic to the cell, are present in brain plaques in AD, and its extracellular accumulation in AD may be caused by an accelerated oxidation of glycated proteins. The microtubuli-associated protein tau is also subject to intracellular AGE formation. AGEs participate in neuronal death causing direct (chemical) radical production: Glycated proteins produce nearly 50-fold more radicals than non-glycated proteins, and indirect (cellular) radical production: Interaction of AGEs with cells increases oxidative stress. During aging cellular defence mechanisms weaken and the damages to cell constituents accumulate leading to loss of function and finally cell death. The development of drugs for the treatment of AD remains at a very unsatisfying state. However, pharmacological approaches which break the vicious cycles of oxidative stress and neurodegeneration offer new opportunities for the treatment of AD. Theses approaches include AGE-inhibitors, antioxidants, and anti-inflammatory substances, which prevent radical production. AGE inhibitors might be able to stop formation of AGE-modified beta-amyloid deposits, antioxidants are likely to scavenge intracellular and extracellular superoxide radicals and hydrogen peroxide before these radicals damage cell constituents or activate microglia, and anti-inflammatory drugs attenuating microglial radical and cytokine production.


Extracellular matrix and its receptors in Drosophila neural development.
Extracellular matrix (ECM) and matrix receptors are intimately involved in most biological processes. The ECM plays fundamental developmental and physiological roles in health and disease, including processes underlying the development, maintenance, and regeneration of the nervous system. To understand the principles of ECM-mediated functions in the nervous system, genetic model organisms like Drosophila provide simple, malleable, and powerful experimental platforms. This article provides an overview of ECM proteins and receptors in Drosophila. It then focuses on their roles during three progressive phases of neural development: (1) neural progenitor proliferation, (2) axonal growth and pathfinding, and (3) synapse formation and function. Each section highlights known ECM and ECM-receptor components and recent studies done in mutant conditions to reveal their in vivo functions, all illustrating the enormous opportunities provided when merging work on the nervous system with systematic research into ECM-related gene functions.


Love Wave Sensors with Silver Modified Polypyrrole Nanoparticles for VOCs Monitoring.
Love wave sensors with silver-modified polypyrrole nanoparticles are developed in this work. These systems prove functional at room temperature with enhanced response, sensitivity and response time, as compared to other state-of-the-art surface acoustic wave (SAW) sensors, towards volatile organic compounds (VOCs). Results demonstrate the monitoring of hundreds of ppb of compounds such as acetone, ethanol and toluene with low estimated limits of detection (~3 ppb for acetone). These results are attributed to the use of silver-modified polypyrrole as a second guiding/sensitive layer in the Love wave sensor structure, which provides further chemically active sites for the gas-solid interactions. The sensing of low VOCs concentrations by micro sensing elements as those presented here could be beneficial in future systems for air quality control, food quality control or disease diagnosis via exhaled breath as the limits of detection obtained are within those required in these applications.


Motor Evoked Potentials in Hereditary Spastic Paraplegia-A Systematic Review.
Background: Hereditary Spastic Paraplegia (HSP) is a slowly progressive neurodegenerative disorder with no disease modifying treatment. Potential therapeutic approaches are emerging and large-scale clinical drug trials for patients with HSP are imminent. A sensitive biomarker to measure the drug efficacy in these trials is required. Motor evoked potentials (MEPs) are a potential biomarker for HSP as they assess the central motor pathways and can be standardized with set protocols and guidelines. Objectives: We performed a systematic review to investigate the utility of MEPs as a diagnostic and disease severity biomarker for HSP. Search Methods: Systematic searches of PubMed, Embase, Medline, and Scopus were performed. Selection Criteria: Studies reporting on central motor conduction time measured with MEPs in adult and pediatric patients with HSP were included. We excluded studies in non-HSP patient cohorts, not in English, not original research, and unpublished journal articles. Data Collection and analysis: Search results were de-duplicated and screened according to the inclusion and exclusion criteria. The included papers were reviewed independently by two reviewers and data was collected on patient cohorts, test methods, results, and study quality. Results were analyzed using descriptive methods. Results: Of the 882 search results, 32 studies were included in the review. The most common finding was absent or prolonged lower limb (LL) central motor conduction time (CMCT) in patients with HSP (78% of patients studied). Quality assessment revealed variability in study methodology and reporting of results. Variations included patient cohorts of various genotypes as well as variations in equipment and techniques used. Aside from CMCT, none of the MEP parameter measures correlated with disease severity and many did not show significant difference between HSP patients and controls. Conclusion: Systematic review of MEP studies in HSP patient cohorts demonstrated mixed findings. Lower limb CMCT was the most promising parameter in terms of differentiating HSP patients from controls, with one study demonstrating a weak correlation with clinical disease severity. It is possible that the lack of consistency in study methodologies and small patient cohorts have contributed to the variable findings. A longitudinal study of MEPs in a large cohort of HSP patients with the same genotype will help clarify the utility of MEPs as a biomarker for disease severity and use in clinical trials.


Salivary flow rate in patients with schizophrenia on clozapine.
To assess the change in salivary flow rate in patients with schizophrenia on clozapine and whether the change in salivary flow rate was dose related. Twenty male inpatients with a diagnosis of schizophrenia according to the International Statistical Classification of Diseases, 10th Revision diagnostic criteria for research who were started on clozapine were recruited for the study. Unstimulated salivary flow rate was assessed at baseline and then weekly for 4 weeks using cotton swab method in 17 patients. Repeated-measures analysis of variance showed a significant increase in salivary flow rate over time (F [2.37/37.94] = 3.134, P = 0.047, Greenhouse-Geisser correction, eta = 0.16). Also, there was a significant increase in salivary flow rate between weeks 2 and 3 (P < 0.05). There was no correlation between salivary flow rate and mean clozapine dose. There was a significant increase in salivary flow rate from baseline after starting clozapine, with a significant increase from the second to the third week followed by a "plateau."


Video surveillance captures student hand hygiene behavior, reactivity to observation, and peer influence in Kenyan primary schools.
In-person structured observation is considered the best approach for measuring hand hygiene behavior, yet is expensive, time consuming, and may alter behavior. Video surveillance could be a useful tool for objectively monitoring hand hygiene behavior if validated against current methods. Student hand cleaning behavior was monitored with video surveillance and in-person structured observation, both simultaneously and separately, at four primary schools in urban Kenya over a study period of 8 weeks. Video surveillance and in-person observation captured similar rates of hand cleaning (absolute difference <5%, p = 0.74). Video surveillance documented higher hand cleaning rates (71%) when at least one other person was present at the hand cleaning station, compared to when a student was alone (48%; rate ratio = 1.14 [95% CI 1.01-1.28]). Students increased hand cleaning rates during simultaneous video and in-person monitoring as compared to single-method monitoring, suggesting reactivity to each method of monitoring. This trend was documented at schools receiving a handwashing with soap intervention, but not at schools receiving a sanitizer intervention. Video surveillance of hand hygiene behavior yields results comparable to in-person observation among schools in a resource-constrained setting. Video surveillance also has certain advantages over in-person observation, including rapid data processing and the capability to capture new behavioral insights. Peer influence can significantly improve student hand cleaning behavior and, when possible, should be exploited in the design and implementation of school hand hygiene programs.


Dynameomics: protein dynamics and unfolding across fold space.
All currently known structures of proteins together define 'protein fold space'. To increase the general understanding of protein dynamics and protein folding, we selected a set of 807 proteins and protein domains that represent 95% of the currently known autonomous folded domains present in globular proteins. Native state and unfolding simulations of these representatives are now complete and accessible via a novel database containing over 11 000 simulations. Because protein folding is a microscopically reversible process, these simulations effectively sample protein folding across all of protein fold space. Here, we give an overview of how the representative proteins were selected and how the simulations were performed and validated. We then provide examples of different types of analyses that can be performed across our large set of simulations, made possible by the database approach. We further show how the unfolding simulations can be used to compare unfolding of structural elements in isolation and in different structural contexts, using as an example a short, triple stranded β-sheet that forms the WW domain and is present in several larger unrelated proteins.


On the perceptual/motor dissociation: a review of concepts, theory, experimental paradigms and data interpretations.
With its roots in Ungerleider and Mishkin's (1982) uncovering of two distinct - ventral and dorsal - anatomical pathways for the processing of visual information, and boosted by Goodale and Milner's (1992; Milner and Goodale, 1995) behavioral study of patients with lesions of either of these pathways, the perception-action dissociation became a standard reference in the sensorimotor literature. Here we present briefly the anatomical, neuropsychological and, more extensively, the psychophysical evidence favoring such dissociation and pit it against counteracting evidence as well as against potential methodological and conceptual pitfalls. We also discuss classes of models accounting for a number of 'dissociation' results and conclude that the most general and parsimonious one posits the existence of one single processing stream that accumulates information up to a decision criterion modulated by stimulation conditions, response mode (motor vs. verbal/perceptual), task constraints (speeded vs. free time responses) and the nature of the task (detection, discrimination, temporal order judgment, etc.). The reviewed evidence is not meant to refute or validate the hypothesis of a perceptual-motor dissociation. Rather, its main objective is to show that, beyond its self-evidence, such dissociation is difficult if not impossible to test.


Piezosurgical osteotomy for harvesting intraoral block bone graft.
The use of ultrasonic vibrations for the cutting of bone was first introduced two decades ago. Piezoelectric surgery is a minimally invasive technique that lessens the risk of damage to surrounding soft tissues and important structures such as nerves, vessels, and mucosa. It also reduces damage to osteocytes and permits good survival of bony cells during harvesting of bone. Grafting with intraoral bone blocks is a good way to reconstruct severe horizontal and vertical bone resorption in future implants sites. The piezosurgery system creates an effective osteotomy with minimal or no trauma to soft tissue in contrast to conventional surgical burs or saws and minimizes a patient's psychological stress and fear during osteotomy under local anesthesia. The purpose of this article is to describe the harvesting of intraoral bone blocks using the piezoelectric surgery device.


Linking local knowledge with global action: examining the Global Fund to Fight AIDS, Tuberculosis and Malaria through a knowledge system lens.
New global public health institutions are increasingly emphasizing transparency in decision-making, developing-country ownership of projects and programmes, and merit- and performance-based funding. Such principles imply an institutional response to the challenge of bridging the "know-do gap", by basing decisions explicitly on results, evidence and best practice. Using a knowledge systems framework, we examine how the Global Fund to Fight AIDS, Tuberculosis and Malaria has affected the ways in which knowledge is used in efforts to combat these three diseases. We outline the formal knowledge system embedded in current rules and practices associated with the Global Fund's application process, and give three examples that illustrate the complexity of the knowledge system in action: human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) policy in China; successful applications from Haiti; and responses to changing research on malaria. These examples show that the Global Fund has created strong incentives for knowledge to flow to local implementers, but with little encouragement and few structures for the potentially valuable lessons from implementation to flow back to global best practice or research-based knowledge. The Global Fund could play an influential role in fostering much-needed learning from implementation. We suggest that three initial steps are required to start this process: acknowledging shared responsibility for learning across the knowledge system; analysing the Global Fund's existing data (and refining data collection over time); and supporting recipients and technical partners to invest resources in linking implementation with best practice and research.


Radiological Management of Angiographically Negative, Spontaneous Intracranial Subarachnoid Hemorrhage: A Multicenter Study of Utilization and Diagnostic Yield.
The optimal diagnostic evaluation for patients with angiographically negative subarachnoid hemorrhage (AN-SAH) remains controversial. To assess the utilization rate and diagnostic yield of imaging tests routinely obtained in identifying a structural cause for AN-SAH. In this retrospective multicenter study, consecutive adult patients admitted with nontraumatic, AN-SAH between 01/2010 and 12/2015 were included. Patients with intraparenchymal, subdural, or epidural hematomas in addition to SAH were excluded. Outcomes studied included utilization rate, diagnostic yield, and median time from admission for the following imaging tests: initial computed tomography angiography (CTA) and digital subtraction angiography (DSA), brain and cervical spine magnetic resonance imaging (MRI), and any repeat DSA or CTA performed either during initial admission or at long-term follow-up. A total of 752 patients were included (mean age, 53 yr; 54% male). Initial CTA and DSA were performed in 89% and 100% of patients, respectively. Brain MRI was performed in 75% of patients and was positive in 0.7% of cases. Cervical spine MRI was performed in 61% of patients and was positive in 0.2% of cases. Repeat, same-admission follow-up DSA and CTA were performed in 48% and 51% of patients and were positive in 3.3% and 1% of cases, respectively. Delayed follow-up DSA and CTA after discharge were performed in 26% and 7% of patients and were positive in 2% and 3.7% of cases, respectively, all with negative prior imaging studies. Cervical spine and brain MRI have extremely low diagnostic yield, both are commonly utilized in patients with AN-SAH; while repeat DSA and CTA are utilized less commonly and have slightly higher diagnostic yield.


Opportunities for system level improvement in antibiotic use across the surgical pathway.
Optimizing antibiotic prescribing across the surgical pathway (before, during, and after surgery) is a key aspect of tackling important drivers of antimicrobial resistance and simultaneously decreasing the burden of infection at the global level. In the UK alone, 10 million patients undergo surgery every year, which is equivalent to 60% of the annual hospital admissions having a surgical intervention. The overwhelming majority of surgical procedures require effectively limited delivery of antibiotic prophylaxis to prevent infections. Evidence from around the world indicates that antibiotics for surgical prophylaxis are administered ineffectively, or are extended for an inappropriate duration of time postoperatively. Ineffective antibiotic prophylaxis can contribute to the development of surgical site infections (SSIs), which represent a significant global burden of disease. The World Health Organization estimates SSI rates of up to 50% in postoperative surgical patients (depending on the type of surgery), with a particular problem in low- and middle-income countries, where SSIs are the most frequently reported healthcare-associated infections. Across European hospitals, SSIs alone comprise 19.6% of all healthcare-acquired infections. Much of the scientific research in infection management in surgery is related to infection prevention and control in the operating room, surgical prophylaxis, and the management of SSIs, with many studies focusing on infection within the 30-day postoperative period. However it is important to note that SSIs represent only one of the many types of infection that can occur postoperatively. This article provides an overview of the surgical pathway and considers infection management and antibiotic prescribing at each step of the pathway. The aim was to identify the implications for research and opportunities for system improvement.


Definition of a critical region on chromosome 18 for congenital aural atresia by arrayCGH.
Deletions of the long arm of chromosome 18 occur in approximately 1 in 10,000 live births. Congenital aural atresia (CAA), or narrow external auditory canals, occurs in approximately 66% of all patients who have a terminal deletion 18q. The present report describes a series of 20 patients with CAA, of whom 18 had microscopically visible 18q deletions. The extent and nature of the chromosome-18 deletions were studied in detail by array-based comparative genomic hybridization (arrayCGH). High-resolution chromosome-18 profiles were obtained for all patients, and a critical region of 5 Mb that was deleted in all patients with CAA could be defined on 18q22.3-18q23. Therefore, this region can be considered as a candidate region for aural atresia. The array-based high-resolution copy-number screening enabled a refined cytogenetic diagnosis in 12 patients. Our approach appeared to be applicable to the detection of genetic mosaicisms and, in particular, to a detailed delineation of ring chromosomes. This study clearly demonstrates the power of the arrayCGH technology in high-resolution molecular karyotyping. Deletion and amplification mapping can now be performed at the submicroscopic level and will allow high-throughput definition of genomic regions harboring disease genes.


Inhibition of antithrombin by hyaluronic acid may be involved in the pathogenesis of rheumatoid arthritis.
Thrombin is a key factor in the stimulation of fibrin deposition, angiogenesis, proinflammatory processes, and proliferation of fibroblast-like cells. Abnormalities in these processes are primary features of rheumatoid arthritis (RA) in synovial tissues. Tissue destruction in joints causes the accumulation of large quantities of free hyaluronic acid (HA) in RA synovial fluid. The present study was conducted to investigate the effects of HA and several other glycosaminoglycans on antithrombin, a plasma inhibitor of thrombin. Various glycosaminoglycans, including HA, chondroitin sulfate, keratan sulfate, heparin, and heparan, were incubated with human antithrombin III in vitro. The residual activity of antithrombin was determined using a thrombin-specific chromogenic assay. HA concentrations ranging from 250 to 1000 mug/ml significantly blocked the ability of antithrombin to inhibit thrombin in the presence of Ca2+ or Fe3+, and chondroitin A, B and C also reduced this ability under the same conditions but to a lesser extent. Our study suggests that the high concentration of free HA in RA synovium may block antithrombin locally, thereby deregulating thrombin activity to drive the pathogenic process of RA under physiological conditions. The study also helps to explain why RA occurs and develops in joint tissue, because the inflamed RA synovium is uniquely rich in free HA along with extracellular matrix degeneration. Our findings are consistent with those of others regarding increased coagulation activity in RA synovium.


T cell receptor biochemistry, repertoire selection and general features of TCR and Ig structure.
T cell recognition is a central event in the development of most immune responses, whether appropriate or inappropriate (i.e. autoimmune). We are interested in reducing T cell recognition to its most elemental components and relating this to biological outcome. In a model system involving a cytochrome c-specific I-Ek restricted T cell receptor (TCR) derived from the 2B4 hybridoma, we have studied the interaction of soluble TCR and soluble peptide-MHC complexes using surface plasmon resonance. We find a striking continuum in which biological activity correlates best with the dissociation rate of the TCR from the peptide-MHC complex. In particular, we have found that weak agonists have significantly faster off-rates than strong agonists and that antagonists have even faster off-rates. This suggests that the stability of TCR binding to a given ligand is critically important with respect to whether the T cell is stimulated, inhibited or remains indifferent. It also suggests that the phenomenon of peptide antagonists might be explained purely by kinetic models and that conformation, either inter- or intramolecular, may not be a factor. We have also studied TCR repertoire selection during the establishment of a cytochrome c response, initially using an anti-TCR antibody strategy, but more recently using peptide-MHC tetramers as antigen-specific staining reagents. These tetramers work well with either class I or class II MHC-specific TCRs and have many possible applications. Lastly, we have also tried to correlate the structural and genetic features of TCRs with their function. Recent data on TCR structure as well as previous findings with antibodies suggest that both molecules are highly dependent on CDR3 length and sequence variation to form specific contacts with antigens. This suggests a general "logic' behind TCR and Ig genetics as it relates to structure and function that helps to explain certain anomalous findings and makes a number of clear predictions.


Characterizing the cognitive effects of cocaine: a comprehensive review.
Understanding the cognitive sequela of repeated cocaine use is a growing area of research and is crucial to the development of cognitive models of addiction. We systematically reviewed all available placebo-controlled and case-controlled studies on the acute and long-term effects of cocaine on cognitive functioning. In order to compare the magnitude of cognitive effects across cognitive domains we conducted several meta-analyses on a subset of data from long-term effect studies. Studies on acute cocaine administration suggest enhancement of response inhibition and psychomotor speed, while all other domains appear to be unaffected or not investigated adequately. Long-term effects of cocaine show a wide array of deteriorated cognitive functions, indicating that long term cocaine use is characterized by a general cognitive impairment across functions, rather than by specific cognitive deficits. Literature on long-term cocaine effects is more substantial than literature on acute effects. This comprehensive review outlines possible dissociations and similarities of acute vs. long-term cocaine effects in the human brain. Atherosclerosis after cocaine exposure may underlie cognitive dysfunction, suggesting involvement of multiple brain areas. Acute drug studies are important to the future development of addiction models.


Distribution of molecular subtypes within Salmonella enterica serotype Enteritidis phage type 4 and S. Typhimurium definitive phage type 104 in nine European countries, 2000-2004: results of an international multi-centre study.
This study investigates the distribution of pulsed-field gel electrophoresis (PFGE) profiles within Salmonella enterica serotype Enteritidis phage type (PT) 4 and S. Typhimurium definitive phage type (DT) 104, from cases of human infection in nine European countries from 2000 to 2004. Isolates were subtyped using standardized methods and gel images submitted by each participating country to the coordinating centre (Health Protection Agency Centre for Infections, London, UK), where they were entered into a central database, developed within BioNumerics software, and designated using an agreed nomenclature. S. Enteritidis PT4 (n=3637) was differentiated into 38 different profiles. Simpson's index of diversity (D) of profiles ranged from 0.2 to 0.4. Profile SENTXB.0001 represented at least 80% of all profiles in each country. S. Typhimurium DT104 (n=1202) was differentiated into 28 different profile types. Simpson's D was at least 0.6 in all countries except in Austria and Italy. In both these countries over 74% of S. Typhimurium DT104 profiles were STYMXB.0013. Profile STYMXB.0061, was predominant in Denmark, Spain, Finland and England and Wales where it represented between 36% and 45% of profiles. Profile STYMXB.0001 represented nearly half of all profiles in Scotland and 23% in England and Wales. PFGE is proving useful for further discrimination within S. Enteritidis PT4 and S. Typhimurium DT104. Ascertainment of international outbreaks involving common serotypes and phage types may be increased by the timely pooling of PFGE profiles within a central database readily accessible to all participating countries.


A multigeneration reproductive and developmental safety evaluation of authentic Morinda citrifolia (noni) juice.
The impact of Morinda citrifolia (noni) juice on fertility and offspring health in three generations of ICR mice was evaluated. The authenticity of the source of noni juice in this study was determined by chemical analysis of known marker compounds. Mice were supplied with 5% noni juice at gestation (day 0) until weaning (21 days postpartum). This procedure was followed through three generations of offspring. Three generations of control mice were also evaluated. There were no intergroup differences in gestation and fertility indices or malformation rates. However, litter sizes of the noni group in the first (F1), second (F2), and third (F3) generations were, respectively, 29.3% (P < 0.01), 19.8% (P < 0.01) and 19.6% (P < 0.01) larger than corresponding controls. Despite larger litter sizes, there were no decreases in fetal weight in any generation of the noni group. Further, maternal health and offspring viability in the noni groups were equal to or greater than the controls. The results of this study suggest that authentic noni juice has no adverse effect on fertility and fetal development, consistent with previous two-generation studies of noni fruit from French Polynesia, Indonesia, and Hainan , China. On the contrary, noni juice appears to facilitate pregnancy and fetal development.


Epidemiological and clinical features, ultrasound findings and prognosis of right-sided infective endocarditis in a teaching hospital in Ouagadougou.
Right-sided infective endocarditis is rare. It accounts about 5 to 10% of all infective endocarditis cases and is prevalent in patients with congenital heart disease, intravascular devices and drug addiction. Our study aimed to describe the epidemiological, clinical and echocardiographic characteristics of right-sided endocarditis and evaluate the prognosis after treatment. From January 2010 to December 2011 we recruited all patients admitted to Yalgado Ouedraogo Teaching Hospital for infective endocarditis, and selected those who had a right-sided location. The Duke criteria were used for diagnosis. We analysed entry points and underlying heart disease. The causative organisms were tracked using blood sample cultures. Ultrasound characteristics were described, and treatment and prognosis were evaluated. Patients' follow up was conducted from recruitment to 30 June 2012. In the two-year period, 14 cases of right-sided infective endocarditis were recorded, including seven cases in children. They accounted for 29.1% of all infective endocarditis cases. The mean age was 25.5 ± 12.5 years (range 9-80 years). The venous route was implicated in 12 cases (85.7%). Blood cultures were positive in 11 patients. The bacteria isolated were Streptococcus pneumonia in six cases, Staphylococcus aureus in three and Hemophilus influenza in two cases. HIV status was positive in three patients. Underlying heart diseases were dominated by congenital heart disease in six cases and peripartal cardiomyopathy in four others. Vegetations were located in the right heart in only 11 cases. With antibiotic treatment, a lowering of temperature was shown within an average of 10 days of follow up. Two fatalities were reported. This study showed that right-sided endocarditis is common in our clinical practice. This infection was prevalent in patients with congenital heart disease or peripartal cardiomyopathy in our context, and the venous route seemed to be the main entry point.


Food matrix and processing modulate in vitro protein digestibility in soybeans.
Soybeans represent the largest source of plant proteins on the planet but their proteins are associated with low digestibility. Although several studies addressed the limiting factors affecting the rate and extent of soy protein digestion, the net effect of the food matrix, especially of an intact cell wall, has been poorly investigated so far. The purpose of the present study was to examine the relationship between the cell matrix and protein hydrolysis during simulated in vitro digestion of soybean particles of different sizes prepared from unheated and boiled cotyledons. In addition, intact cells were isolated from unheated and autoclaved cotyledons and then digested with and without lipase inhibitors to understand the impact of an intact cell wall and the presence of oil bodies on soybean protein digestibility. Protein digestibility was the highest in the particles prepared after boiling of previously milled cotyledons compared to particles of the same size obtained by milling previously cooked cotyledons as well as of uncooked cotyledons. Protein digestibility in isolated intact cells was lower than that of extracted proteins regardless of the thermal load applied whereas inhibition of pancreatic lipase reduces protein digestibility only slightly. The data indicated that the cell wall could contribute to limit protein digestion in soybean tissues; however, it is not an absolute barrier to pancreatic proteases. An accurate design of the milling and cooking process could be instrumental to modulate the digestion kinetics of soybean proteins.


Posterior Reversible Encephalopathy Syndrome (PRES) in 5-year-old girl with nephrotic syndrome.
Posterior Reversible Encephalopathy Syndrome (PRES) is a rare complication of nephrotic syndrome in children. This clinical condition is caused by localized brain angioedema mostly in parieto-occipital region and results in dramatic and acute features as sudden loss of consciousness, epileptic paroxysms, strong headache or visual disturbances. Uncontrolled hypertension often participates in PRES development. We present the case of a 5-year-old girl treated for relapse of nephrotic syndrome. At the time of edema regression and weight reduction, a sudden loss of consciousness and worsening of hypertension occurred. Brain MRI demonstrated extended multifocal changes strongly suspicious of encephalitis. After exclusion of herpetic encephalitis, the clinical picture was classified as PRES. Successful antihypertensive treatment led to general improvement of the girl's health within 48 hours and resolution of MRI brain hyperintensities occurred within the next three months. The aim of our case report is to us remind of possible development of PRES at the time of edema regression in nephrotic syndrome.


Efficacy and safety of same-day discharge after atrial fibrillation ablation compared with post-procedural overnight stay: a systematic review and meta-analysis.
Catheter ablation for atrial fibrillation (AF) has historically required inpatient admission post-procedure, but same-day discharge (SDD) has recently been reported. We aimed to assess the efficacy and safety of SDD compared with overnight stay (OS) post-ablation. We performed a systematic search of the PubMed database. Random-effects meta-analysis was performed to assess the efficacy (successful SDD) and safety (24 h complications, 30-day complications, 30-day re-admissions, and 30-day mortality) of a SDD AF ablation strategy. Fourteen non-randomized observational studies met criteria for inclusion, encompassing 26488 patients undergoing AF ablation, of whom 9766 were SDD. The mean age of participants was 61.9 years, and 67.9% were male. Around 61.7% underwent ablation for paroxysmal AF. The pooled success rate of SDD was 83.2% [95% confidence intervals (CIs): 61.5-97.0%, I2 100%]. The risk of bias was severe for all effect estimates due to confounding, as most cohorts were retrospectively identified without appropriately matched comparators. There was no significant difference in 30-day complications [odds ratio (OR): 0.95, 95% CI: 0.65-1.40, I2 53%] or 30-day re-admission (OR 0.96, 95% CI: 0.49-1.89, I2 82%) between groups. There were insufficient data for meta-analysis of 24 h complications and 30-day mortality. Where reported, no re-admissions occurred due to 24 h complications after SDD. Two deaths (0.04%) were reported in both SDD and OS groups. Same-day discharge after AF ablation appears to be an effective and safe strategy in selected patients. However, the available evidence is of low quality, and more robust prospective studies comparing SDD to OS are needed.


A statistical evaluation of the safety factor and species sensitivity distribution approaches to deriving environmental quality guidelines.
The species sensitivity distribution (SSD) distribution approach to estimating water quality guidelines (WQGs) is the preferred method in all jurisdictions reviewed (Australia, Canada, New Zealand, Organisation for Economic Co-operation and Development [OECD] members, South Africa, United States) and is one of the recommended methods for European Commission members for 33 priority and priority hazardous substances. In the event that jurisdiction-specific criteria for data quality, quantity, and taxonomic representation are not met, all of these jurisdictions endorse the use of additional safety factors (SFs) applied to either the SSD-based WQG or, the lowest suitable toxicity test endpoint. In Canada, the British Columbia Ministry of Environment endorses this latter approach as the preferred approach in the belief that so-derived WQGs are more protective than SSD-based WQGs. The level of protection afforded by the latter SF approach was evaluated by statistically sampling minima from random samples of the following distributions: normal, Gumbel, logistic, and Weibull, using a range of coefficients of variation (cVs) and applying the SFs of 2 or 10 used in British Columbia. The simulations indicate that the potentially affected fraction of species (PAF) can be as high as 20%, or, approach 0%. The PAF varies with sample size and CV. Because CVs can vary systematically with mode of toxic action, the PAF using SF-based WQGs can also vary systematically with analyte class. The varying levels of protection afforded by SF-based WQGs are generally inconsistent with the common water quality management goal that allows for a small degree of change under long-term exposure. The findings suggest that further efforts be made to develop high-quality WQGs that support informed decision making and are consistent with the environmental management goal instead of using SFs in the hope of achieving an acceptable but unknown, degree of environmental protection.


Effect of indomethacin and aspirin on the TNF-alpha-induced priming and protein tyrosyl phosphorylation of human neutrophils.
Receptor-mediated superoxide (O2-.)-generation in human peripheral neutrophils (HPPMN) is enhanced by various priming agents, such as granulocyte colony stimulating factor (G-CSF) and tumor necrosis factor (TNF-alpha). We previously reported that this enhancement occurred in parallel with the priming agent-induced increase in protein tyrosyl phosphorylation which is sensitive to tyrosine kinase (TK) inhibitors [Akimaru K. et al. Arch. Biochem. Biophys. 298:703, 1992]. We describe here that nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and aspirin, modulate the priming and tyrosine phosphorylation of HPPMN. The enhancement by TNF-alpha of formylmethionyl-leucyl-phenylalanine (FMLP)-induced O2-. generation was not inhibited by 5 microM azide, whereas that of FMLP-induced luminol chemiluminescence (LCL) was sensitive. Enhancement of FMLP-induced O2-. generation and LCL by priming agents was inhibited by both aspirin and indomethacin in a concentration dependent manner. This inhibition by the NSAIDs was much stronger than that for FMLP-induced O2-. generation without priming. The half-inhibition dose of indomethacin and aspirin were 50 microM and 1.5 mM, respectively. The priming-induced enhancement of tyrosyl phosphorylation of some neutrophil proteins, such as that of 108 and 115 kDa, was also inhibited by aspirin and indomethacin in a dose-dependent manner. However, dose dependent inhibition of the enhanced O2-. generation by the NSAIDs was not completely similar to that of enhanced tyrosyl phosphorylation. However, PKC-mediated O2-. generation, which has little sensitivity to TNF-alpha or G-CSF, was rather stimulated by the NSAIDs. These findings suggest that aspirin and indomethacin inhibit also the early steps of neutrophil activation as reflected by their ability to inhibit priming and the related tyrosyl phosphorylation of neutrophil proteins.


Medicare Accountable Care Organizations: Beneficiary Assignment Update.
This brief updates Brief No. 2014-3 and explains changes in the Centers for Medicare & Medicaid Services (CMS) Accountable Care Organization (ACO) regulations issued in June 2015 pertaining to beneficiary assignment for Medicare Shared Savings Program ACOs. Overall, the regulatory changes are intended to (1) encourage ACOs to participate in two-sided risk contracts, (2) increase the likelihood that beneficiaries are assigned to the physician (and ACO) from whom they receive most of their primary care services, and (3) make it easier for Federally Qualified Health Centers (FQHCs) and Rural Health Clinics (RHCs) to participate in ACOs. Understanding ACO beneficiary assignment policies is critical for ACO in managing their panel of ACO providers and beneficiaries.


Choroid plexus tumors in pediatric patients.
Choroid plexus tumors are rare intraventricular tumors, accounting for less than 1% of all intracranial tumors and 2-4% of brain tumors in children. The authors present their experience in the management of these lesions, and a review of the literature is performed. We retrospectively analyzed the outcome of pediatric patients with choroid plexus tumors treated with surgical resection. The patients' charts were reviewed for demographic data, clinical presentation, surgical therapy and follow-up. This study involves 18 consecutive choroid plexus tumors: 14 papillomas, 2 atypical papillomas and 2 carcinomas. The tumor was located in the lateral ventricles (12), the fourth ventricle (4) and the third ventricle (2). The mean age at presentation was 4.6 years. Surgical resection was performed in all cases and no patients died perioperatively. Survival rate of papilloma patients was 100% without evidence of recurrent disease (mean follow-up for 73 months). Survival rate of carcinoma patients was 50% (mean follow-up for 23.5 months). One carcinoma patient died of disseminated disease 13 months after surgery. The functional outcome in long-term survivors after papilloma surgery was excellent. Postoperative extraventricular drainage (EVD) was performed in 12 patients. Five patients (27.8%) had persistent hydrocephalus after tumor resection and required a ventriculoperitoneal shunt. Choroid plexus papilloma is a surgically curable disease. Postoperative EVD was considered effective in lowering the rate of shunt requirement through releasing the blood-tinged CSF and small particles of tumor residue.


Effects of hunger state on the brain responses to food cues across the life span.
The abundant exposure to food cues in our environment is one of the main drivers of overconsumption. Food evaluation is important for the regulation of food intake by the brain and it's interaction with hunger state. Children are especially susceptible to food cues. Understanding the mechanisms behind this regulation in healthy individuals across the life span can help to elucidate the mechanisms underlying overconsumption and aid the development of future obesity prevention strategies. Few functional neuroimaging studies have been done in children and elderly. Furthermore, it is unknown how hunger state affects neural food cue reactivity in these groups, since this has not been examined consistently. We examined the effects of hunger state and age on the brain responses to low- and high calorie foods. On two mornings, 122 participants (17 children; 38 teens; 36 adults; 31 elderly) performed a food image viewing task while being scanned using fMRI, either fasted or sated. Hunger induced greater activation during high versus low calorie food image viewing than satiety in the bilateral dorsomedial (dmPFC) and in the right dorsolateral prefrontal cortex (dlPFC) across all age groups. There was no significant main effect of age group on high versus low calorie food image viewing and no interaction between age group and hunger state. The greater activation of the dlPFC across all age groups during high calorie food image viewing in a fasted state might reflect increased inhibitory control in response to these foods. This may underlie the ability to resist overconsumption of high calorie foods. Furthermore, increased medial prefrontal cortex activation during hunger might reflect increased reward value of high calorie foods, which declines with satiation. Further studies are needed to better understand these results. Notably, overweight and obese individuals should be included to examine whether these responses are altered by weight status across the life span.


Seasonal variation of pollen collected by honey bees (Apis mellifera) in developed areas across four regions in the United States.
For honey bees (Apis mellifera), colony maintenance and growth are highly dependent on worker foragers obtaining sufficient resources from flowering plants year round. Despite the importance of floral diversity for proper bee nutrition, urban development has drastically altered resource availability and diversity for these important pollinators. Therefore, understanding the floral resources foraged by bees in urbanized areas is key to identifying and promoting plants that enhance colony health in those environments. In this study, we identified the pollen foraged by bees in four developed areas of the U.S., and explored whether there were spatial or temporal differences in the types of floral sources of pollen used by honey bees in these landscapes. To do this, pollen was collected every month for up to one year from colonies located in developed (urban and suburban) sites in California, Texas, Florida, and Michigan, except during months of pollen dearth or winter. Homogenized pollen samples were acetolyzed and identified microscopically to the lowest taxonomic level possible. Once identified, each pollen type was classified into a frequency category based on its overall relative abundance. Species richness and diversity indices were also calculated and compared across states and seasons. We identified up to 64 pollen types belonging to 39 plant families in one season (California). Species richness was highest in CA and lowest in TX, and was highest during spring in every state. In particular, "predominant" and "secondary" pollen types belonged to the families Arecaceae, Sapindaceae, Anacardiaceae, Apiaceae, Asteraceae, Brassicaceae, Fabaceae, Fagaceae, Lythraceae, Myrtaceae, Rhamnaceae, Rosaceae, Rutaceae, Saliaceae, and Ulmaceae. This study will help broaden our understanding of honey bee foraging ecology and nutrition in urban environments, and will help promote the use of plants that serve the dual purpose of providing aesthetic value and nutritious forage for honey bee colonies placed in developed landscapes.


Endovascular treatment of very small ruptured intracranial aneurysms: complications, occlusion rates and prediction of outcome.
To assess predictors of outcome following endovascular treatment of small ruptured intracranial aneurysms (SRA). Between 2004 and 2011, 91 patients with SRA (≤3 mm) were treated at our institution. Multivariate analysis was carried out to assess predictors of endovascular-related complications, aneurysm obliteration (>95%), recanalization and favorable outcome (Glasgow Outcome Scale 3-5). Endovascular treatment was aborted in nine of 91 patients (9.9%). Procedure-related complications occurred in eight of 82 patients (9.8%) of which five were transient and three were permanent. Three patients (3.7%) undergoing endovascular treatment experienced an intraprocedural aneurysm rupture. Three of nine patients (33.3%) treated with stent- or balloon-assisted coiling experienced periprocedural complications compared with five of 73 patients (6.8%) receiving only coils or Onyx (p=0.039). There were no procedural deaths or rehemorrhages. Rates of recanalization and retreatment were 18.2% and 12.7%, respectively. No factors predicted initial occlusion or recanalization. In multivariate analysis, pretreatment factors predictive of a favorable outcome included younger age (OR 0.94; 95% CI 0.91 to 0.99, p=0.017), larger aneurysm size (OR 3.4; 95% CI 1.02 to 11.11, p=0.045), Hunt and Hess grade (OR 0.38; 95% CI 0.19 to 0.75, p=0.005) and location (OR 5.12; 95% CI 1.29 to 20.25, p=0.02). When assessing treatment and post-treatment variables, vasospasm was the only additional covariate predictive of a poor outcome (OR 5.90; 95% CI 1.34 to 25.93,p=0.019). Most patients with SRA can be treated with endovascular therapy and have limited complications. Overall predictors of outcome for patients undergoing endovascular treatment of SRA include age, aneurysm size, Hunt and Hess grade, location and post-treatment vasospasm.


Role and evolution of viral tropism in patients with advanced HIV disease receiving intensified initial regimen in the ANRS 130 APOLLO trial.
The aims of the study were to assess in patients with advanced HIV disease receiving antiretroviral therapy (ART) intensification with enfuvirtide (i) resistance at virological failure (VF), (ii) impact of baseline tropism on immunovirological response, and (iii) HIV-1 DNA tropism evolution during ART. The ANRS 130 APOLLO randomized trial evaluated in naive patients the immunovirological impact of standard ART without (control arm) or with enfuvirtide. Tropism was determined on RNA and DNA by V3-loop sequencing interpreted using the Geno2Pheno algorithm. At baseline the median CD4 cell count was 30 cells/mm(3). Among the 170 patients assessable in this virological substudy, HIV-1 RNA tropism was as follows: 60% of viruses were R5 and 40% were R5X4/X4. HIV-1 DNA tropism was as follows: 54% were R5 and 46% were R5X4/X4. At week 24, 39% and 49% of patients experienced VF in the enfuvirtide and control arms, respectively. In the enfuvirtide arm, only resistance-associated mutations to enfuvirtide were detected. In the control arm, two patients displayed drug-resistant viruses at the time of VF. No impact of baseline tropism was observed on immunovirological response, regardless of the study arm. Among the 25 patients experiencing DNA tropism switch between baseline and week 24, 16 (64%) switched from R5 to R5X4/X4. These latter were mostly successfully suppressed patients receiving enfuvirtide and exhibiting poorer immunological response. Baseline RNA tropism had no impact on the immunovirological response. Drug resistance mutations were only detected for the fusion inhibitor. Finally, the mechanism of replenishment of the viral cellular reservoir with X4 viruses observed needs to be further analysed.


Dietary phytoestrogen, serum enterolactone and risk of prostate cancer: the cancer prostate Sweden study (Sweden).
Based on evidence that phytoestrogens may protect against prostate cancer, we evaluated the associations between serum enterolactone concentration or dietary phytoestrogen intake and risk of prostate cancer. In our Swedish population-based case-control study, questionnaire-data were available for 1,499 prostate cancer cases and 1,130 controls, with serum enterolactone levels in a sub-group of 209 cases and 214 controls. Unconditional logistic regression was performed to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with risk of prostate cancer. High intake of food items rich in phytoestrogens was associated with a decreased risk of prostate cancer. The OR comparing the highest to the lowest quartile of intake was 0.74 (95% CI: 0.57-0.95; p-value for trend: 0.01). In contrast, we found no association between dietary intake of total or individual lignans or isoflavonoids and risk of prostate cancer. Intermediate serum levels of enterolactone were associated with a decreased risk of prostate cancer. The ORs comparing increasing quartiles of serum enterolactone concentration to the lowest quartile were, respectively, 0.28 (95% CI: 0.15-0.55), 0.63 (95% CI: 0.35-1.14) and 0.74 (95% CI: 0.41-1.32). Our results support the hypothesis that certain foods high in phytoestrogens are associated with a lower risk of prostate cancer.


The mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) [but not D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP)] produces a nonopioid receptor-mediated increase in K+ conductance of rat locus ceruleus neurons.
The somatostatin analogues D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) have been used widely as selective antagonists of mu-opioid receptors. Actions of CTOP and CTAP on the membrane properties of rat locus ceruleus neurons were studied using intracellular recordings of membrane currents in superfused brain slices. CTOP increased a K+ conductance with an EC50 of 560 nM. The maximal conductance increase produced by CTOP (10 microM) was similar to that produced by high concentrations of the mu-opioid agonists D-Ala-Met-enkephalinglyol (1 microM) and Met-enkephalin (10 microM), as well as an alpha 2-adrenoceptor agonist (UK14304, 3 microM) and somatostatin (1 microM). The K+ current produced by CTOP was not antagonized by naloxone (1 microM), suggesting it was not mediated by mu-opioid receptors. The K+ currents induced by high concentrations of CTOP desensitized to 42% of the initial maximum after prolonged superfusion (t1/2 = 247 sec). In the presence of fully desensitized CTOP responses, somatostatin (1 microM) still produced near-maximal K+ currents; i.e., there was no cross-desensitization, which suggests that CTOP might act on a receptor distinct from somatostatin receptors. However, the converse did not apply; high concentrations of CTOP (30 microM) did not produce any additional current in the presence of desensitized somatostatin responses. No cross-desensitization was observed between CTOP (10-30 microM) and Met-enkephalin (30 microM) or nociceptin (3 microM) regardless of the order of drug application. Cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[Bzl], antagonized both somatostatin-(KD = 10 microM) and CTOP-(KD = 8 microM) induced K+ currents with similar potency. Concentrations of CTOP (100 nM) that produced a small K+ current partially antagonized the actions of Met-enkephalin (10 microM) on mu-opioid receptors. In contrast to CTOP, CTAP produced no K+ current at concentrations of 300 nM and 1 microM and little current at 10 microM. CTAP potently antagonized K+ currents produced by the mu-opioid receptor agonist D-Ala-Met-enkephalin-glyol, with an equilibrium dissociation constant of 4 nM (Schild analysis). CTAP did not antagonize K+ currents produced by CTOP or somatostatin. These results demonstrate that CTOP is a potent and efficacious agonist at nonopioid receptors, whereas CTAP is a potent mu-opioid receptor antagonist with little nonopioid agonist activity in rat locus ceruleus neurons. The receptor activated by CTOP has yet to be fully resolved but seems to be similar to the somatostatin type 2 receptor or perhaps to a receptor closely related to somatostatin or opioid receptors.


Evidence of a graphene-like Sn-sheet on a Au(111) substrate: electronic structure and transport properties from first principles calculations.
Two dimensional nanostructures of group IV elements have attracted a great deal of attention because of their fundamental and technological applications. A graphene-like single layer of tin atoms, commonly called stanene, has recently been predicted to behave like a quantum spin Hall insulator. Here we report the atomic structure, stability and electron transport properties of stanene stabilized on a gold substrate. The optimization of geometry and electronic structure was carried out using a plane-wave based pseudo-potential approach. This work is divided into three parts: (i) the nature of chemical interaction between tin atoms and the gold support, (ii) the geometrical shape and electronic structure of the tin layer on the gold support and (iii) the electron transport behavior of the gold supported tin layer. The results show that tin atoms bind to the gold support through strong chemical bonds and significant electronic charge transfer occurs from tin to the gold support. Remarkably, for a layer of tin atoms, while a buckled structure is preferred in the free state, a planar graphene-like atomic arrangement is stabilized on the gold support. This structural change corroborates the metal-like band structure of the planar stanene in comparison to the semi-metallic buckled configuration. The tunneling current of the supported tin layer shows Ohmic-like behavior and the calculated STM pattern of the supported tin layer shows distinct images of 'holes', characteristic of the hexagonal lattice.


The influence of Israel Health Insurance Law on the Negev Bedouin population--a survey study.
The extension of universal health service insurance to national populations is a relatively new phenomenon. Since 1995, the Israeli National Health Insurance Law (NHIL) has provided universal health services to every resident, but the effect of this law on health and health services among minorities has not been examined sufficiently. The goals of this study were to track some of the first changes engendered by the NHIL among the Negev Bedouin Arabs to examine the effects of universal health care services. Methods included analysis of historical and health policy documents, three field appraisals of health care services (1994, 1995, 1999), a region-wide interview survey of Negev Bedouins (1997), and key informant interviews. For the interview survey, a sample of 515 households was chosen from different Bedouin localities representing major sedentarization stages. Results showed that prior to the NHIL, a substantial proportion of the Negev Bedouins were uninsured with limited, locally available health service. Since 1995, health services, particularly primary care clinics and health manpower, have dramatically expanded. The initial expansion appears to have been a marketing ploy, but real improvements have occurred. There was a high level of health service utilization among the Bedouins in the Negev, especially private medical services, hospitals, and night ambulatory medical services. The NHIL brought change to the structure of health services in Israel, namely the institution of a national health system based on proportional allocation of resources (based on size and age) and open competition in the provision of quality health care. The expansion of the pool of potential members engendered by the new universal coverage had profound effects on the Health Funds' attitudes towards Negev Bedouins. In addition, real consumer choice was introduced for the first time. Although all the health care needs of this rapidly growing population have yet to be met fully, the assurances under the Law and the new level of competition promise a higher level of service in the future.


Serum Neurofilament Light Predicts Severity and Prognosis in Patients with Ischemic Stroke.
Serum neurofilaments are markers of axonal injury. We investigated whether serum neurofilament light (sNfL) is a potential prognostic marker of functional outcome in Chinese patients with acute ischemic stroke (AIS). From May 2015 to December 2018, consecutive patients with AIS from the Department of Neurology of the Second Hospital of Jilin University were included. sNfL concentration was tested at baseline, and stroke severity was analyzed at admission using the NIHSS score. Functional outcome was assessed at discharge by the modified Rankin scale (mRS). The sNfL concentration was tested in 343 patients with a median value of 17.8 (IQR, 13.4-25.2) pg/ml. sNfL concentration paralleled lesion size (P = 0.035). At admission, 174 patients were defined as moderate-to-high stroke (NIHSS ≥ 5); the sNfL concentration in those patients were higher than that observed in patients with minor clinical severity [21.2 (IQR, 15.1-31.7) vs. 14.9 (11.8-19.4) pg/ml, P < 0.001]. For each 1 quartile increase of sNfL concentration, the unadjusted and adjusted risk of moderate-to-high stroke increased by 202% (with the OR of 3.04 (95% CI 2.15-4.32), P < 0.001) and 102% [2.02 (1.10-3.16), P = 0.001), respectively. At discharge, 85 patients (24.8%) had poor functional outcome (mRS, 3-6); the sNfL concentration in those patients were higher than that observed in patients with good outcome [24.1 (IQR, 18.8-33.9) vs. 15.7 (11.9-21.8) pg/ml, P < 0.001]. For each 1 quartile increase of sNfL concentration, the unadjusted and adjusted risk of poor outcome increased by 236% [with the OR of 3.36 (95% CI 2.23-5.06), P < 0.001] and 102% [2.29 (1.37-3.82), P < 0.001], respectively. The results show sNfL is meaningful blood biomarker to monitor stroke severity and functional outcome in ischemic stroke, suggesting that sNfL may play a role in stroke progression.


SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome.
Prolonged SARS-CoV-2 RNA shedding and recurrence of PCR-positive tests have been widely reported in patients after recovery, yet these patients most commonly are non-infectious. Here we investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome and that transcription of the integrated sequences might account for PCR-positive tests. In support of this hypothesis, we found chimeric transcripts consisting of viral fused to cellular sequences in published data sets of SARS-CoV-2 infected cultured cells and primary cells of patients, consistent with the transcription of viral sequences integrated into the genome. To experimentally corroborate the possibility of viral retro-integration, we describe evidence that SARS-CoV-2 RNAs can be reverse transcribed in human cells by reverse transcriptase (RT) from LINE-1 elements or by HIV-1 RT, and that these DNA sequences can be integrated into the cell genome and subsequently be transcribed. Human endogenous LINE-1 expression was induced upon SARS-CoV-2 infection or by cytokine exposure in cultured cells, suggesting a molecular mechanism for SARS-CoV-2 retro-integration in patients. This novel feature of SARS-CoV-2 infection may explain why patients can continue to produce viral RNA after recovery and suggests a new aspect of RNA virus replication.


Individual, household and environmental risk factors for malaria infection in Amhara, Oromia and SNNP regions of Ethiopia.
We assessed malaria infection in relation to age, altitude, rainfall, socio-economic factors and coverage of control measures in a representative sample of 11437 people in Amhara, Oromia and SNNP regions of Ethiopia in December 2006-January 2007. Surveys were conducted in 224 randomly selected clusters of 25 households (overall sample of 27884 people in 5708 households). In 11538 blood slides examined from alternate households (83% of those eligible), malaria prevalence in people of all ages was 4.1% (95% CI 3.4-4.9), with 56.5% of infections being Plasmodium falciparum. At least one mosquito net or one long-lasting insecticidal net (LLIN) was present in 37.0% (95% CI 31.1-43.3) and 19.6% (95% CI 15.5-24.5) of households, respectively. In multivariate analysis (n=11437; 82% of those eligible), significant protective factors were: number of LLINs per household (odds ratio [OR] (per additional net)=0.60; 95% CI 0.40-0.89), living at higher altitude (OR (per 100 m)=0.95; 95% CI 0.90-1.00) and household wealth (OR (per unit increase in asset index)=0.79; 95% CI 0.66-0.94). Malaria prevalence was positively associated with peak monthly rainfall in the year before the survey (OR (per additional 10 mm rain)=1.10; 95% CI 1.03-1.18). People living above 2000 m and people of all ages are still at significant risk of malaria infection.


Disparities in human papillomavirus vaccine awareness among U.S. parents of preadolescents and adolescents.
Improved parental awareness of human papillomavirus (HPV) vaccines could increase uptake of vaccines early in the life course, thereby reducing adolescents' later risk for HPV infection and cancer. As such, we sought to determine factors related to parental awareness of HPV vaccines, using a nationally representative population-based sample. We examined data on 5735 parents of preadolescents and adolescents aged 8 to 17 years from the 2010 National Health Interview Survey. Parents were asked if they had ever heard of HPV vaccines or shots. Multivariable logistic regression analyses were used to examine the odds of parental awareness of HPV vaccines, controlling for relevant covariates. Most US parents (62.6%) heard of HPV vaccines. Multivariable results revealed parents of children who were older, female, and insured were more likely to have heard of HPV vaccines; parents who were female, white (non-Hispanic), English speakers, born in the United States, married or living with a partner, more educated, and had higher income were also more likely to be aware of HPV vaccines. Notably, parents of children who had a well-child checkup in the last 12 months were significantly more likely to have heard of HPV vaccines (odds ratio, 1.23; 95% confidence interval, 1.04-1.46). Given the significant disparities in parental awareness of HPV vaccines, improving access to preventive pediatric health care could offer an opportunity to increase parental awareness. In addition, public health efforts that provide culturally sensitive information in a variety of languages may be an effective way to reach vulnerable groups.


Predicting Teacher Participation in a Classroom-Based, Integrated Preventive Intervention for Preschoolers.
Preschools provide a promising setting in which to conduct preventive interventions for childhood problems, but classroom programs can only be effective if teachers are willing and able to implement them. This study is one of the first to investigate predictors of the frequency of teacher participation in a classroom-based, randomized controlled trial of an integrated prevention program for preschoolers. The intervention was designed to promote school readiness with an integrated social and academic program, to be implemented by teachers with the support of classroom consultants. The current study is part of a larger project conducted with Head Start and community child care centers that serve primarily economically disadvantaged families; 49 teachers from 30 centers participated in this study. Overall, teachers conducted approximately 70% of the program activities. Participation decreased significantly over time from the first to the final week of the intervention, and also decreased within each week of the intervention, from the first to the final weekly activity. Teachers working at community child care centers implemented more intervention activities than did Head Start teachers. Teacher concerns about the intervention, assessed prior to training, predicted less participation. In addition, teachers' participation was positively related to their perception that their centers and directors were supportive, collegial, efficient, and fair, as well as their job satisfaction and commitment. Teacher experience, education, ethnicity, and self-efficacy were not significantly related to participation. In multi-level models that considered center as a level of analysis, substantial variance was accounted for by centers, pointing to the importance of considering center-level predictors in future research.


Sensitivity and exposure to indoor allergens in adults with differing asthma severity.
In asthma, it is uncertain whether there is an association between degrees of exposure to domestic allergens and asthma severity. The pattern of sensitivity and exposure to common indoor allergens was examined in subjects with differing asthma severity. Sensitivity to house dust mite, dog and cat allergen and exposure to Der p 1, Can f 1 and Fel d 1 were assessed by skin prick tests and settled dust analysis in 28 subjects with severe asthma and 28 age- and sex-matched subjects with mild asthma (two declined skin prick test). All severe asthmatic subjects had at least one positive skin test and 20 of the 28 subjects were positive to all three allergens. Fourteen of the 26 subjects with mild asthma who took skin prick tests were positive to at least one, and one of these subjects was positive to the three allergens tested. Except for bedroom Fel d 1, the proportion of severe asthmatics both sensitized and exposed to each allergen at each site was significantly greater than the proportion sensitized and exposed in the mild asthma group. The geometric mean allergen concentrations, with the exception of bedroom Fel d 1, were greater in sensitized severe asthmatics than the sensitized mild asthmatics, which was significant for Der p 1 in bedroom samples and Can f 1 in bedroom and living room samples. These results support an association between the degrees of domestic allergen exposure in sensitized individuals and asthma severity.


Association of Childhood Blood Lead Levels With Criminal Offending.
Lead is a neurotoxin with well-documented effects on health. Research suggests that lead may be associated with criminal behavior. This association is difficult to disentangle from low socioeconomic status, a factor in both lead exposure and criminal offending. To test the hypothesis that a higher childhood blood lead level (BLL) is associated with greater risk of criminal conviction, recidivism (repeat conviction), conviction for violent offenses, and variety of self-reported criminal offending in a setting where BLL was not associated with low socioeconomic status. A total of 553 individuals participated in a prospective study based on a population-representative cohort born between April 1, 1972, and March 31, 1973, from New Zealand; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years (December 2012). Statistical analysis was performed from November 10, 2016, to September 5, 2017. Blood lead level measured at age 11 years. Official criminal conviction cumulative to age 38 years (data collected in 2013), single conviction or recidivism, conviction for nonviolent or violent crime, and self-reported variety of crime types at ages 15, 18, 21, 26, 32, and 38 years. Participants included 553 individuals (255 female and 298 male participants) who had their blood tested for lead at age 11 years. The mean (SD) BLL at age 11 years was 11.01 (4.62) μg/dL. A total of 154 participants (27.8%) had a criminal conviction, 86 (15.6%) had recidivated, and 53 (9.6%) had a violent offense conviction. Variety scores for self-reported offending ranged from 0 to 10 offense types at each assessment; higher numbers indicated greater crime involvement. Self-reported offending followed the well-established age-crime curve (ie, the mean [SD] variety of self-reported offending increased from 1.99 [2.82] at age 15 years to its peak of 4.24 [3.15] at age 18 years and 4.22 [3.02] at age 21 years and declined thereafter to 1.10 [1.59] at age 38 years). Blood lead level was a poor discriminator between no conviction and conviction (area under the curve, 0.58). Overall, associations between BLL and conviction outcomes were weak. The estimated effect of BLL was lower for recidivism than for single convictions and lower for violent offending than for nonviolent offending. Sex-adjusted associations between BLL reached statistical significance for only 1 of the 6 self-reported offending outcomes at age 15 years (r = 0.10; 95% CI, 0.01-0.18; P = .02). This study overcomes past limitations of studies of BLL and crime by studying the association in a place and time where the correlation was not confounded by childhood socioeconomic status. Findings failed to support a dose-response association between BLL and consequential criminal offending.


Metabolomic Profiling of Arginine Metabolome Links Altered Methylation to Chronic Kidney Disease Accelerated Atherosclerosis.
Atherosclerotic cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD), but the mechanisms underlying vascular disease has not been fully understood. As the nitrogen donor in nitric oxide (NO·) synthesis, arginine and its metabolic products are integrally linked to vascular health and information. We hypothesized that derangements in this pathway could explain, in part, increased atherosclerotic risk in CKD. We developed a targeted metabolomic platform to profile quantitatively arginine metabolites in plasma by liquid chromatography tandem mass spectrometry (LC/MS). Male low-density lipoprotein receptor defcient (LDLr-/-) mice at age 6 weeks were subjected to sham or 5/6 nephrectomy surgery to induce CKD. Subsequently, the animals were maintained on high fat diet for 24 weeks. Targeted metabolomic analysis of arginine metabolites in plasma was performed by isotope dilution LC/MS including asymmetric dimethyl arginine (ADMA), symmetric dimethyl arginine (SDMA), N-mono-methylarginine (NMMA), arginine and citrulline. Although elevated plasma levels of ADMA and SDMA were found in the CKD mice, only higher ADMA level correlated with degree of atherosclerosis. No significant differences were noted in levels of NMMA between the groups. CKD mice had high levels of citrulline and arginine, but ADMA levels had no correlation with either of these metabolites. These fndings strongly implicate altered arginine methylation and accumulation of ADMA, may in part contribute to CKD accelerated atherosclerosis. It raises the possibility that interrupting pathways that generate ADMA or enhance its metabolism may have therapeutic potential in mitigating atherosclerosis.


Five-week of solution-focused group counseling successfully reduces internet addiction among college students: A pilot study.
In the digital age, Internet addiction (IA) was deemed an epidemic and few treatments had been effectively developed for it. Here, we proposed a solution-focused group counseling (SFGC) as a potentially solution to reduce Internet addiction among college students. The present study examined the short- and long-term effect of a five-week solution-focused group counseling intervention on Internet addiction. Thirty-two participants were recruited and randomly assigned to either the experimental or control group, and twenty-six participants completed the whole intervention. The experimental group (n = 14) received the intervention, while control group (n = 12) did not. The revised version of the Chinese Internet Addiction Scale (CIAS-R), the Future Time Perspective, and resting-state EEG were administered pre-intervention, post-intervention, and at two follow-up tests (one month and six months after intervention). The results showed that the scores of the CIAS-R in the experimental group were significantly decreased after intervention, and these effects could be sustained for one month and six months follow-ups. Additionally, the intervention conducted an increase in future time perspective. EEG results further suggested that the alpha, beta, and gamma absolute power decreased after the intervention. These results from the pilot-study primarily suggested that solution-focused group counseling could be an effective intervention for Internet addiction.


Visualizing long-term memory formation in two neurons of the Drosophila brain.
Long-term memory (LTM) depends on the synthesis of new proteins. Using a temperature-sensitive ribosome-inactivating toxin to acutely inhibit protein synthesis, we screened individual neurons making new proteins after olfactory associative conditioning in Drosophila. Surprisingly, LTM was impaired after inhibiting protein synthesis in two dorsal-anterior-lateral (DAL) neurons but not in the mushroom body (MB), which is considered the adult learning and memory center. Using a photoconvertible fluorescent protein KAEDE to report de novo protein synthesis, we have directly visualized cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB)-dependent transcriptional activation of calcium/calmodulin-dependent protein kinase II and period genes in the DAL neurons after spaced but not massed training. Memory retention was impaired by blocking neural output in DAL during retrieval but not during acquisition or consolidation. These findings suggest an extra-MB memory circuit in Drosophila: LTM consolidation (MB to DAL), storage (DAL), and retrieval (DAL to MB).


Begging signals in a mobile feeding system: the evolution of different call types.
In some species, dependent offspring join foraging providers and beg for food. Mobile offspring might benefit from evolving begging signals adapted to the different situations they are exposed to, but this possibility has been ignored. In cooperatively breeding meerkats (Suricata suricatta), dependent offspring use a repertoire of several begging calls when joining foraging adults. We found that these calls can be differentiated on the basis of their acoustic structure and that pups adjusted the use of specific call types according to the social context. Pups continuously gave "repeat" calls when they accompanied foraging adults, and playback of these calls increased provisioning by the adults. When pups saw adults with food, they switched from repeat calls to vigorous "high-pitched" calls; adults also preferred to "feed" loudspeakers broadcasting high-pitched calls rather then loudspeakers broadcasting repeat calls. The elaboration of different begging calls might reflect an adaptation to a situation where dependent young must solicit food from potential feeders while at the same time directing feeders to bring the prey item to themselves and not to another begging pup. Here we show that mobile but dependent offspring adapt to different contexts in a mobile feeding system by using a repertoire of begging calls.


Prediction of the glass transition temperature and design of phase diagrams of butadiene rubber and styrene-butadiene rubber via molecular dynamics simulations.
To prevent car accidents, it is important to evaluate the thermal stability of tire rubbers, such as natural rubber (NR), butadiene rubber (BR), and styrene-butadiene rubber (SBR). Controlling the glass transition temperature (Tg) is the main factor for obtaining desirable thermal stability. Here, we developed an optimized equation for the prediction of the Tg of the various rubber systems using molecular dynamics (MD) simulations. We modeled a random copolymer system, blended monomers, and calculated the Tg of butadiene isomers in each composition. From these results, we designed the Tg contour of ternary cis-trans-vinyl butadiene and derived an equation of Tg for the ternary system. Moreover, we developed an equation to evaluate the pseudo-ternary Tg of quaternary SBR and plotted it. Our results present a novel way of predicting the Tg of ternary BR and quaternary SBR, which is critical for rational tire design with optimized thermal and mechanical stability.


Clinical outcome as a function of the PR-interval-there is virtue in moderation: data from the Duke Databank for cardiovascular disease.
Recently, a U-shaped association between PR-interval and the risk of developing atrial fibrillation was described, with higher risk in patients with long and short PR-intervals. Little is known regarding the association of PR-interval duration and mortality. The objective of the current study was to explore the relationship between PR-interval and major cardiovascular outcomes in patients with known coronary heart disease. Patients in sinus rhythm, undergoing coronary angiography at Duke University Medical Center between 1989 and 2010, who had significant stenosis in at least one native coronary artery, were included. Patients with arrhythmia, second- or third-degree AV-block, QRS > 120 ms were excluded. A total of 9,637 patients were included (median age 63, IQR 55-71 years, 67% men). After adjustment for relevant covariates, the risk of a CV event increased with a decreasing PR-interval (10 ms decrements) for PR-interval values <162 ms (all-cause mortality; HR 1.057, 95% CI 1.019-1.096, P = 0.0030, composite of death or stroke; HR 1.047, 95% CI 1.011-1.085, P = 0.0095 and composite of cardiovascular death or cardiovascular rehospitalization; HR 1.032, 95% CI 1.002-1.063, P = 0.0387). No statistically significant changes in the risk associated with PR-interval for values >162 ms were seen for any of the studied endpoints. In patients with coronary heart disease, a prolongation of the PR-interval was not independently associated with poor outcomes, but a PR-interval shorter than normal was associated with increased all-cause mortality and other major cardiovascular events.


Segments containing alternating purine and pyrimidine dinucleotides: patterns of polymorphism in humans and prevalence throughout phylogeny.
Tandem dinucleotide repeats of GT or AC [(GT)n/(AC)n] where n greater than or equal to 14 are highly polymorphic and other simple repeats such as (CT)n/(AG)n and (A)n(T)n are also polymorphic. The uniformity of these sequences precludes a mechanistic differentiation between recombination or polymerase slippage. Since (GT)n/(AC)n or (CT)n/(AG)n segments of desired size were not available in our gene of interest, we analyzed a 187+ bp segment in the factor IX gene with multiple short dinucleotide repeats. This sequence contains a melody of short dinucleotide repeats which includes a 142+ bp segment of alternating purines and pyrimidines. Amplification of this sequence in 167 individuals of different ethnicity and direct sequencing of 106 individuals (23 kb of sequence) failed to reveal simple variation in the number of tandem dinucleotide repeats. However, polymorphism in the 142+ alternating purine and pyrimidine segment (RY)n was detected due to the insertion of two related repeat units of 24 bp (A) and 26 bp (B). Two previously described alleles (AB, A2B2) and two novel presumptive recombinants were found (A2B, A3B2) for a total of four alleles. An analysis of (RY)n segments in GenBank revealed an extraordinary enrichment in the genome of mammals, invertebrates, and yeast and a marked reduction in bacteria. Rodent (RY)n were larger and substantially more frequent than those in primates. When a second (RY)n was examined in the exon 8 of human factor IX gene, it was polymorphic at short repeats of (GT)n/(AC)n (n = 3-6) in Western Europeans and Koreans. In addition, an (RY)n in the dystrophin gene had four polymorphic alleles involving AT and GT dinucleotides. Thus (RY)n segments appear to be abundant and highly polymorphic. The asymmetric patterns of polymorphism and the absence of simple dinucleotide variation in 23 kb of sequence are compatible with recombination or sister chromatid exchange, but not polymerase slippage. By inference, recombination should underlie the polymorphisms at (GT)n/(AC)n since they are a subset of (RY)n and they commonly occur in the context of longer (RY)n.


Structural basis for the inhibitory effect of brefeldin A on guanine nucleotide-exchange proteins for ADP-ribosylation factors.
Protein secretion through the endoplasmic reticulum and Golgi vesicular trafficking system is initiated by the binding of ADP-ribosylation factors (ARFs) to donor membranes, leading to recruitment of coatomer, bud formation, and eventual vesicle release. ARFs are approximately 20-kDa GTPases that are active with bound GTP and inactive with GDP bound. Conversion of ARF-GDP to ARF-GTP is regulated by guanine nucleotide-exchange proteins. All known ARF guanine nucleotide-exchange proteins contain a Sec7 domain of approximately 200 amino acids that includes the active site and fall into two classes that differ in molecular size and susceptibility to inhibition by the fungal metabolite brefeldin A (BFA). To determine the structural basis of BFA sensitivity, chimeric molecules were constructed by using sequences from the Sec7 domains of BFA-sensitive yeast Sec7 protein (ySec7d) and the insensitive human cytohesin-1 (C-1Sec7). Based on BFA inhibition of the activities of these molecules with recombinant yeast ARF2 as substrate, the Asp965-Met975 sequence in ySec7d was shown to be responsible for BFA sensitivity. A C-1Sec7 mutant in which Ser199, Asn204, and Pro209 were replaced with the corresponding ySec7d amino acids, Asp965, Gln970, and Met975, exhibited BFA sensitivity similar to that of recombinant ySec7d (rySec7d). Single replacement in C-1Sec7 of Ser199 or Pro209 resulted in partial inhibition by BFA, whereas replacement of Gln970 in ySec7d with Asn (as found in C-1Sec7) had no effect. As predicted, the double C-1Sec7 mutant with S199D and P209M was BFA-sensitive, demonstrating that Asp965 and Met975 in ySec7d are major molecular determinants of BFA sensitivity.


The immediate and long-term outcome of enhanced external counterpulsation in treatment of chronic stable refractory angina.
Treatment of angina recalcitrant to conventional pharmacological therapy and revascularization remains problematic. Safe, effective and affordable treatments with high patient acceptability are desirable. Enhanced external counterpulsation (EECP) may fulfil these criteria better than many other proposed interventions. To examine the immediate and long-term effect of EECP in treatment of chronic stable refractory angina. Prospective observational study of consecutive patients treated with EECP and follow-up for 1 year. Teaching hospital. Canadian Cardiovascular Society (CCS) angina grading, weekly angina frequency and glyceryl trinitrate (GTN) use. Sixty-one patients were treated with EECP and 58 completed a course of treatment. Further analysis is confined to those who completed EECP. About 52% of patients suffered from CCS III and IV angina prior to EECP. Immediately post-EECP, angina improved by at least one CCS class in 86% and by two classes in 59%. At 1-year follow-up, sustained improvement in CCS was observed in 78% of the patients. The median weekly angina frequency and GTN use were significantly reduced immediately after EECP [7 (4-14) vs. 1 (0-4) episodes per week and 7 (2-16) vs. 0 (0-2) times per week respectively, P < 0.0001; data in median (interquartile range)]. The reduction was sustained at 1-year follow-up. In 48 patients, their mean exercise time improved significantly after EECP [301 +/- 130 s vs. 379 +/- 147 s, P < 0.0001]. Major adverse treatment-related events were rare. This study shows that for patients who fail to respond to conventional measures, a high proportion gain symptomatic benefit from EECP.


Enhancement of fingermarks and visualizing DNA.
A novel method for detection and visualization of latent DNA using Diamond™ Nucleic Acid Dye (DD) staining has been developed. Applying DD to an object has the real potential to visualize DNA on a substrate from which a DNA profile can be generated, but it is important to determine whether this staining will adversely affect other forensic investigational techniques and vice versa. The aim of this study was to examine the interactions between staining a fingermark to detect DNA and then generate a DNA profile in combination with several standard latent fingermark enhancement methods. Six common fingerprint enhancements processes were chosen; (1) black powder, (2) black magnetic powder, (3) red magnetic powder, (4) white powder, (5) aluminum powder and (6) cyanoacrylate fuming. For all six methods, mark enhancement was carried out before DD staining and vice versa. DD is effective in detection of DNA in the presence of both aluminum and white finger mark powders and DD does not compromise the subsequent detection of ridge patterns if DD is applied first. Whilst magnetic powders could be used to successfully enhance latent fingermarks even after DD had been applied to them, latent DNA could not be observed in the marks irrespective of whether magnetic powder was applied before or after DD treatment. Magnetic powders did not adversely affect the profiling of DNA present in the marks. The application of DD to fingermarks did not adversely affect the enhancement of fingermarks using cyanoacrylate fuming. Whilst fluorescent particles resembling cells stained with DD were observed in marks either post-treated or pre-treated with cyanoacrylate vapor, DNA amplification and profiling was not successful. While it may be important in particular investigations to collect DNA profiles from latent fingermarks with continuous ridges and clear minutiae, the main utility of the technique described here would be in relation to investigations where enhancement has resulted in only partial or smudged marks. The results presented here indicate that if it is desirable to visualize latent DNA on an object but it is also planned to treat the object with cyanoacrylate vapor or magnetic powders then it is important to apply DD first, record the location of DNA and then apply the mark enhancement technique. For aluminum and white powder mark treatments such precautions are not important.


Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokers.
Sera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways. We performed immunoassays to detect autoantibodies to ten tumor associated antigens (TAAs) selected on the basis of previous studies showing that they had preferential specificity for certain cancers. Sera examined were from lung cancer patients (22); smokers with ground-glass opacities (GGOs) (46), benign solid nodules (55), or normal CTs (35); and normal non-smokers (36). Logistic regression models based on the antibody biomarker levels among the high risk and lung cancer groups were developed to identify the combinations of biomarkers that predict lung cancer in these cohorts. Statistically significant differences in the distributions of each of the biomarkers were identified among all five groups. Using Receiver Operating Characteristic (ROC) curves based on age, c-myc, Cyclin A, Cyclin B1, Cyclin D1, CDK2, and survivin, we obtained a sensitivity = 81% and specificity = 97% for the classification of cancer vs smokers(no nodules, solid nodules, or GGO) and correctly predicted 31/36 healthy controls as noncancer. A pattern of autoantibody reactivity to TAAs may distinguish patients with lung cancer versus smokers with normal CTs, stable solid nodules, ground glass opacities, or normal healthy never smokers.


Devastating decline of forest elephants in central Africa.
African forest elephants- taxonomically and functionally unique-are being poached at accelerating rates, but we lack range-wide information on the repercussions. Analysis of the largest survey dataset ever assembled for forest elephants (80 foot-surveys; covering 13,000 km; 91,600 person-days of fieldwork) revealed that population size declined by ca. 62% between 2002-2011, and the taxon lost 30% of its geographical range. The population is now less than 10% of its potential size, occupying less than 25% of its potential range. High human population density, hunting intensity, absence of law enforcement, poor governance, and proximity to expanding infrastructure are the strongest predictors of decline. To save the remaining African forest elephants, illegal poaching for ivory and encroachment into core elephant habitat must be stopped. In addition, the international demand for ivory, which fuels illegal trade, must be dramatically reduced.


Using the lower limit of normal for the FEV1/FVC ratio reduces the misclassification of airway obstruction.
The prevalence of airway obstruction varies widely with the definition used. To study differences in the prevalence of airway obstruction when applying four international guidelines to three population samples using four regression equations. We collected predicted values for forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) and its lower limit of normal (LLN) from the literature. FEV(1)/FVC from 40 646 adults (including 13 136 asymptomatic never smokers) aged 17-90+years were available from American, English and Dutch population based surveys. The prevalence of airway obstruction was determined by the LLN for FEV(1)/FVC, and by using the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society/European Respiratory Society (ATS/ERS) or British Thoracic Society (BTS) guidelines, initially in the healthy subgroup and then in the entire population. The LLN for FEV(1)/FVC varied between prediction equations (57 available for men and 55 for women), and demonstrated marked negative age dependency. Median age at which the LLN fell below 0.70 in healthy subjects was 42 and 48 years in men and women, respectively. When applying the reference equations (Health Survey for England 1995-1996, National Health and Nutrition Examination Survey (NHANES) III, European Community for Coal and Steel (ECCS)/ERS and a Dutch population study) to the selected population samples, the prevalence of airway obstruction in healthy never smokers aged over 60 years varied for each guideline: 17-45% of men and 7-26% of women for GOLD; 0-18% of men and 0-16% of women for ATS/ERS; and 0-9% of men and 0-11% of women for BTS. GOLD guidelines caused false positive rates of up to 60% when applied to entire populations. Airway obstruction should be defined by FEV(1)/FVC and FEV(1) being below the LLN using appropriate reference equations.


Prepuberal stimulation of 5-HT7-R by LP-211 in a rat model of hyper-activity and attention-deficit: permanent effects on attention, brain amino acids and synaptic markers in the fronto-striatal interface.
The cross-talk at the prefronto-striatal interface involves excitatory amino acids, different receptors, transducers and modulators. We investigated long-term effects of a prepuberal, subchronic 5-HT7-R agonist (LP-211) on adult behaviour, amino acids and synaptic markers in a model for Attention-Deficit/Hyperactivity Disorder (ADHD). Naples High Excitability rats (NHE) and their Random Bred controls (NRB) were daily treated with LP-211 in the 5th and 6th postnatal week. One month after treatment, these rats were tested for indices of activity, non selective (NSA), selective spatial attention (SSA) and emotionality. The quantity of L-Glutamate (L-Glu), L-Aspartate (L-Asp) and L-Leucine (L-Leu), dopamine transporter (DAT), NMDAR1 subunit and CAMKIIα, were assessed in prefrontal cortex (PFC), dorsal (DS) and ventral striatum (VS), for their role in synaptic transmission, neural plasticity and information processing. Prepuberal LP-211 (at lower dose) reduced horizontal activity and (at higher dose) increased SSA, only for NHE but not in NRB rats. Prepuberal LP-211 increased, in NHE rats, L-Glu in the PFC and L-Asp in the VS (at 0.250 mg/kg dose), whereas (at 0.125 mg/kg dose) it decreased L-Glu and L-Asp in the DS. The L-Glu was decreased, at 0.125 mg/kg, only in the VS of NRB rats. The DAT levels were decreased with the 0.125 mg/kg dose (in the PFC), and increased with the 0.250 mg/kg dose (in the VS), significantly for NHE rats. The basal NMDAR1 level was higher in the PFC of NHE than NRB rats; LP-211 treatment (at 0.125 mg/kg dose) decreased NMDAR1 in the VS of NRB rats. This study represents a starting point about the impact of developmental 5-HT7-R activation on neuro-physiology of attentive processes, executive functions and their neural substrates.