Occupational and environmental medicine in the United States: A proposal to abolish workers' compensation and reestablish the public health model.
The workers' compensation model of occupational and environmental medicine should be converted to a public health model. Occupational and environmental medicine, as a part of the public health infrastructure,could play a much more substantive part in bringing about a national program to deal with occupational and environmental health. The workers' compensation insurance system could be discontinued at any time,but it will be vital to do so when national health insurance is adopted in the United States. Abolishing workers' compensation would remove the perverse incentives that currently undermine the practice of occupational medicine. Medical care for workers should be provided by health care professionals who are not subject to influence by employers or insurers. Eligibility for benefits should not be determined by health and safety professionals. Wage-replacement benefits for workers should be determined by guidelines established by government and industry that prevent manipulation of health and safety professionals by employers and insurers. A nationwide comprehensive system to track work-related injury and illness, superior to the current reliance on records provided by employers and collated by government agencies, should be adopted. When unusually high rates of injuries, illnesses,and fatalities occur, government inspectors ought to respond and regulate the industry accordingly. Occupational health and safety professional strained in public health can and should participate in these activities, but not when they are in the employ of industry or insurers.


Pre-complexation of talin and vinculin without tension is required for efficient nascent adhesion maturation.
Talin and vinculin are mechanosensitive proteins that are recruited early to integrin-based nascent adhesions (NAs). In two epithelial cell systems with well-delineated NA formation, we find these molecules concurrently recruited to the subclass of NAs maturing to focal adhesions. After the initial recruitment under minimal load, vinculin accumulates in maturing NAs at a ~ fivefold higher rate than in non-maturing NAs, and is accompanied by a faster traction force increase. We identify the R8 domain in talin, which exposes a vinculin-binding-site (VBS) in the absence of load, as required for NA maturation. Disruption of R8 domain function reduces load-free vinculin binding to talin, and reduces the rate of additional vinculin recruitment. Taken together, these data show that the concurrent recruitment of talin and vinculin prior to mechanical engagement with integrins is essential for the traction-mediated unfolding of talin, exposure of additional VBSs, further recruitment of vinculin, and ultimately, NA maturation.


Climatic Fluctuations and the Diffusion of Agriculture.
This research examines the climatic origins of the diffusion of Neolithic agriculture across countries and archaeological sites. The theory suggests that a foraging society's history of climatic shocks shaped the timing of its adoption of farming. Specifically, as long as climatic disturbances did not lead to a collapse of the underlying resource base, the rate at which hunter-gatherers were climatically propelled to experiment with their habitats determined the accumulation of tacit knowledge complementary to farming. Consistent with the proposed hypothesis, the empirical investigation demonstrates that, conditional on biogeographic endowments, climatic volatility has a hump-shaped effect on the timing of the adoption of agriculture.


Interfacial ion solvation: Obtaining the thermodynamic limit from molecular simulations.
Inferring properties of macroscopic solutions from molecular simulations is complicated by the limited size of systems that can be feasibly examined with a computer. When long-ranged electrostatic interactions are involved, the resulting finite size effects can be substantial and may attenuate very slowly with increasing system size, as shown by previous work on dilute ions in bulk aqueous solution. Here we examine corrections for such effects, with an emphasis on solvation near interfaces. Our central assumption follows the perspective of Hünenberger and McCammon [J. Chem. Phys. 110, 1856 (1999)]: Long-wavelength solvent response underlying finite size effects should be well described by reduced models like dielectric continuum theory, whose size dependence can be calculated straightforwardly. Applied to an ion in a periodic slab of liquid coexisting with vapor, this approach yields a finite size correction for solvation free energies that differs in important ways from results previously derived for bulk solution. For a model polar solvent, we show that this new correction quantitatively accounts for the variation of solvation free energy with volume and aspect ratio of the simulation cell. Correcting periodic slab results for an aqueous system requires an additional accounting for the solvent's intrinsic charge asymmetry, which shifts electric potentials in a size-dependent manner. The accuracy of these finite size corrections establishes a simple method for a posteriori extrapolation to the thermodynamic limit and also underscores the realism of dielectric continuum theory down to the nanometer scale.


Biochemical changes in developmentally retarded Xenopus laevis larvae. I. The lens crystallin transition.
Premetamorphic tadpoles of Xenopus laevis reared in water containing 0.01% propylthiouracil are developmentally retarded and metamorphosis is prevented. When uncrowded, they continue to grow to a giant size. Moderate crowding leads to a slower rate of growth. Thus morphologically premetamorphic tadpoles were produced with lens diameters appropriate to either normal premetamorphic, climactic or post-metamorphic animals. The lens crystallins of such tadpoles have been separated by immunoelectrophoresis and polyacrylamide gel electrophoresis. The crystallin pattern was correlated with lens diameter rather than with body stage. Giant retarded larvae possessed crystallin patterns identical to those or normal adults. The thyroid antagonist propylthiouracil is therefore unable to prevent the lens crystallin transition, the beginning of which is normally temporally correlated with metamorphosis.


Fusarivirus accessory helicases present an evolutionary link for viruses infecting plants and fungi.
A significant number of mycoviruses have been identified that are related to plant viruses, but their evolutionary relationships are largely unexplored. A fusarivirus, Rhizoctonia solani fusarivirus 4 (RsFV4), was identified in phytopathogenic fungus Rhizoctonia solani (R. solani) strain XY74 co-infected by an alphaendornavirus. RsFV4 had a genome of 10,833 nt (excluding the poly-A tail), and consisted of four non-overlapping open reading frames (ORFs). ORF1 encodes an 825 aa protein containing a conserved helicase domain (Hel1). ORF3 encodes 1550 aa protein with two conserved domains, namely an RNA-dependent RNA polymerase (RdRp) and another helicase (Hel2). The ORF2 and ORF4 likely encode two hypothetical proteins (520 and 542 aa) with unknown functions. The phylogenetic analysis based on Hel2 and RdRp suggest that RsFV4 was positioned within the fusarivirus group, but formed an independent branch with three previously reported fusariviruses of R. solani. Notably, the Hel1 and its relatives were phylogenetically closer to helicases of potyviruses and hypoviruses than fusariviruses, suggesting fusarivirus Hel1 formed an evolutionary link between these three virus groups. This finding provides evidence of the occurrence of a horizontal gene transfer or recombination event between mycoviruses and plant viruses or between mycoviruses. Our findings are likely to enhance the understanding of virus evolution and diversity.


Dietary potassium and stroke-associated mortality. A 12-year prospective population study.
Hypertension is the most important known risk factor for stroke. Clinical, experimental, and epidemiologic evidence suggests that a high dietary intake of potassium is associated with lower blood pressure. In hypertensive rats, a high intake of potassium is reported to protect against stroke, even though blood pressure is not affected. We examined the relation between the 24-hour dietary potassium intake at base line and subsequent stroke-associated mortality in a population-based cohort of 859 men and women (aged 50 to 79 years) in Southern California. After 12 years, 24 stroke-associated deaths had occurred. The relative risks of stroke-associated mortality in the lowest tertile of potassium intake, as compared with that in the top two tertiles combined, were 2.6 (P = 0.16) in men and 4.8 (P = 0.01) in women. In multivariate analyses, a 10-mmol increase in daily potassium intake was associated with a 40 percent reduction in the risk of stroke-associated mortality (P less than 0.001). This effect was independent of other dietary variables, including the intake of calories, fat, protein, fiber, calcium, magnesium, and alcohol. The effect was also apparently independent of known cardiovascular risk factors, including age, sex, blood pressure, blood cholesterol level, obesity, fasting blood glucose level, and cigarette smoking. These findings support the hypothesis that a high intake of potassium from food sources may protect against stroke-associated death.


Application accuracy of the sleep decision tree to standardized patient cases by physiotherapists: An observational study.
Physiotherapists assess lifestyle factors, including sleep health, that contribute to poor health outcomes. Recommendations of sleep screening assessments have been provided; however, physical therapists' ability to successfully identify which patients would benefit from additional consultation has not been established. To determine if physiotherapists can accurately apply an evidence-based sleep decision tree to four hypothetical standardized patient cases. Participants applied the sleep decision tree to the four standardized cases via an online platform. Likert scales were used to assess perception of ease of use, likelihood of use, and how helpful they thought the sleep decision tree would be. Descriptive analyses and multiple linear regression models were conducted. Eighty-eight individuals participated in the study. Most participants correctly answered the cases with 1 and 3 decision points (92% and 84%, respectively). In contrast, few participants correctly answered the cases with 4 and 5 decision points (7% and 14%, respectively). Seventy-four (84%) respondents indicated the sleep decision tree was easy to use; 57 (65%) answered they were likely to use the sleep decision tree in clinical practice; and 66 (75%) said the sleep decision tree would be helpful to their clients. Physiotherapists were able to accurately apply a sleep decision tree to simpler patient cases but were frequently unable to apply it to more complex patient cases. This may be due to lack of education, perceived ease of using, and relevance of the sleep decision tree to their clinical practice. The sleep decision tree may aid physiotherapists in assessing sleep health, screening for sleep disturbances, and referring for further assessment.


A national overview of paediatric and adolescent and young adult surgical neuro-oncology in Pakistan.
To build a comprehensive brain tumour database that will allow us to analyse in detail the prevalence, demographics, and outcomes of the disease in paediatric, adolescent, and young adult age groups. A national cross-sectional study was conducted at 32 centres, and data regarding patient demographics and brain tumours were collected. This data was then stratified based on age groups, healthcare sectors, socioeconomic status, tumour types, and surgical outcomes. Most of the patients who were diagnosed with brain tumours belonged to a lower socioeconomic background and went to public sector hospitals. More males were diagnosed with and treated for brain tumours in the paediatric, adolescent, and young adult populations. The most common tumour in the paediatric population was medulloblastoma (23.7%) and the most common tumour in the adolescent (27.8%) and young adult population (34.7%) was glioma. Significant improvement in KPS scores were seen for: craniopharyngioma (p = 0.001), meningioma (p < 0.0005) and pituitary adenoma (p < 0.0005). This study shows that in all three age groups, there was a greater prevalence in males. Most of the patients belonged to a lower-middle-income class background and most patients presented to public sector hospitals. Greater knowledge of these parameters unique to each age group is the key to understanding and alleviating the burden of disease. Cancer registries, specifically brain tumour registries that keep up-to-date records of these patients, are essential to identify and keep track of these unique parameters to advance medical research and treatment strategies, ultimately lowering the disease burden.


Two new compounds, Talaromycin A and B, isolated from an endophytic fungus, Talaromyces aurantiacus.
Two new compounds Talaromycin A (1) and Talaromycin B (2) were isolated from a liquid culture of Talaromyces aurantiacus. The structures of 1 and 2 were elucidated by IR, MS, 1D and 2D NMR spectra and comparison of the experimental and calculated electronic circular dichroism spectra. Additional known compounds (3-6) were also isolated. These compounds were tested for monoamine oxidase, acetylcholinesterase and PI3K inhibitory activity, but showed only weak activity.


Effect of insulin on protein synthesis and degradation in skeletal muscle after exercise.
This study examined whether insulin stimulation of protein synthesis and inhibition of protein degradation is enhanced after exercise. The isolated perfused rat hindquarter preparation was used to evaluate net protein breakdown, myofibrillar protein degradation, and protein synthesis. Thirty minutes after treadmill exercise of high and moderate intensity, rates of tyrosine release were increased by 58 and 25%, respectively. Insulin at 75 microU/ml had no effect on these increases after intense exercise; however, 20,000 microU/ml of insulin totally inhibited this increase. Cycloheximide increased the tyrosine release in both control and exercised rat muscle. It also abolished the difference between them, suggesting that the increase in tyrosine release after exercise is caused by an inhibition of protein synthesis. Phenylalanine incorporation into protein was marginally depressed (22%, P = NS) in the white gastrocnemius muscle after intense exercise. Insulin at 200 microU/ml stimulated protein synthesis in these rats, but no more than it did in a nonexercised control group. Failure to observe a greater effect of insulin on protein metabolism was also noted when rat muscle was studied 150 min after intense exercise and after contractions induced by electrical stimulation of the sciatic nerve. These findings suggest that after exercise or electrically induced contractions the enhanced ability of insulin to stimulate hexose and amino acid transport is not paralleled by an increase in its ability to stimulate protein synthesis or inhibit protein degradation.


Luminescence and energy transfer mechanisms in photo-thermo-refractive glasses co-doped with silver molecular clusters and Eu3.
Silver molecular clusters were synthesized in photo-thermo-refractive glasses using the Na+-Ag+ ion exchange technique followed by heat treatment. Comprehensive study of cluster emission reveals the presence of spectrally separated fluorescence and phosphorescence with nanosecond and microsecond lifetime. Co-doping of glasses with Eu3+ was shown to results in quenching of cluster luminescence caused by energy transfer. The monitoring of silver cluster luminescence quantum yield and lifetime in the presence of Eu3+ indicates the presence of two different mechanisms of energy transfer. The first one affects the decay kinetics of cluster fluorescence and manifests at long distances, while the second one leads to static quenching of cluster emission at shorter distances and becomes prominent at higher doping Eu3+ concentration.


Use of ultrasound guidance for peripheral intravenous placement in difficult-to-access patients: advancing practice with evidence.
Placement of peripheral intravenous (PIV) lines in difficult-to-access patients can be daunting. Multiple unsuccessful peripheral sticks, numerous PIV restarts, and potentially excess use of peripherally inserted central catheters can result. The goals of this project were to decrease the number of peripherally inserted central catheter referrals and lower the number of PIV restarts by having clinical nurses employ ultrasound guidance when initiating deep PIVs. After 10 months of nurses using the ultrasound as needed to insert a PIV line, the number of total peripherally inserted central catheter referrals decreased by 20%.


Au nano-urchins enabled localized surface plasmon resonance sensing of beta amyloid fibrillation.
Early stage detection of neurodegenerative diseases such as Alzheimer's disease (AD) is of utmost importance, as it has become one of the leading causes of death of millions of people. The gradual intellectual decline in AD patients is an outcome of fibrillation of amyloid beta 1-42 (Aβ1-42) peptides in the brain. In this paper, we present localized surface plasmon resonance (LSPR) based sensing of Aβ1-42 fibrillation using Au nano-urchins. Strongly localized field confinement at the spiky nanostructures of nano-urchin surfaces enables them to detect very low concentrations of Aβ1-42. In addition, the LSPR peak of Au nano-urchins, which is very sensitive to ambient conditions, shows significant responses at different fibrillation stages of Aβ1-42. Reduction in LSPR peak intensity with an increase in the fibrillation is chosen as the sensing parameter here. This paper in this context provides LSPR based highly sensitive, label-free and real-time sensing of Aβ1-42 fibrillation that is highly advantageous compared to the existing techniques which require binding additives or fluorescent biomarkers.


Carbon metabolism and the sign of control coefficients in metabolic adaptations underlying K-ras transformation.
Metabolic adaptations are associated with changes in enzyme activities. These adaptations are characterized by patterns of positive and negative changes in metabolic fluxes and concentrations of intermediate metabolites. Knowledge of the mechanism and parameters governing enzyme kinetics is rarely available. However, the signs-increases or decreases-of many of these changes can be predicted using the signs of metabolic control coefficients. These signs require the only knowledge of the structure of the metabolic network and a limited qualitative knowledge of the regulatory dependences, which is widely available for carbon metabolism. Here, as a case study, we identified control coefficients with fixed signs in order to predict the pattern of changes in key enzyme activities which can explain the observed changes in fluxes and concentrations underlying the metabolic adaptations in oncogenic K-ras transformation in NIH-3T3 cells. The fixed signs of control coefficients indicate that metabolic changes following the oncogenic transformation-increased glycolysis and oxidative branch of the pentose-phosphate pathway, and decreased concentration in sugar-phosphates-could be associated with increases in activity for glucose-6-phosphate dehydrogenase, pyruvate kinase and lactate dehydrogenase, and decrease for transketolase. These predictions were validated experimentally by measuring specific activities. We conclude that predictions based on fixed signs of control coefficients are a very robust tool for the identification of changes in enzyme activities that can explain observed metabolic adaptations in carbon metabolism.


Electrostatic steering enhances the rate of cAMP binding to phosphodiesterase: Brownian dynamics modeling.
Signaling in cells often involves co-localization of the signaling molecules. Most experimental evidence has shown that intracellular compartmentalization restricts the range of action of the second messenger, 3'-5'-cyclic adenosine monophosphate (cAMP), which is degraded by phosphodiesterases (PDEs). The objective of this study is to understand the details of molecular encounter that may play a role in efficient operation of the cAMP signaling apparatus. The results from electrostatic potential calculations and Brownian dynamics simulations suggest that positive potential of the active site from PDE enhances capture of diffusing cAMP molecules. This electrostatic steering between cAMP and the active site of a PDE plays a major role in the enzyme-substrate encounter, an effect that may be of significance in sequestering cAMP released from a nearby binding site or in attracting more freely diffusing cAMP molecules.


Prelimbic prefrontal cortical encoding of reward predictive cues.
Animals appoint incentive value and learn to approach otherwise behaviorally inert stimuli if these stimuli come to predict the delivery of reward. Interestingly, this adaptive Pavlovian learning process has been implicated in behavioral control disorders, such as drug addiction. One brain region implicated in directing conditioned approach behavior is the prelimbic region of the prefrontal cortex. The present study employed in vivo electrophysiology in the prelimbic cortex to characterize the distribution of neural responses to the presence of a cue that had acquired incentive value after being associated with a primary reward. Male rats were trained in a Pavlovian autoshaping task in which a lever was presented prior to reward delivery. Following repeated pairings of lever availability and reward delivery, rats pressed the lever even though reward delivery was not contingent on any interaction with the lever. Neurons in the prelimbic cortex selectively encoded the presentation of the reward-predicting lever. Although the response was heterogeneous, most responsive neurons decreased their firing rate in response to the presence of the lever. These findings characterize the varied responses of prelimbic cortical neurons to reward cues and are consistent with evidence that the role of the prelimbic cortex in reward learning depends on the downstream target.


Enhancing E. coli isobutanol tolerance through engineering its global transcription factor cAMP receptor protein (CRP).
The limited isobutanol tolerance of Escherichia coli is a major drawback during fermentative isobutanol production. Different from classical strain engineering approaches, this work was initiated to improve E. coli isobutanol tolerance from its transcriptional level by engineering its global transcription factor cAMP receptor protein (CRP). Random mutagenesis libraries were generated by error-prone PCR of crp, and the libraries were subjected to isobutanol stress for selection. Variant IB2 (S179P, H199R) was isolated and exhibited much better growth (0.18 h(-1) ) than the control (0.05 h(-1) ) in 1.2% (v/v) isobutanol (9.6 g/L). Genome-wide DNA microarray analysis revealed that 58 and 308 genes in IB2 had differential expression (>2-fold, p < 0.05) in the absence and presence of 1% (v/v) isobutanol, respectively. When challenged with isobutanol, genes related to acid resistance (gadABCE, hdeABD), nitrate reduction (narUZYWV), flagella and fimbrial activity (lfhA, yehB, ycgR, fimCDF), and sulfate reduction and transportation (cysIJH, cysC, cysN) were the major functional groups that were up-regulated, whereas most of the down-regulated genes were enzyme (tnaA) and transporters (proVWX, manXYZ). As demonstrated by single-gene knockout experiments, gadX, nirB, rhaS, hdeB, and ybaS were found associated with strain isobutanol resistance. The intracellular reactive oxygen species (ROS) level in IB2 was only half of that of the control when facing stress, indicating that IB2 can withstand toxic isobutanol much better than the control.


Substrate specificity of the monooxygenase activity of hemoglobin.
Hemoglobin has been characterized as a monooxygenase-like catalyst of aniline hydroxylation both in reconstituted systems [ Mieyal et al. J. Biol. Chem. 251:3436-3441 (1976)] and in intact erythrocytes [ Blisard and Mieyal , J. Biol. Chem. 254:5104-5110 (1979)]. In this report, the monooxygenase activity of isolated hemoglobin (Hb) in the reconstituted system, which includes NADPH and cytochrome P-450 reductase, was shown to include N- and O-demethylation reactions besides p-hydroxylation, and to extend to other typical cytochrome P-450 substrates such as benzphetamine and p-nitroanisole. Some substrates were tested also with intact erythrocytes. Those which were metabolized displayed relative activities qualitatively similar to the pattern with isolated Hb. With isolated hemoglobin, complete kinetic analysis was carried out for 10 different reactions. The Km and Vmax values varied broadly, so that the efficiencies of the reactions (Vmax/Km) encompassed a range greater than 40,000. The most efficient reaction was O-demethylation of p-nitroanisole; the highest Vmax was observed for the O-demethylation of p-anisidine. The efficiencies (Vmax/Km) for a series of anisole derivatives (p-NH2,p-OH, p-H,p-NO2) was found to be quite sensitive to the electron-withdrawing effect of the p-substituent, i.e. a linear Hammett sigma rho relationship (log Vmax/Km versus sigma) was observed (p = 1.43). Metabolism of N-methylaniline by hemoglobin displayed distinct regioselectivity , with N-demethylation being favored over p-hydroxylation. Separate Km and Vmax values were observed for these two reactions of the single substrate, suggesting that distinct ternary O2-Hb-substrate complexes mediate the two reactions. In separate experiments, the various substrates were tested for their ability to accelerate autooxidation of HbO2 in the absence of NADPH and reductase. Aniline and its derivatives induced autooxidation with a concentration dependence matching their Km values for the corresponding hydroxylation reactions with the complete catalytic system. With the exception of p-hydroxyanisole, none of the other substrates accelerated autooxidation of HbO2. Hence this phenomenon cannot be an indicator of potential monooxygenase reactivity with hemoglobin. The broad and regioselective activities observed for hemoglobin resemble the characteristics of the authentic monooxygenase enzyme cytochrome P-450.


[Toxic action of nickel when taken up by the body from the drinking water].
Some aspects of the toxic effects of nickel were studied in a toxicological experiment for one year on male albino rats, administered perorally nickel in doses 0.0005, 0.005, 0.05 and 0.5 mg/kg, corresponding to 1/10 of the Soviet MAC respectively, MAC, 10 MAC and 100 MAC of nickel in potable waters, by the following indices: behaviour and general condition of the animals, body weight, weight coefficient of organs; total protein, blood sugar, glucose-6-phosphate dehydrogenase and lactate-dehydrogenase on serum; hemoglobin and erythrocytes in blood. The chronic nickel intoxication in doses of 0.5 mg/kg was established to lead to disorders in protein metabolism and reduction of body weight, in doses of 0.005, 0.05 and 0.5 mg/kg--to disorders in carbohydrate metabolism, erythrocytosis and hyperhemoglobinemia, and in doses of 0.0005 mg/kg--no changes have been established as regards all indices studied.


Defining the Genes Required for Survival of Mycobacterium bovis in the Bovine Host Offers Novel Insights into the Genetic Basis of Survival of Pathogenic Mycobacteria.
Tuberculosis has severe impacts on both humans and animals. Understanding the genetic basis of survival of both Mycobacterium tuberculosis, the human-adapted species, and Mycobacterium bovis, the animal-adapted species, is crucial to deciphering the biology of both pathogens. There are several studies that identify the genes required for survival of M. tuberculosis in vivo using mouse models; however, there are currently no studies probing the genetic basis of survival of M. bovis in vivo. In this study, we utilize transposon insertion sequencing in M. bovis AF2122/97 to determine the genes required for survival in cattle. We identify genes encoding established mycobacterial virulence functions such as the ESX-1 secretion system, phthiocerol dimycocerosate (PDIM) synthesis, mycobactin synthesis, and cholesterol catabolism that are required in vivo. We show that, as in M. tuberculosis H37Rv, phoPR is required by M. bovis AF2122/97 in vivo despite the known defect in signaling through this system. Comparison to studies performed in species that are able to use carbohydrates as an energy source, such as M. bovis BCG and M. tuberculosis, suggests that there are differences in the requirement for genes involved in cholesterol import (mce4 operon) and oxidation (hsd). We report a good correlation with existing mycobacterial virulence functions but also find several novel virulence factors, including genes involved in protein mannosylation, aspartate metabolism, and glycerol-phosphate metabolism. These findings further extend our knowledge of the genetic basis of survival in vivo in bacteria that cause tuberculosis and provide insight for the development of novel diagnostics and therapeutics. IMPORTANCE This is the first report of the genetic requirements of an animal-adapted member of the Mycobacterium tuberculosis complex (MTBC) in a natural host. M. bovis has devastating impacts on cattle, and bovine tuberculosis is a considerable economic, animal welfare, and public health concern. The data highlight the importance of mycobacterial cholesterol catabolism and identify several new virulence factors. Additionally, the work informs the development of novel differential diagnostics and therapeutics for TB in both human and animal populations.


[Planning in mental health--is it possible?].
The author opens the subject by questioning "why" and "how" to plan for mental health. Planification is a public health process. This process made modern countries able to develop health care policies in accordance to scientific progress. This allowed to stop the transmission of communicable diseases. Mental health disorders are one of the 4 public health priorities along with cardio-vascular diseases, cancers an consequences of accidents. New care methods have to be found in order to be adapted to recent needs. In many countries, mental health care have been and still are on the way to be modified. These major modifications will be illustrated by the French "sectorisation" which will be replaced in the context of complete reconversion of the French mental health care system. Two research streams will be proposed: research focused on the health care system which will enlight the different systems, their characteristics, activities and adequation; epidemiological studies in order to measure population needs in term of mental health, to clarify how mental health disorders appear and what sort of care are used by the persons. To illustrate these themas, the author will present his own experience. For more than 25 years he was operating on complex private mental health care system using the resources of an epidemiological unit in order to plan the development of this care system.


Biochemical and molecular characterization of a novel choline-specific glycerophosphodiester phosphodiesterase belonging to the nucleotide pyrophosphatase/phosphodiesterase family.
Nucleotide pyrophosphatases/phosphodiesterases (NPPs) are ubiquitous membrane-associated or secreted ectoenzymes that release nucleoside 5'-monophosphate from a variety of nucleotides and nucleotide derivatives. The mammalian NPP family comprises seven members, but only three of these (NPP1-3) have been studied in some detail. Previously we showed that lysophospholipase D, which hydrolyzes lysophosphatidylcholine (LPC) to produce lysophosphatidic acid, is identical to NPP2. More recently an uncharacterized novel NPP member (NPP7) was shown to have alkaline sphingomyelinase activity. These findings raised the possibility that other members of the NPP family act on phospholipids. Here we show that the sixth member of the NPP family, NPP6, is a choline-specific glycerophosphodiester phosphodiesterase. The sequence of NPP6 encodes a transmembrane protein containing an NPP domain with significant homology to NPP4, NPP5, and NPP7/alkaline sphingomyelinase. When expressed in HeLa cells, NPP6 was detected in both the cells and the cell culture medium as judged by Western blotting and by enzymatic activity. Recombinant NPP6 efficiently hydrolyzed the classical substrate for phospholipase C, p-nitrophenyl phosphorylcholine, but not the classical nucleotide phosphodiesterase substrate, p-nitrophenyl thymidine 5'-monophosphate. In addition, NPP6 hydrolyzed LPC to form monoacylglycerol and phosphorylcholine but not lysophosphatidic acid, showing it has a lysophospholipase C activity. NPP6 showed a preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids. It also hydrolyzed glycerophosphorylcholine and sphingosylphosphorylcholine efficiently. In mice, NPP6 mRNA was predominantly detected in kidney with a lesser expression in brain and heart, and in human it was detected in kidney and brain. The present results suggest that NPP6 has a specific role through the hydrolysis of polyunsaturated LPC, glycerophosphorylcholine, or sphingosylphosphorylcholine in these organs.


Effect of antihypertensive therapy on weight loss. The Trial of Antihypertensive Interventions and Management Research Group.
We report the effect of weight changes of the type of antihypertensive medication prescribed in a trial of the relative efficacy of drug and dietary measures in mild hypertension. The Trial of Antihypertensive Interventions and Management studied 878 mildly hypertensive individuals randomly assigned, in a 3 x 3 design, to no diet change, weight loss, or a low sodium-high potassium diet and to placebo, 25 mg chlorthalidone, or 50 mg atenolol. The type of drug prescribed affected weight change with all diets. The drug effect on weight change, present in all groups at 6 months, was most pronounced in those randomly assigned to the weight loss diet, where the placebo group lost 4.4 kg, the atenolol group lost 3.0 kg, and the chlorthalidone group lost 6.9 kg. The group differences were attenuated but persisted at 24 months. We suggest that the antihypertensive drug prescribed affects the success of a conjoint weight loss program and speculate that the difference between the drugs may be due to their intrinsic effects on the sympathetic nervous system and related metabolic changes.


Novel recombinant engineered gp41 N-terminal heptad repeat trimers and their potential as anti-HIV-1 therapeutics or microbicides.
Peptides derived from N-terminal heptad repeat (NHR) of the HIV-1 gp41 are generally poor inhibitors of HIV-1 entry, because they tend to aggregate and do not form a trimeric coiled-coil. In this study, we have fused portions of gp41 NHR, e.g. N36 or N28, to the T4 fibritin trimerization domain, Foldon (Fd), thus constructing novel NHR trimers, designated N36Fd or N28Fd, which could be expressed in Escherichia coli cells. The purified N36Fd and N28Fd exhibited SDS-resistant trimeric coiled-coil conformation with improved alpha-helicity compared with the corresponding N-peptides. They could interact with a C-peptide (e.g. C34) to form stable six-helix bundle and possessed potent anti-HIV-1 activity against a broad spectrum of HIV-1 strains. N28Fd was effective against T20-resistant HIV-1 variants and more resistant to proteinase K compared with T20 (enfuvirtide), a C-peptide-based HIV fusion inhibitor. Therefore, N28Fd trimer has great potentials for further development as an affordable therapeutic or microbicide for treatment and prevention of HIV-1 infection.


Visual Feedback Processing of the Limb Involves Two Distinct Phases.
Muscle responses to mechanical disturbances exhibit two distinct phases: a response starting at ~20 ms that is fairly stereotyped, and a response starting at ~60 ms modulated by many behavioral contexts including goal-redundancy and environmental obstacles. Muscle responses to disturbances of visual feedback of the hand arise within ~90 ms. However, little is known whether these muscle responses are sensitive to behavioral contexts. We had 49 human participants (27 male) execute goal-directed reaches with visual feedback of their hand presented as a cursor. On random trials, the cursor jumped laterally to the reach direction, and thus, required a correction to attain the goal. The first experiment demonstrated that the response amplitude starting at 90 ms scaled with jump magnitude, but only for jumps <2 cm. For larger jumps, the duration of the muscle response scaled with the jump size starting after 120 ms. The second experiment demonstrated that the early response was sensitive to goal redundancy as wider targets evoked a smaller corrective response. The third experiment demonstrated that the early response did not consider the presence of obstacles, as this response routinely drove participants directly to the goal even though this path was blocked by an obstacle. Instead, the appropriate muscle response to navigate around the obstacle started after 120 ms. Our findings highlight that visual feedback of the limb involves two distinct phases: a response starting at 90 ms with limited sensitivity to jump magnitude and sensitive to goal-redundancy, and a response starting at 120 ms with increased sensitivity to jump magnitude and environmental factors.SIGNIFICANCE STATEMENT The motor system can integrate proprioceptive feedback to guide an ongoing action in ~60 ms and is flexible to a broad range of behavioral contexts. In contrast, the present study identified that the motor response to a visual disturbance exhibits two distinct phases: an early response starting at 90 ms with limited scaling with disturbance size and sensitivity to goal-redundancy, and a slower response starting after 120 ms with increased sensitivity to disturbance size and sensitive to environmental obstacles. These data suggest visual feedback of the hand is processed through two distinct feedback processes.


Microplastic pollution in deep-sea sediments.
Microplastics are small plastic particles (<1 mm) originating from the degradation of larger plastic debris. These microplastics have been accumulating in the marine environment for decades and have been detected throughout the water column and in sublittoral and beach sediments worldwide. However, up to now, it has never been established whether microplastic presence in sediments is limited to accumulation hot spots such as the continental shelf, or whether they are also present in deep-sea sediments. Here we show, for the first time ever, that microplastics have indeed reached the most remote of marine environments: the deep sea. We found plastic particles sized in the micrometre range in deep-sea sediments collected at four locations representing different deep-sea habitats ranging in depth from 1100 to 5000 m. Our results demonstrate that microplastic pollution has spread throughout the world's seas and oceans, into the remote and largely unknown deep sea.


Predictive Parameters Identifying Men Eligible for a Sole MRI/Ultrasound Fusion-Guided Targeted Biopsy without an Additional Systematic Biopsy.
Evaluating the predictive factors that enable identifying men in which a sole MRI/ultrasound (MRI/US) fusion-guided targeted biopsy (TB) detects the maximal prostate cancer (PCa) risk group. Retrospective analysis of 251 consecutive patients who received a sensor-based, real-time MRI/US TB in combination with a 10-core systematic biopsy (SB) between August 2013 and July 2015. Univariate and multivariate binary regression analyses were performed to evaluate the predictors for equal/superior detection of the PCa risk group by TB compared to SB. TB detected PCa in 63% (157/251); SB detected PCa in 70% (176/251); a combination of TB and SB detected PCa in 77% (193/251) of cancer patients. Fifty percent (291/584) of TB cores and 22% (539/2,486) of SB cores showed PCa. Predictors for equal/superior performance of a sole TB were lesion size (maximal diameter; OR 1.050, 95% CI 1.002-1.101, p = 0.043), suspicious digital rectal examination (DRE; OR 2.448, 95% CI 1.062-5.645, p = 0.036) and free/total prostate-specific antigen (PSA) ratio (f/t PSA ratio) ≤0.15 (OR 0.916, 95% CI 0.867-0.967, p = 0.002) on univariate regression analysis and f/t PSA ratio ≤0.15 (OR 0.916, 95% CI 0.867-0.967, p = 0.002) on multivariate regression analysis. The maximal axial diameter of the Prostate Imaging Reporting and Data System-lesion and f/t PSA ratio and a suspicious DRE are possible selection criteria for men eligible for a sole MRI/US fusion-guided targeted prostate biopsy.


Towards a systematic method for assessing the impact of chemical pollution on ecosystem services of water systems.
Chemical pollution impinges on the quality of water systems and the ecosystem services (ESs) they provide. Expression of ESs in monetary units has become an essential tool for sustainable ecosystem management. However, the impact of chemical pollution on ESs is rarely quantified, and ES valuation often focuses on individual services without considering the total services provided by the ecosystem. The purpose of the study was to develop a stepwise approach to quantify the impact of sediment pollution on the total ES value provided by water systems. Thereby, we calculated the total ES value loss as a function of the multi-substance potentially affected fraction of species at the HC50 level (msPAF(HC50)). The function is a combination of relationships between, subsequently: the msPAF(HC50), diversity, productivity and total ES value. Regardless of the inherent differences between terrestrial and aquatic ecosystems, an increase of diversity generally corresponded to an increase in productivity with curvilinear or linear effects. A positive correlation between productivity and total values of ESs of biomes was observed. The combined relationships showed that 1% msPAF(HC50) corresponded to on average 0.5% (0.05-1.40%) of total ES value loss. The ES loss due to polluted sediments in the Waal-Meuse river estuary (the Netherlands) and Flemish waterways (Belgium) was estimated to be 0.3-5 and 0.6-10 thousand 2007$/ha/yr, respectively. Our study presents a novel methodology to assess the impact of chemical exposure on diversity, productivity, and total value that ecosystems provide. With sufficient monitoring data, our generic methodology can be applied for any chemical and region of interest and help water managers make informed decisions on cost-effective measures to remedy pollution. Acknowledging that the ES loss estimates as a function of PAF(HC50) are crude, we explicitly discuss the uncertainties in each step for further development and application of the methodology.


Effect of creatine on contents of myosin heavy chain and myosin-heavy-chain mRNA in steady-state chicken muscle-cell cultures.
Embryonic-chick muscle cells reach a steady state with respect to protein metabolism after approx. 1 week in cell culture. To determine if this steady state could be altered by the administration of agents that have been reported to stimulate myosin heavy-chain synthesis, 7-day muscle-cell cultures were treated with 0-1 mM-creatine. Incorporation of [3H]leucine into myosin heavy chain was stimulated by 30-40% at the optimum creatine concentration (0.2 mM), but this stimulation was blocked when actinomycin D (10 micrograms/ml) was also present. However, the quantity of myosin-heavy-chain mRNA as measured by hybridization in vitro was only 15% higher in creatine-treated cultures, and was therefore not entirely responsible for the observed effect. It is important to note that creatine only exerted its action on myosin-heavy-chain synthesis rate in steady-state cultures; creatine was ineffective in altering this rate in rapidly differentiating 3-day muscle cultures. Finally, muscle-cell cultures that had been grown for the entire 7-day culture period in the presence of 0.2 mM-creatine were assayed for quantity of myosin heavy chain. Control and creatine-treated cultures contained 12.7 +/- 1.5 and 20.5 +/- 1.8 micrograms/dish respectively. In conclusion, creatine apparently enhances the quantity of myosin heavy chain in steady-state embryonic muscle-cell cultures, but it probably does not mediate regulation of myosin content in adult skeletal muscle.


Regulation of mating type switching by the mating type genes and RME1 in Ogataea polymorpha.
Saccharomyces cerevisiae and its closely related yeasts undergo mating type switching by replacing DNA sequences at the active mating type locus (MAT) with one of two silent mating type cassettes. Recently, a novel mode of mating type switching was reported in methylotrophic yeast, including Ogataea polymorpha, which utilizes chromosomal recombination between inverted-repeat sequences flanking two MAT loci. The inversion is highly regulated and occurs only when two requirements are met: haploidy and nutritional starvation. However, links between this information and the mechanism associated with mating type switching are not understood. Here we investigated the roles of transcription factors involved in yeast sexual development, such as mating type genes and the conserved zinc finger protein Rme1. We found that co-presence of mating type a1 and α2 genes was sufficient to prevent mating type switching, suggesting that ploidy information resides solely in the mating type locus. Additionally, RME1 deletion resulted in a reduced rate of switching, and ectopic expression of O. polymorpha RME1 overrode the requirement for starvation to induce MAT inversion. These results suggested that mating type switching in O. polymorpha is likely regulated by two distinct transcriptional programs that are linked to the ploidy and transmission of the starvation signal.


Carbapenem-Nonsusceptible Gram-Negative Pathogens in ICU and Non-ICU Settings in US Hospitals in 2017: A Multicenter Study.
Infections caused by Gram-negative pathogens resistant to carbapenems have limited treatment options and are associated with increased morbidity and mortality. We evaluated the rates, infection sources, and pathogen types associated with carbapenem-nonsusceptible (Carb-NS) Gram-negative isolates in intensive care unit (ICU) and non-ICU settings in a large US hospital database. We conducted a retrospective cross-sectional analysis of carbapenem susceptibility of all nonduplicate isolates of Gram-negative pathogens collected from January 1, 2017, to December 31, 2017, at 358 US hospitals in the BD Insights Research Database. Carb-NS isolates included all pathogens reported at the institutional level as intermediate or resistant. Of 312 075 nonduplicate Gram-negative isolates, 10 698 (3.4%) were Carb-NS. Respiratory samples were the most frequent source of Carb-NS isolates (35.2%); skin/wound accounted for 23.6%. Pseudomonas aeruginosa was the most common Carb-NS pathogen (58.5% of isolates), and about 30% were Enterobacteriaceae. The highest rates of Carb-NS were found in Acinetobacter spp. (35.6%) and P. aeruginosa (14.6%). The rate of Carb-NS was significantly higher in ICU (5.4%) vs non-ICU settings (2.7%; P < .0001 in univariate analysis). This difference remained significant in multivariable analysis after adjusting for infection and hospital characteristics (odds ratio, 1.35; 95% confidence interval, 1.17-1.56; P < .0001). Infections caused by Carb-NS isolates pose a significant clinical problem across different sources of infection, species of pathogen, and hospital settings. Widespread infection prevention and antimicrobial stewardship initiatives, in combination with new treatment options, may be required to reduce the burden of carbapenem resistance in health care settings.


Tuning White Light Emission in Dinuclear Phenoxo Bridged DyIII Complexes.
A new series of dinuclear dysprosium(III) complexes, [Dy2(LCH3)2(NO3)2(MeOH)2] (I), [Dy2(LCH3)2(NO3)2(DMF)2]·2DMF (II), [Dy2(LCl)2(NO3)2(DMF)2]·2DMF (III), and [Dy2(LCH3O)2(NO3)2(DMF)2] (IV), with 2,2'-[[(2-pyridinylmethyl)imino]di(methylene)]bis(4-R-phenol), where R = CH3, Cl, and CH3O, were investigated as potential white light emitters. All octacoordinated dysprosium(III) are phenoxo-bridged species and have a similar coordination environment. Nevertheless, I has a MeOH ligand molecule, while for II-IV a DMF ligand replaces that of MeOH. The nature of the coordinated solvent molecule plays an important role in the behavior of the thermal dependence of the Y/B (yellow/blue) emission ratio of the DyIII complexes (Y: 4F9/2 → 6H13/2, yellow and B: 4F9/2 → 6H15/2, blue transitions),, since for I the variation of this ratio is significant, while for the other DyIII complexes with DMF as ligand the ratio remains constant within experimental error. At room temperature the CIE (Commission International d'Eclairage) color coordinates for the DyIII complexes, I (0.286, 0.317), III (0.302, 0.324), and IV (0.322, 0.348) are close to the NTSC (National Television System(s) Committee) standard value for white color. Varying the temperature from 16 to 300 K the CIE coordinates for I change from the blueish to white region of the chromaticity diagram, while those of II present an inverse thermal dependence as compared to I. The CCT (Correlated Color Temperature) values at room temperature for I (8384 K), II (17235 K), and IV (5948 K) permit us to consider these complexes as candidates for white cold light emitters, the high value of II being uncommon. For I and II the CCT values vary strongly with temperature, showing a decrease with increasing temperature for I, and an increase with increasing temperature for II, thus making evident the influence on the photophysical properties of the nature of the coordinated solvent molecule in these complexes.


Interproximal tissue maintenance in GTR procedures: description of a surgical technique and 1-year reentry results.
Guided tissue regeneration procedures often result in the loss of gingival tissue. This postoperative problem is associated with the treatment of interproximal periodontal defects. A surgical technique is presented which preserves the interproximal tissue, facilitating primary and sustained coverage of the guided tissue regeneration barrier. Twelve interproximal defects were treated with this technique using Gore-Tex Periodontal Material. The Gore-Tex Periodontal Material remained in place for 4 months. The sites were reentered at 1 year and clinical parameters were recorded. At 4 months, 11 of 12 sites demonstrated no exposure of the Gore-Tex Periodontal Material. Mean gain in bone fill was 95%, and three sites demonstrated supracrestal bone deposition. Only 0.58 mm of gingival recession occurred. This study suggests that with ideal gingival flap management, enhanced regenerative and esthetic results can be achieved.


Treatment Satisfaction and Its Associated Factors of Dolutegravir Based Regimen in a Resource Limited Setting.
Treatment satisfaction is patient's evaluation of the process of taking the medication and its use. Currently dolutegravir based regimen is first-line agent for treatment of human immunodeficiency virus. But evidence is scarce regarding treatment satisfaction. Thus, the aim of the current study was to assess treatment satisfaction and associated factors of dolutegravir based regimen among adult human immunodeficiency virus patients attending at Debre Markos referral 2020. Institutional-based cross-sectional study was conducted. A systematic random sampling technique was used to collect data from June 25 to August 25, 2020 at Debre Markos referral hospital. It was entered into Epi Info and exported to SPSS version 23 for analysis. Bivariable and multivariable logistic regression was used to identify factors. Variables with p<0.05 were considered as statistically significant. From a total of 359, 349 participants (97.2%) responded to the study. In this study, 70.5% of participants reported higher treatment satisfaction. Monthly average income of ≥3500 birr (AOR: 2.88; 95% CI: 1.26, 6.58), 1600-2500 birr (AOR: 2.47; 95% CI: 1.11, 5.48), 800-1600 birr (AOR: 3.11; 95% CI: 1.31, 7.37), positive belief about medications (AOR: 3.05; 1.76, 5.28), having a discussion with health care providers (AOR: 3.05, 95% CI: 1.58, 5.88), patients without concurrent medication (AOR: 7.72, 95% CI: 3.29, 18.07), and being male (AOR: 2.10, 95% CI: 1.14, 3.87) were associated with treatment satisfaction. Overall, dolutegravir based regimen showed high treatment satisfaction. Monthly income, positive beliefs about medications, discussing about treatment options, sex and concurrent medications were associated with treatment satisfaction. Thus, it is crucial to improve treatment satisfaction by promoting positive belief towards medication and also by engaging patients in treatment decisions.


The protein Slr1143 is an active diguanylate cyclase in Synechocystis sp. PCC 6803 and interacts with the photoreceptor Cph2.
Cyclic-di-GMP is an ubiquitous second messenger in bacteria. Several c-di-GMP receptor proteins have been identified to date, and downstream signalling pathways are often mediated through protein-protein interactions. The photoreceptor Cph2 from the cyanobacterium Synechocystis sp. PCC 6803 comprises three domains related to c-di-GMP metabolism: two GGDEF and one EAL domain. It has been shown that the C-terminal GGDEF domain acts as blue-light triggered c-di-GMP producer thereby inhibiting motility of the cells in blue light. The specific function of the other two c-di-GMP related domains remained unclear. In this study, we test knockout mutants of potential interaction partners of Cph2 for altered phototactic behaviour. Whereas wild-type cells are non-motile under high-intensity red light of 640 nm, the mutant Δslr1143 displays positive phototaxis. This phenotype can be complemented by overexpression of full-length Slr1143, which also results in an increased cellular c-di-GMP concentration. However, the non-motile phenotype of wild-type cells under high-intensity red light appears not to be due to an elevated cellular c-di-GMP content. Using co-precipitation and yeast two-hybrid assays, we demonstrate that the GGDEF domain of Slr1143 interacts with the EAL and the GGDEF domains of Cph2. However, under the test conditions, the interaction of the two proteins is not light-dependent. We conclude that Slr1143 is a new Cph2-interacting regulatory factor which modulates motility under red light and accordingly we propose Cip1 (Cph2-interacting protein 1) as a new designation for this gene product.


Snake spectacle vessel permeability to sodium fluorescein.
Assess vascular permeability of the snake spectacle to sodium fluorescein during resting and shedding phases of the ecdysis cycle. Ball python (Python regius). The snake was anesthetized, and spectral domain optic coherence tomography was performed prior to angiographic procedures. An electronically controlled digital single-lens reflex camera with a dual-head flash equipped with filters suitable for fluorescein angiography was used to make images. Sodium fluorescein (10%) solution was administered by intracardiac injection. Angiographic images were made as fluorescein traversed the vasculature of the iris and spectacle. Individually acquired photographic frames were assessed and sequenced into pseudovideo image streams for further evaluation CONCLUSIONS: Fluorescein angiograms of the snake spectacle were readily obtained. Vascular permeability varied with the phase of ecdysis. Copious leakage of fluorescein occurred during the shedding phase. This angiographic method may provide diverse opportunities to investigate vascular aspects of snake spectacle ecdysis, dysecdysis, and the integument in general.


Natural products target glycolysis in liver disease.
Mitochondrial dysfunction plays an important role in the occurrence and development of different liver diseases. Oxidative phosphorylation (OXPHOS) dysfunction and production of reactive oxygen species are closely related to mitochondrial dysfunction, forcing glycolysis to become the main source of energy metabolism of liver cells. Moreover, glycolysis is also enhanced to varying degrees in different liver diseases, especially in liver cancer. Therefore, targeting the glycolytic signaling pathway provides a new strategy for the treatment of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis associated with liver cancer. Natural products regulate many steps of glycolysis, and targeting glycolysis with natural products is a promising cancer treatment. In this review, we have mainly illustrated the relationship between glycolysis and liver disease, natural products can work by targeting key enzymes in glycolysis and their associated proteins, so understanding how natural products regulate glycolysis can help clarify the therapeutic mechanisms these drugs use to inhibit liver disease.


Bacteria Associated with the Gut Tract of Larval Stages of the Aquatic Cranefly Tipula abdominalis (Diptera; Tipulidae).
Scanning electron microscopy, light microscopy, and direct isolations were used to examine the distribution and diversity of bacteria in the gut tracts of larval stages of Tipula abdominalis. The animal had an enlarged hindgut which housed a diverse bacterial community in the lumen and directly attached to the gut wall. Distinct localization was noted, with the most dense and most diverse community anterior to the rectum. A distinct architecture of bacteria occurred in this region, characterized by a layering or a "weblike" array of filamentous bacteria overlying mats of bacteria closely associated with the gut wall. Although morphological diversity was high in the hindgut, filamentous bacteria were the dominant morphology observed. The attached microbiota, sloughed during ecdysis, recolonized to the same density and diversity observed before the molt. The majority of the isolatable bacterial types were facultatively anaerobic. The distinct localization and attached nature of the hindgut bacteria and the recolonization after each molt suggest they are indigenous to this region of the gut tract.


Evidence for the involvement of orbitofrontal cortex in memory functions: an interference effect.
Although it is frequently stated that the frontal lobes play a significant role in memory function, research proof has been ambiguous at best. This problem was addressed by administering a variety of memory tests to 16 schizophrenic patients who had undergone prefrontal leucotomy approximately 25 years earlier. The 16 were divided into three groups on the basis of recovery after surgery. Two comparison groups were established to control for psychiatric symptomatology, years of institutionalization, age, and years of education. The results demonstrate that large bilateral orbitofrontal lesions may not result in amnesia; in fact, the nonoperated schizophrenic control group performed the most poorly. Proactive interference was demonstrated, however, resulting in significant impairment for all patients with prefrontal lobe damage despite normal scores on commonly used memory tests. Ability to maintain consistent and directed attention and to overcome interference is proposed as a role of the frontal lobes in memory function.


Long-term prognosis of patients with cardiac syndrome X.
Previous follow-up studies of patients with cardiac syndrome X (CSX) reported good prognosis. However, some recent reports challenged this finding by showing appreciable mortality rates in patients with angina and normal coronary arteries admitted for acute coronary syndromes. We performed clinical follow-up of 155 patients (mean age 58.9+/-10 years, 40 men) with typical CSX. The occurrence of major cardiac events (cardiac death, acute myocardial infarction), readmission for chest pain, revascularization procedures, angina status, and non cardiac events during follow-up were collected for each patient. At a mean follow-up time of 137+/-78 months (range 24-372) from the onset of symptoms, 4 patients died, 3 for cancers and 1 for acute pancreatitis. No patient died from cardiovascular causes or had any major cardiovascular event. Hospital readmission for recurrent chest pain was reported by 89 patients (58%), and 33 (22%) underwent at least one more coronary angiography. During follow-up, chest pain had remained unchanged in 33% of patients and had worsened in 14% of patients. Our data show that patients with CSX have excellent long-term clinical prognosis. A significant number of patients, however, shows persistence or worsening of symptoms, as well as further recurrence to medical evaluation.


[RET rearrangements in advanced lung cancer: a target to always look for.]
Introduction . RET rearrangements have been recently aroused growing interest, due to the availability of target therapies increasingly active and safe. The search for these oncogenic alterations in patients with advanced lung adenocarcinoma has become an integral part of the biomolecular tumoral assessment, in order to possibly provide a selective therapeutical option also for rare subgroups of patients, but belonging to lung cancer that is considered a "big killer", representing the most frequent cause of cancer-related death worldwide. Following to the introduction of modern biomolecular techniques, such as the comprehensive genome profiling (CGP), that has been added to the immunohistochemistry (IHC) and the "in situ fluorescent ibridation" (FISH), the availability of techniques based on genomic sequencing such as the next generation sequencing (NGS), achievable either on tumoral tissue or on plasma, has made it easier to identify oncogenic alterations that, although rare, are potentially treatable with molecularly targeted drugs. A complete molecular assessment should preferable be obtained at the first diagnosis, in order not to neglect the possibility of using target drugs if indicated, but it is possible and desiderable to complete or to re-determine the biomolecular profile also during the clinical course, due to the possibility of spontaneous or drug-induced resistance mechanisms that can modify the biomolecular tumoral characteristics; this reassessment is achievable both through tissutal rebiopsy and by plasma test, the so-called "liquid biopsy". Clinical case . In this report, we describe the case of a patient with advanced lung adenocarcinoma, pretreated with multiple chemo- and immuno-therapic lines of treatment; at baseline, the biomolecular profile was not complete, as well as during the clinical course through repeated re-biopsies. Conclusions . At the time of further disease progression, a liquid biopsy with NGS revealed the presence of a RET rearrangement. This clinical case underscores the importance of a complete biomolecolar assessment in order to identify target linked to effective and innovative treatment options; it is also highlighted the usefulness of the modern CGP techniques, applicable to tumoral tissue and plasma.


Vagus Nerve Stimulation Alters Phase Synchrony of the Anterior Cingulate Cortex and Facilitates Decision Making in Rats.
Vagus nerve stimulation (VNS) can enhance memory and cognitive functions in both rats and humans. Studies have shown that VNS influenced decision-making in epileptic patients. However, the sites of action involved in the cognitive-enhancement are poorly understood. By employing a conscious rat model equipped with vagus nerve cuff electrode, we assess the role of chronic VNS on decision-making in rat gambling task (RGT). Simultaneous multichannel-recordings offer an ideal setup to test the hypothesis that VNS may induce alterations of in both spike-field-coherence and synchronization of theta oscillations across brain areas in the anterior cingulate cortex (ACC) and basolateral amygdala (BLA). Daily VNS, administered immediately following training sessions of RGT, caused an increase in 'good decision-maker' rats. Neural spikes in the ACC became synchronized with the ongoing theta oscillations of local field potential (LFP) in BLA following VNS. Moreover, cross-correlation analysis revealed synchronization between the ACC and BLA. Our results provide specific evidence that VNS facilitates decision-making and unveils several important roles for VNS in regulating LFP and spike phases, as well as enhancing spike-phase coherence between key brain areas involved in cognitive performance. These data may serve to provide fundamental notions regarding neurophysiological biomarkers for therapeutic VNS in cognitive impairment.


Evaluation of the Use of Diverse Mental Health Simulation in Nursing Students' Learning Experience: An International Multisite Study.
Simulated patients (SPs) in mental health nursing education provide a unique approach to assist student development in complex assessment skills. The purpose of this international multisite study was to evaluate the use of two diverse mental health SP simulation scenarios on nursing students' satisfaction and self-confidence in learning to care for patients with mental health disorders in the United States (n = 70) and Turkey (n = 90). A multisite cross-sectional study design was used. Outcome measures included the Student Satisfaction and Self-confidence in Learning Scale and the adapted Simulation Effectiveness Tool-Modified. Results were analyzed using independent t tests. While students in the United States reported higher perceived self-confidence and satisfaction in learning, both student populations found the intervention effective to their learning (P < .05). Using SPs in mental health education allow students to practice their assessment skills learned in classroom and transfer them to the clinical area.


Sweetened Beverage Consumption and Risk of Biliary Tract and Gallbladder Cancer in a Prospective Study.
Sugar-sweetened beverage consumption raises blood glucose concentration and has been positively associated with weight gain and type 2 diabetes, all of which have been implicated in the development of biliary tract cancer (BTC). This study examined the hypothesis that sweetened beverage consumption is positively associated with risk of BTC in a prospective study. The study population comprised 70 832 Swedish adults (55.9% men, age 45-83 years) from the Swedish Mammography Cohort and Cohort of Swedish Men who were free of cancer and diabetes and completed a food frequency questionnaire at baseline. Incident BTC case patients were ascertained through linkage with the Swedish Cancer Register. Cox proportional hazards regression model was used to analyze the data. All statistical tests were two-sided. During a mean follow-up of 13.4 years, 127 extrahepatic BTC case patients (including 71 gallbladder cancers) and 21 intrahepatic BTC case patients were ascertained. After adjustment for other risk factors, women and men in the highest category of combined sugar-sweetened and artificially sweetened beverage consumption had a statistically significantly increased risk of extrahepatic BTC and gallbladder cancer. The multivariable hazard ratios for two or more servings per day (200 mL/serving) of sweetened beverages compared with no consumption were 1.79 (95% confidence interval [CI] = 1.02 to 3.13) for extrahepatic BTC and 2.24 (95% CI = 1.02 to 4.89) for gallbladder cancer. The corresponding hazard ratio for intrahepatic BTC was 1.69 (95% CI = 0.41 to 7.03). These findings support the hypothesis that high consumption of sweetened beverages may increase the risk of BTC, particularly gallbladder cancer.


Exploring emotional expression recognition in aging adults using the Moving Window Technique.
Adult aging is associated with difficulties in recognizing negative facial expressions such as fear and anger. However, happiness and disgust recognition is generally found to be less affected. Eye-tracking studies indicate that the diagnostic features of fearful and angry faces are situated in the upper regions of the face (the eyes), and for happy and disgusted faces in the lower regions (nose and mouth). These studies also indicate age-differences in visual scanning behavior, suggesting a role for attention in emotion recognition deficits in older adults. However, because facial features can be processed extrafoveally, and expression recognition occurs rapidly, eye-tracking has been questioned as a measure of attention during emotion recognition. In this study, the Moving Window Technique (MWT) was used as an alternative to the conventional eye-tracking technology. By restricting the visual field to a moveable window, this technique provides a more direct measure of attention. We found a strong bias to explore the mouth across both age groups. Relative to young adults, older adults focused less on the left eye, and marginally more on the mouth and nose. Despite these different exploration patterns, older adults were most impaired in recognition accuracy for disgusted expressions. Correlation analysis revealed that among older adults, more mouth exploration was associated with faster recognition of both disgusted and happy expressions. As a whole, these findings suggest that in aging there are both attentional differences and perceptual deficits contributing to less accurate emotion recognition.


Who gets recruited in mild traumatic brain injury research?
Selection bias, common in traumatic brain injury research, limits the clinical usefulness and generalizability of study findings. The purpose of this study was to examine the effect of different inclusion and exclusion criteria on patient enrollment, and the implications for generalizability, in a mild traumatic brain injury (MTBI) study. The study was conducted at the emergency department (ED) of Tampere University Hospital. Our aim was to study outcome from MTBI in patients who do not have pre-existing conditions or other confounding factors. For this, all consecutive patients with acute head trauma (n=1344) were screened. The study design included three inclusion criteria and nine exclusion criteria. The World Health Organization Collaborating Center for Neurotrauma Task Force criteria for MTBI were used. Of all patients screened, 934 (69.5%) fulfilled the MTBI criteria. For those fulfilling the MTBI criteria, various inclusion and exclusion criteria were applied in order to yield those eligible for the outcome study. Applying these criteria excluded 95.1% of MTBI patients, leaving only 46 patients in the final sample. The final sample and the excluded patients with MTBI significantly differed in age, mechanism of injury, and injury severity characteristics. Many studies recruit fundamentally biased samples that are not generalizable to the population of persons who sustain an MTBI. Studying carefully selected samples is often necessary to address specific research questions, but such studies have serious limitations in terms of translating research findings into clinical practice.


Qigong Training Positively Impacts Both Posture and Mood in Breast Cancer Survivors With Persistent Post-surgical Pain: Support for an Embodied Cognition Paradigm.
Theories of embodied cognition hypothesize interdependencies between psychological well-being and physical posture. The purpose of this study was to assess the feasibility of objectively measuring posture, and to explore the relationship between posture and affect and other patient centered outcomes in breast cancer survivors (BCS) with persistent postsurgical pain (PPSP) over a 12-week course of therapeutic Qigong mind-body training. Twenty-one BCS with PPSP attended group Qigong training. Clinical outcomes were pain, fatigue, self-esteem, anxiety, depression, stress and exercise self-efficacy. Posture outcomes were vertical spine and vertical head angles in the sagittal plane, measured with a 3D motion capture system in three conditions: eyes open (EO), eyes open relaxed (EOR) and eyes closed (EC). Assessments were made before and after the Qigong training. The association between categorical variables (angle and mood) was measured by Cramer's V. In the EO condition, most participants who improved in fatigue and anxiety scales also had better vertical head values. For the EOR condition, a moderate correlation was observed between changes in vertical head angle and changes in fatigue scale. In the EC condition, most of the participants who improved in measures of fatigue also improved vertical head angle. Additionally, pain severity decreased while vertical spine angle improved. These preliminary findings support that emotion and other patient centered outcomes should be considered within an embodied framework, and that Qigong may be a promising intervention for addressing biopsychosocially complex interventions such as PPSP in BCSs.


[Diagnostic significance of tumor markers for gynecologic malignancies].
Gynecologic malignancies include ovarian cancer, uterine cervical cancer, endometrial cancer, and trophoblastic neoplasms. With ovarian tumors, due to their location within the abdominal cavity, it is difficult to make a preoperative pathological diagnosis of cancer without laparotomy. From this point of view, the use of tumor markers that consist of carbohydrate antigens, such as CA 125, in addition to diagnostic imaging are useful in the diagnosis of ovarian cancer. SCC antigen, a marker for squamous cell carcinoma, is clinically useful in the management of advanced cervical cancer. At present, there are no useful tumor markers for endometrial cancer that exhibit both high sensitivity and specificity, although CA 125 is often used in clinical practice. Finally, human chorionic gonadotropin (hCG) serves as an ideal tumor marker for trophoblastic disease; however, the incidence of trophoblastic neoplasms has decreased dramatically with the incorporation of strict clinical management of post-molar disease as well as with the overall decrease in the number of pregnancies.


Substance P in the central nervous system.
A radioimmunoassay has been developed for measuring substance P-like immunoreactivity. Assay sensitivity was 0.7fmoles of substance P. Using the radioimmunoassay substance P-like immunoreactivity was detected in postmortem tissue samples from the central nervous system of rats and humans. Immunofluorescence studies confirmed the localisation of substance P in the dorsal horn of the spinal cord.


Lack of protection against oxygen toxicity by in vivo protective agents in the isolated toad bladder.
Agents which protect against the development of oxygen toxicity in vivo were tested in an in vitro system, the isolated urinary bladder of the toad Bufo marinus. None of the agents protected against the inhibition of sodium transport across the bladder by hyperbaric oxygen exposure. Two protective agents, disulfiram and diethyldithiocarbamic acid, significantly increased the rate and extent of sodium transport inhibition by 5 ATA of oxygen, either when added in vitro or given in vivo. It was concluded that oxygen toxicity protective agents may have a nonspecific action in vivo.


Development of cardiovascular function in the horse fetus.
In mammals, the mechanisms regulating an increase in fetal arterial blood pressure with advancing gestational age remain unidentified. In all species studied to date, the prepartum increase in fetal plasma cortisol has an important role in the maturation of physiological systems essential for neonatal survival. In the horse, the prepartum elevation in fetal cortisol and arterial blood pressure are delayed relative to other species. Hence, the mechanisms governing the ontogenic increase in arterial blood pressure in the horse fetus may mature much closer to term than in other fetal animals. In the chronically instrumented pony mare and fetus, this study investigated how changes in fetal peripheral vascular resistance, in plasma concentrations of noradrenaline, adrenaline and vasopressin, and in the maternal-to-fetal plasma concentration gradient of oxygen and glucose relate to the ontogenic changes in fetal arterial blood pressure and fetal plasma cortisol concentration as term approaches. The data show that, towards term in the horse fetus, the increase in arterial blood pressure occurs together with reductions in metatarsal vascular resistance, elevations in plasma concentrations of cortisol, vasopressin, adrenaline and noradrenaline, and falls in the fetal : maternal ratio of blood P(a,O(2)) and glucose concentration. Correlation analysis revealed that arterial blood pressure was positively related with plasma concentrations of vasopressin and noradrenaline, but not adrenaline in the fetus, and inversely related to the fetal : maternal ratio of blood P(a,O(2)), but not glucose, concentration. This suggests that increasing vasopressinergic and noradrenergic influences as well as changes in oxygen availability to the fetus and uteroplacental tissues may contribute to the ontogenic increase in fetal arterial blood pressure towards term in the horse.


The effect of high-polyphenol extra virgin olive oil on cardiovascular risk factors: A systematic review and meta-analysis.
The polyphenol fraction of extra-virgin olive oil may be partly responsible for its cardioprotective effects. The aim of this systematic review and meta-analysis was to evaluate the effect of high versus low polyphenol olive oil on cardiovascular disease (CVD) risk factors in clinical trials. In accordance with PRISMA guidelines, CINAHL, PubMed, Embase and Cochrane databases were systematically searched for relevant studies. Randomized controlled trials that investigated markers of CVD risk (e.g. outcomes related to cholesterol, inflammation, oxidative stress) were included. Risk of bias was assessed using the Jadad scale. A meta-analysis was conducted using clinical trial data with available CVD risk outcomes. Twenty-six studies were included. Compared to low polyphenol olive oil, high polyphenol olive oil significantly improved measures of malondialdehyde (MD: -0.07µmol/L [95%CI: -0.12, -0.02µmol/L]; I2: 88%; p = 0.004), oxidized LDL (SMD: -0.44 [95%CI: -0.78, -0.10µmol/L]; I2: 41%; P = 0.01), total cholesterol (MD 4.5 mg/dL [95%CI: -6.54, -2.39 mg/dL]; p<0.0001) and HDL cholesterol (MD 2.37 mg/dL [95%CI: 0.41, 5.04 mg/dL]; p = 0.02). Subgroup analyses and individual studies reported additional improvements in inflammatory markers and blood pressure. Most studies were rated as having low-to-moderate risk of bias. High polyphenol oils confer some CVD-risk reduction benefits; however, further studies with longer duration and in non-Mediterranean populations are required.


Associations between obesity candidate gene polymorphisms (fat mass and obesity-associated (FTO), melanocortin-4 receptor (MC4R), leptin (LEP) and leptin receptor (LEPR)) and dietary intake in pregnant women.
Genetic variants associated with dietary intake may be important as factors underlying the development of obesity. We investigated the associations between the obesity candidate genes (fat mass and obesity-associated (FTO), melanocortin-4 receptor (MC4R), leptin (LEP) and leptin receptor) and total energy intake and percentage of energy from macronutrients and ultra-processed foods before and during pregnancy. A sample of 149 pregnant women was followed up in a prospective cohort in Rio de Janeiro, Brazil. A FFQ was administered at 5-13 and 30-36 weeks of gestation. Genotyping was performed using real-time PCR. Associations between polymorphisms and the outcomes were investigated through multiple linear regression and ANCOVA having pre-pregnancy dietary intake as a covariate. The A-allele of FTO-rs9939609 was associated with a -6·5 % (95 % CI -12·3, -0·4) decrease in the percentage of energy from protein and positively associated with the percentage of energy from carbohydrates before pregnancy (β=2·6; 95 % CI 0·5, 4·8) and with a 13·3 % (95 % CI 0·7, 27·5) increase in the total energy intake during pregnancy. The C-allele of MC4R-rs17782313 was associated with a -7·6 % (95 % CI -13·8, -1·0) decrease in the percentage of energy from protein, and positively associated with the percentage of energy from ultra-processed foods (β=5·4; 95 % CI 1·1, 9·8) during pregnancy. ANCOVA results revealed changes in dietary intake from pre-pregnancy to pregnancy for FTO-rs9939609 (percentage of energy from ultra-processed foods, P=0·03), MC4R-rs17782313 (total energy intake, P=0·02) and LEP-rs7799039 (total energy intake, P=0·04; percentage of energy from protein, P=0·04). These findings suggest significant associations between FTO-rs9939609, MC4R-rs17782313 and LEP-rs7799039 genes and the components of dietary intake in pregnant women.


Green synthesis of water splitting electrocatalysts: IrO2 nanocages via Pearson's chemistry.
Highly porous iridium oxide structures are particularly well-suited for the preparation of porous catalyst layers needed in proton exchange membrane water electrolyzers. Herein, we report the formation of iridium oxide nanostructured cages, via a water-based process performed at room temperature, using cheap Cu2O cubes as the template. In this synthetic approach, based on Pearson's hard and soft acid-base theory, the replacement of the Cu2O core by an iridium shell is permitted by the difference in hardness/softness of cations and anions of the two reactants Cu2O and IrCl3. Calcination followed by acid leaching allow the removal of residual copper oxide cores and leave IrO2 hierarchical porous structures with outstanding activity toward the oxygen evolution reaction. Fundamental understanding of the reaction steps and identification of the intermediates are permitted by coupling a set of ex situ and in situ techniques including operando time-resolved X-ray absorption spectroscopy during the synthesis.


An electrochemical thermal transistor.
The ability to actively regulate heat flow at the nanoscale could be a game changer for applications in thermal management and energy harvesting. Such a breakthrough could also enable the control of heat flow using thermal circuits, in a manner analogous to electronic circuits. Here we demonstrate switchable thermal transistors with an order of magnitude thermal on/off ratio, based on reversible electrochemical lithium intercalation in MoS2 thin films. We use spatially-resolved time-domain thermoreflectance to map the lithium ion distribution during device operation, and atomic force microscopy to show that the lithiated state correlates with increased thickness and surface roughness. First principles calculations reveal that the thermal conductance modulation is due to phonon scattering by lithium rattler modes, c-axis strain, and stacking disorder. This study lays the foundation for electrochemically-driven nanoscale thermal regulators, and establishes thermal metrology as a useful probe of spatio-temporal intercalant dynamics in nanomaterials.


Cost of treatment for breast cancer in central Vietnam.
In recent years, cases of breast cancer have been on the rise in Vietnam. To date, there has been no study on the financial burden of the disease. This study estimates the direct medical cost of a 5-year treatment course for women with primary breast cancer in central Vietnam. Retrospective patient-level data from medical records at the Hue Central Hospital between 2001 and 2006 were analyzed. Cost analysis was conducted from the health care payers' perspective. Various direct medical cost categories were computed for a 5-year treatment course for patients with breast cancer. Costs, in US dollars, discounted at a 3% rate, were converted to 2010 after adjusting for inflation. For each cost category, the mean, standard deviation, median, and cost range were estimated. Median regression was used to investigate the relationship between costs and the stage, age at diagnosis, and the health insurance coverage of the patients. The total direct medical cost for a 5-year treatment course for breast cancer in central Vietnam was estimated at $975 per patient (range: $11.7-$3,955). The initial treatment cost, particularly the cost of chemotherapy, was found to account for the greatest proportion of total costs (64.9%). Among the patient characteristics studied, stage at diagnosis was significantly associated with total treatment costs. Patients at later stages of breast cancer did not differ significantly in their total costs from those at earlier stages however, but their survival time was much shorter. The absence of health insurance was the main factor limiting service uptake. From the health care payers' perspective, the Government subsidization of public hospital charges lowered the direct medical costs of a 5-year treatment course for primary breast cancer in central Vietnam. However, the long treatment course was significantly influenced by out-of-pocket payments for patients without health insurance.


CO2 assimilation strategies in stratified lakes: Diversity and distribution patterns of chemolithoautotrophs.
While mechanisms of different carbon dioxide (CO2 ) assimilation pathways in chemolithoautotrohic prokaryotes are well understood for many isolates under laboratory conditions, the ecological significance of diverse CO2 fixation strategies in the environment is mostly unexplored. Six stratified freshwater lakes were chosen to study the distribution and diversity of the Calvin-Benson-Bassham (CBB) cycle, the reductive tricarboxylic acid (rTCA) cycle, and the recently discovered archaeal 3-hydroxypropionate/4-hydroxybutyrate (HP/HB) pathway. Eleven primer sets were used to amplify and sequence genes coding for selected key enzymes in the three pathways. Whereas the CBB pathway with different forms of RubisCO (IA, IC and II) was ubiquitous and related to diverse bacterial taxa, encompassing a wide range of potential physiologies, the rTCA cycle in Epsilonproteobacteria and Chloribi was exclusively detected in anoxic water layers. Nitrifiying Nitrosospira and Thaumarchaeota, using the rTCA and HP/HB cycle respectively, are important residents in the aphotic and (micro-)oxic zone of deep lakes. Both taxa were of minor importance in surface waters and in smaller lakes characterized by an anoxic hypolimnion. Overall, this study provides a first insight on how different CO2 fixation strategies and chemical gradients in lakes are associated to the distribution of chemoautotrophic prokaryotes with different functional traits.


Model-based exposure-response analysis to quantify age related differences in the response to scopolamine in healthy subjects.
Subjects with increasing age are more sensitive to the effects of the anti-muscarinic agent scopolamine, which is used (among other indications) to induce temporary cognitive dysfunction in early phase drug studies with cognition enhancing compounds. The enhanced sensitivity has always been attributed to incipient cholinergic neuronal dysfunction, as a part of the normal aging process. The aim of the study was to correlate age-dependent pharmacodynamic neuro-physiologic effects of scopolamine after correcting for differences in individual exposure. We applied a pharmacokinetic and pharmacodynamic modelling approach to describe individual exposure and neurocognitive effects of intravenous scopolamine administration in healthy subjects. A two-compartment linear kinetics model best described the plasma concentrations of scopolamine. The estimated scopolamine population mean apparent central and peripheral volume of distribution was 2.66 ± 1.050 l and 62.10 ± 10.100 l, respectively and the clearance was 1.09 ± 0.096 l min(-1) . Age was not related to a decrease of performance in the tests following scopolamine administration in older subjects. Only the saccadic peak velocity showed a positive correlation between age and sensitivity to scopolamine. Age was, however, correlated at baseline with an estimated slower reaction time while performing the cognitive tests and to higher global δ and frontal θ frequency bands measured with the surface EEG. Most of the differences in response to scopolamine administration between young and older subjects could be explained by pharmacokinetic differences (lower clearance) and not to an enhanced sensitivity when corrected for exposure levels.


Stem cells treatment for sciatic nerve injury.
Sciatic nerve injury is common and usually results in degeneration of the distal axons and muscle denervation. Chronic muscle atrophy and fibrosis limit the recovery of muscle function and severely compromises efforts to restore muscle function. Despite early diagnosis and modern surgical techniques there is still poor functional recovery. Stem cell transplantation has been investigated as a promising treatment strategy for peripheral nerve injury, and has demonstrated utility in limiting neuronal damage. The focus has been on the isolation of stem cells from bone-marrow and adipose tissue in addition to embryonic and neuronal stem cells. Transplantation of these cells into transected sciatic nerve in animal models demonstrates clinical improvement, inducing vigorous nerve regeneration accompanied by myelin synthesis. Cell replacement, trophic factor production, extracellular matrix molecule synthesis, guidance, remyelination, microenvironmental stabilization and immune modulation have been postulated as possible mechanisms for stem cell implantation. Although further research is still needed, this therapeutic approach will probably become a routine treatment technique in the coming years, especially with bone marrow mesenchymal stem cells. We believe that the most promising results were noted for the use of stem cells of this origin in the treatment of sciatic nerve injury.


Towards greener and more sustainable batteries for electrical energy storage.
Ever-growing energy needs and depleting fossil-fuel resources demand the pursuit of sustainable energy alternatives, including both renewable energy sources and sustainable storage technologies. It is therefore essential to incorporate material abundance, eco-efficient synthetic processes and life-cycle analysis into the design of new electrochemical storage systems. At present, a few existing technologies address these issues, but in each case, fundamental and technological hurdles remain to be overcome. Here we provide an overview of the current state of energy storage from a sustainability perspective. We introduce the notion of sustainability through discussion of the energy and environmental costs of state-of-the-art lithium-ion batteries, considering elemental abundance, toxicity, synthetic methods and scalability. With the same themes in mind, we also highlight current and future electrochemical storage systems beyond lithium-ion batteries. The complexity and importance of recycling battery materials is also discussed.


Resonant transport in Nb /GaAs /AlGaAs heterostructures: realization of the de Gennes-Saint-James model.
Resonant transport is demonstrated in a hybrid superconductor-semiconductor heterostructure junction grown by molecular beam epitaxy on GaAs. This heterostructure realizes the model system introduced by de Gennes and Saint-James in 1963 [P. G. de Gennes and D. Saint-James, Phys. Lett. 4, 151 (1963)]. At low temperatures a single marked resonance peak is shown superimposed to the characteristic Andreev-dominated subgap conductance. The observed magnetotransport properties are successfully analyzed within the random matrix theory of quantum transport, and ballistic effects are included by directly solving the Bogoliubov-de Gennes equations.


The value of magnetic resonance imaging in the evaluation of fatty filum terminale.
To determine whether there are magnetic resonance imaging (MRI) characteristics of fatty fila that are correlated with neurological deficits, especially in the presence of a normal-level conus medullaris. Lumbosacral MRI scans were reviewed for patients with fatty fila who were treated at Duke University Medical Center during a 5-year period. The patients were divided into three groups. Group I patients (n = 5) had fatty fila that were incidentally detected during evaluations for metastases or infections. Group II patients (n = 16) exhibited isolated low back pain but were in neurologically intact condition. Group III patients (n = 15) exhibited neurological impairments consistent with distal spinal cord dysfunction. Several characteristics were measured on the MRI scans, including the location of the conus medullaris, the filum thickness, and the distance of fat from the conus. These results were assessed for statistically significant correlation with the presence of clinical symptoms. The majority of patients in all three groups demonstrated the normal conus position (L2 or above) and thickened fila. The distance of fat from the conus was the only parameter that demonstrated a statistically significant difference among the groups. The following findings were noted: 1) patients were likely to exhibit neurological deficits at a younger age (<22 yr in Group III versus 47 yr in Groups I and II); 2) a conus level below L2 was associated with neurological deficits (Group III); 3) filum thickness was not correlated with clinical presentation; 4) fat in the filum within 13 mm of the conus medullaris was most predictive of neurological deficits (Group III).


Genetic and epidemiological studies of dengue type 2 viruses by hybridization using synthetic deoxyoligonucleotides as probes.
A rapid nucleic acid hybridization procedure was developed for examining the genotypic variation of dengue type 2 viruses (DEN 2) having distinct RNase T1 fingerprints and isolated from different geographical areas. Synthetic DNA hybridization probes were constructed complementary in nucleotide sequence to common and unique RNase T1 oligonucleotides of topotype viruses from Puerto Rico/South Pacific, Jamaica, the Seychelles, Thailand/Burma and Africa. Hybridization probes with both type- and topotype-specific reactivities were observed, as were probes specific for two or more of the DEN 2 topotypes. These results confirm geographical movement of topotype virus strains and suggest possible origins. Detection of DEN 2 RNA by hybridization is a rapid and reproducible method that can be modified and applied as a viable alternative to the laborious T1 oligonucleotide fingerprinting.


Two types of cells with central innervation in pineal gland of guinea pigs.
Cells within pineal glands isolated from young, male guinea pigs were impaled with intracellular microelectrodes and their responses to stimulate the nerve supply to the gland were studied. Two types of cells were identified. The response of cells of type I was a depolarization on which spikes were superimposed. Blockers of alpha-adrenoceptors abolished the spikes while beta-adrenoceptor blockers reduced the depolarization to 27%, leaving a small tetrodotoxin-sensitive depolarization. After bilateral removal of the superior cervical ganglia (SCG) the beta-mediated depolarization was not observed while the spikes and the smaller depolarization persisted. The response of cells of type II was an initial large, transient depolarization followed by a smaller depolarization. Both components were reversibly blocked by tetrodotoxin. The only agents found to have any effect on these cells were oxytocin, vasopressin, and vasotocin. These peptides caused depolarization similar in amplitude to the larger response to nerve stimulation, although more prolonged. The large depolarization was not observed following ganglionectomy, but the smaller one persisted. It is concluded that cells of type I and II both receive inputs from nerves whose cell bodies lie in the SCG. Cells of both types are also innervated through another pathway.


EVI5 protein associates with the INCENP-aurora B kinase-survivin chromosomal passenger complex and is involved in the completion of cytokinesis.
EVI5 has been shown to be a novel centrosomal protein in interphase cells. In this report, we demonstrate using immunofluorescence microscopy that EVI5 has a dynamic distribution during mitosis, being associated with the mitotic spindle through anaphase and remaining within the midzone and midbody until completion of cytokinesis. Knockdown of EVI5 using siRNA results in a multinucleate phenotype, which is consistent with an essential role for this protein in the completion of cytokinesis. The EVI5 protein also undergoes posttranslational modifications during the cell cycle, which involve phosphorylation in early mitosis and proteolytic cleavage during late mitosis and cytokinesis. Since the subcellular distribution of the EVI5 protein was similar to that characteristic of chromosomal passenger proteins during the terminal stages of cytokinesis, we used immunoprecipitation and GST pull-down approaches to demonstrate that EVI5 is associated with the aurora B kinase protein complex (INCENP, aurora B kinase and survivin). Together, these data provide evidence that EVI5 is an essential component of the protein machinery facilitating the final stages of cell septation at the end of mitosis.


Adherence to Continuous Positive Airway Pressure in Existing Users: Self-Efficacy Enhances the Association between Continuous Positive Airway Pressure and Adherence.
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common sleep disorder associated with a myriad of sequelae. OSAHS is effectively treated with continuous positive airway pressure (CPAP) therapy. However, fewer than 50% of patients are compliant with their CPAP therapy prescriptions. The current study sought to explore an integrated, biopsychological approach to CPAP adherence among experienced CPAP users. We performed a retrospective, cross-sectional analysis of a cohort of veterans with a diagnosis of OSAHS (n = 191) who were prescribed CPAP therapy and returned for adherence download at the Miami VA Sleep Clinic. The relationships between biomedical characteristics (e.g., CPAP pressure, self-reported sleepiness, and change in sleep efficiency) and psychological factors (e.g., self-efficacy beliefs and psychological diagnoses) and objectively measured CPAP use were examined to determine whether psychological factors moderated the relationships between biomedical characteristics and CPAP adherence. Hierarchical regression analyses predicting CPAP adherence (adjusting for time since CPAP prescription, age, education, prescribed CPAP pressure, daytime sleepiness, changes in sleep efficiency with CPAP, and psychiatric conditions) revealed the following: (1) CPAP self-efficacy and CPAP pressure were positively related to adherence, and (2) CPAP self-efficacy moderates the relationship between CPAP pressure and CPAP adherence. There was no relationship between CPAP pressure and adherence in individuals with low self-efficacy beliefs. However, for individuals with high self-efficacy beliefs, there was a significant positive relationship between CPAP pressure and adherence. Self-efficacy beliefs appear to be a prime target for focused interventions aimed at improving CPAP adherence among those individuals with higher pressure prescriptions.