Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics

Sattler S, Mehlkop G, Graeff P, Sauer C. Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics. Substance Abuse Treatment, Prevention, and Policy. 2014;9(1): 8.Background The use of cognitive enhancement (CE) by means of pharmaceutical agents has been the subject of intense debate both among scientists and in the media. This study investigates several drivers of and obstacles to the willingness to use prescription drugs non-medically for augmenting brain capacity. Methods We conducted a web-based study among 2,877 students from randomly selected disciplines at German universities. Using a factorial survey, respondents expressed their willingness to take various hypothetical CE-drugs; the drugs were described by five experimentally varied characteristics and the social environment by three varied characteristics. Personal characteristics and demographic controls were also measured. Results We found that 65.3% of the respondents staunchly refused to use CE-drugs. The results of a multivariate negative binomial regression indicated that respondents’ willingness to use CE-drugs increased if the potential drugs promised a significant augmentation of mental capacity and a high probability of achieving this augmentation. Willingness decreased when there was a high probability of side effects and a high price. Prevalent CE-drug use among peers increased willingness, whereas a social environment that strongly disapproved of these drugs decreased it. Regarding the respondents’ characteristics, pronounced academic procrastination, high cognitive test anxiety, low intrinsic motivation, low internalization of social norms against CE-drug use, and past experiences with CE-drugs increased willingness. The potential severity of side effects, social recommendations about using CE-drugs, risk preferences, and competencies had no measured effects upon willingness. Conclusions These findings contribute to understanding factors that influence the willingness to use CE-drugs. They support the assumption of instrumental drug use and may contribute to the development of prevention, policy, and educational strategies

Downregulation of Cinnamyl-Alcohol Dehydrogenase in Switchgrass by RNA Silencing Results in Enhanced Glucose Release after Cellulase Treatment

Cinnamyl alcohol dehydrogenase (CAD) catalyzes the last step in monolignol biosynthesis and genetic evidence indicates CAD deficiency in grasses both decreases overall lignin, alters lignin structure and increases enzymatic recovery of sugars. To ascertain the effect of CAD downregulation in switchgrass, RNA mediated silencing of CAD was induced through Agrobacterium mediated transformation of cv. “Alamo” with an inverted repeat construct containing a fragment derived from the coding sequence of PviCAD2. The resulting primary transformants accumulated less CAD RNA transcript and protein than control transformants and were demonstrated to be stably transformed with between 1 and 5 copies of the T-DNA. CAD activity against coniferaldehyde, and sinapaldehyde in stems of silenced lines was significantly reduced as was overall lignin and cutin. Glucose release from ground samples pretreated with ammonium hydroxide and digested with cellulases was greater than in control transformants. When stained with the lignin and cutin specific stain phloroglucinol-HCl the staining intensity of one line indicated greater incorporation of hydroxycinnamyl aldehydes in the lignin

Cellulite and extracorporeal Shockwave therapy (CelluShock-2009) - a Randomized Trial

<p>Abstract</p> <p>Background</p> <p>Cellulite is a widespread problem involving females' buttocks and thighs based on the female specific anatomy. Given the higher number of fat cells stored in female fatty tissue in contrast to males, and the aging process of connective tissue leads to an imbalance between lipogenesis and lipolysis with subsequent large fat cells bulging the skin. In addition, microcirculatory changes have been suggested, however remain largely unknown in a controlled clinical setting. We hypothesize that the combination of extracorporeal shockwave and a daily gluteal muscle strength program is superior to the gluteal muscle strength program alone in cellulite.</p> <p>Methods/Design</p> <p>Study design: Randomized-controlled trial. IRB approval was granted at Hannover Medical School, Germany on May 22, 2009. For allocation of participants, a 1:1 ratio randomization was performed using opaque envelopes for the concealment of allocation. Reporting: according to CONSORT 2010. Eligible patients were females aged 18 or over and 65 or younger with cellulite with documented cellulite 1°-4° according to the Nürnberger score. Exclusion criteria were suspected or evident pregnancy, no cellulite, no informed consent or age under 18 years or above 65 years. Patients were recruited by advertisements in local regional newspapers and via the Internet. Analysis: Intention-to-treat. Outcome parameters: a) Photonumeric severity scale, b) Nürnberger Score, c) circumference measurements, d) capillary blood flow, e) tissue oxygen saturation, f) postcapillary venous blood flow. Intervention group: Six sessions of extracorporeal focused shock wave for six sessions (2000 impulses, 0,25 mJ/m2 every 1-2 weeks) at both gluteal and thigh regions plus a specific gluteal strength exercise training. Control group: Six sessions of sham extracorporeal focused shock wave for six sessions (2000 impulses, 0,01 mJ/m2 every 1-2 weeks) at both gluteal and thigh regions plus a specific gluteal strength exercise training. Follow-up: 12 weeks. Blinding was achieved for all participants enrolled in the trial, the photograph taking the digital images for the primary outcome measure, the two assessors of the outcome measures, all additional health care providers and for the analyst from the biometrical department. Only one researcher (BJ) was aware of the group assignment performing the randomisation and the extracorporeal shock wave therapy.</p> <p>Discussion</p> <p>This randomised-controlled trial will provide much needed evidence on the clinical effectiveness of focused extracorporal shock wave therapy as an adjunct to gluteal strength training in females suffering cellulite.</p> <p>ClinicalTrials.gov identifier</p> <p>NCT00947414</p

Comparative evaluation of the Ifakara tent trap-B, the standardized resting boxes and the human landing catch for sampling malaria vectors and other mosquitoes in urban Dar es Salaam, Tanzania

BACKGROUND\ud \ud Frequent, sensitive and accurate sampling of Anopheles mosquitoes is a prerequisite for effective management of malaria vector control programmes. The most reliable existing means to measure mosquito density is the human landing catch (HLC). However, the HLC technique raises major ethical concerns because of the necessity to expose humans to vectors of malaria and a variety of other pathogens. Furthermore, it is a very arduous undertaking that requires intense supervision, which is severely limiting in terms of affordability and sustainability.\ud \ud METHODS\ud \ud A community-based, mosquito sampling protocol, using the Ifakara tent trap-B (ITT-B) and standardized resting boxes (SRB), was developed and evaluated in terms of the number and sample composition of mosquitoes caught by each, compared to rigorously controlled HLC. Mosquitoes were collected once and three times every week by the HLC and the alternative methods, respectively, in the same time and location.\ud \ud RESULTS\ud \ud Overall, the three traps caught 44,848 mosquitoes. The ITT-B, HLC and SRB caught 168, 143 and 46 Anopheles gambiae s.l. as well as 26,315, 13,258 and 4,791 Culex species respectively. The ITT-B was three- and five-times cheaper than the HLC per mosquito caught for An. gambiae and Cx. Species, respectively. Significant correlations between the numbers caught by HLC and ITT-B were observed for both An. gambiae s.l. (P < 0.001) and Cx. species (P = 0.003). Correlation between the catches with HLC and SRB were observed for Cx. species (P < 0.001) but not An. gambiae s.l. (P = 0.195), presumably because of the low density of the latter. Neither ITT-B nor SRB exhibited any obvious density dependence for sampling the two species.\ud \ud CONCLUSION\ud \ud SRBs exhibited poor sensitivity for both mosquito taxa and are not recommended in this setting. However, this protocol is affordable and effective for routine use of the ITT-B under programmatic conditions. Nevertheless, it is recommended that the trap and the protocol be evaluated further at full programmatic scales to establish effectiveness under fully representative conditions of routine practice

Evolving neural network optimization of cholesteryl ester separation by reversed-phase HPLC

Cholesteryl esters have antimicrobial activity and likely contribute to the innate immunity system. Improved separation techniques are needed to characterize these compounds. In this study, optimization of the reversed-phase high-performance liquid chromatography separation of six analyte standards (four cholesteryl esters plus cholesterol and tri-palmitin) was accomplished by modeling with an artificial neural network–genetic algorithm (ANN-GA) approach. A fractional factorial design was employed to examine the significance of four experimental factors: organic component in the mobile phase (ethanol and methanol), column temperature, and flow rate. Three separation parameters were then merged into geometric means using Derringer’s desirability function and used as input sources for model training and testing. The use of genetic operators proved valuable for the determination of an effective neural network structure. Implementation of the optimized method resulted in complete separation of all six analytes, including the resolution of two previously co-eluting peaks. Model validation was performed with experimental responses in good agreement with model-predicted responses. Improved separation was also realized in a complex biological fluid, human milk. Thus, the first known use of ANN-GA modeling for improving the chromatographic separation of cholesteryl esters in biological fluids is presented and will likely prove valuable for future investigators involved in studying complex biological samples

Plasma sphingosine-1-phosphate is elevated in obesity

Background: Dysfunctional lipid metabolism is a hallmark of obesity and insulin resistance and a risk factor for various cardiovascular and metabolic complications. In addition to the well known increase in plasma triglycerides and free fatty acids, recent work in humans and rodents has shown that obesity is associated with elevations in the bioactive class of sphingolipids known as ceramides. However, in obesity little is known about the plasma concentrations of sphinogsine-1-phosphate (S1P), the breakdown product of ceramide, which is an important signaling molecule in mammalian biology. Therefore, the purpose of this study was to examine the impact of obesity on circulating S1P concentration and its relationship with markers of glucose metabolism and insulin sensitivity. Methodology/Principal Findings: Plasma S1P levels were determined in high-fat diet (HFD)-induced and genetically obese (ob/ob) mice along with obese humans. Circulating S1P was elevated in both obese mouse models and in obese humans compared with lean healthy controls. Furthermore, in humans, plasma S1P positively correlated with total body fat percentage, body mass index (BMI), waist circumference, fasting insulin, HOMA-IR, HbA1c (%), total and LDL cholesterol. In addition, fasting increased plasma S1P levels in lean healthy mice. Conclusion: We show that elevations in plasma S1P are a feature of both human and rodent obesity and correlate with metabolic abnormalities such as adiposity and insulin resistance

Cooperative Interaction of Transcription Termination Factors with the RNA Polymerase II C-terminal Domain

Phosphorylation of the C-terminal domain of RNA polymerase II controls the co-transcriptional assembly of RNA processing and transcription factors. Recruitment relies on conserved CTDinteracting domains that recognize different CTD phosphoisoforms during the transcription cycle, but the molecular basis for their specificity remains unclear. We show that the CTD-interacting domains of two transcription termination factors, Rtt103 and Pcf11, achieve high affinity and specificity both by specifically recognizing the phosphorylated CTD and by cooperatively binding to neighboring CTD repeats. Single amino acid mutations at the protein-protein interface abolish cooperativity and affect recruitment at the 3′-end processing site in vivo. We suggest that this cooperativity provides a signal-response mechanism to ensure that its action is confined only to proper polyadenylation sites where Serine 2 phosphorylation density is highest

Modelling the impact of vector control interventions on Anopheles gambiae population dynamics

<p>Abstract</p> <p>Background</p> <p>Intensive anti-malaria campaigns targeting the <it>Anopheles </it>population have demonstrated substantial reductions in adult mosquito density. Understanding the population dynamics of <it>Anopheles </it>mosquitoes throughout their whole lifecycle is important to assess the likely impact of vector control interventions alone and in combination as well as to aid the design of novel interventions.</p> <p>Methods</p> <p>An ecological model of <it>Anopheles gambiae sensu lato </it>populations incorporating a rainfall-dependent carrying capacity and density-dependent regulation of mosquito larvae in breeding sites is developed. The model is fitted to adult mosquito catch and rainfall data from 8 villages in the Garki District of Nigeria (the 'Garki Project') using Bayesian Markov Chain Monte Carlo methods and prior estimates of parameters derived from the literature. The model is used to compare the impact of vector control interventions directed against adult mosquito stages - long-lasting insecticide treated nets (LLIN), indoor residual spraying (IRS) - and directed against aquatic mosquito stages, alone and in combination on adult mosquito density.</p> <p>Results</p> <p>A model in which density-dependent regulation occurs in the larval stages via a linear association between larval density and larval death rates provided a good fit to seasonal adult mosquito catches. The effective mosquito reproduction number in the presence of density-dependent regulation is dependent on seasonal rainfall patterns and peaks at the start of the rainy season. In addition to killing adult mosquitoes during the extrinsic incubation period, LLINs and IRS also result in less eggs being oviposited in breeding sites leading to further reductions in adult mosquito density. Combining interventions such as the application of larvicidal or pupacidal agents that target the aquatic stages of the mosquito lifecycle with LLINs or IRS can lead to substantial reductions in adult mosquito density.</p> <p>Conclusions</p> <p>Density-dependent regulation of anopheline larvae in breeding sites ensures robust, stable mosquito populations that can persist in the face of intensive vector control interventions. Selecting combinations of interventions that target different stages in the vector's lifecycle will result in maximum reductions in mosquito density.</p

Skewed Exposure to Environmental Antigens Complements Hygiene Hypothesis in Explaining the Rise of Allergy

The Hygiene Hypothesis has been recognized as an important cornerstone to explain the sudden increase in the prevalence of asthma and allergic diseases in modernized culture. The recent epidemic of allergic diseases is in contrast with the gradual implementation of Homo sapiens sapiens to the present-day forms of civilization. This civilization forms a gradual process with cumulative effects on the human immune system, which co-developed with parasitic and commensal Helminths. The clinical manifestation of this epidemic, however, became only visible in the second half of the twentieth century. In order to explain these clinical effects in terms of the underlying IgE-mediated reactions to innocuous environmental antigens, the low biodiversity of antigens in the domestic environment plays a pivotal role. The skewing of antigen exposure as a cumulative effect of reducing biodiversity in the immediate human environment as well as in changing food habits, provides a sufficient and parsimonious explanation for the rise in allergic diseases in a highly developed and helminth-free modernized culture. Socio-economic tendencies that incline towards a further reduction of environmental biodiversity may provide serious concern for future health. This article explains that the “Hygiene Hypothesis”, the “Old Friends Hypothesis”, and the “Skewed Antigen Exposure Hypothesis” are required to more fully explain the rise of allergy in modern societies

Ordered hierarchy versus scale invariance in sequence stratigraphy

200 x 10(6) years) are symmetrical transgressive- regressive cycles. However, the sequence record in the range of 1 x 10(4)-200 x 10(6) years, the principal domain of sequence stratigraphy, shows a rather irregular succession of sequences with variable symmetry and bounded by flooding surfaces or exposure surfaces. For these time scales, scale-invariant models are a good first approximation, particularly because the evidence for scale-invariance and randomness in the stratigraphic record is strong: Frequency spectra of sea-level change as well as rates of sedimentation and rates of accommodation change plotted against length of observation span show basic trends indistinguishable from random walk. These trends, combined with scale-invariant sequence models may be the most efficient tools for across-the-board predictions on sequences and for locating islands of order in the sequence record