Advances in understanding the molecular basis of the first steps in color vision

Serving as one of our primary environmental inputs, vision is the most sophisticated sensory system in humans. Here, we present recent findings derived from energetics, genetics and physiology that provide a more advanced understanding of color perception in mammals. Energetics of cis–trans isomerization of 11-cis-retinal accounts for color perception in the narrow region of the electromagnetic spectrum and how human eyes can absorb light in the near infrared (IR) range. Structural homology models of visual pigments reveal complex interactions of the protein moieties with the light sensitive chromophore 11-cis-retinal and that certain color blinding mutations impair secondary structural elements of these G protein-coupled receptors (GPCRs). Finally, we identify unsolved critical aspects of color tuning that require future investigation.     

A personalized systems medicine approach to refractory rumination

Rationale, aims and objectives As with many functional disorders, rumination syndrome poses a great dilemma when approached via standard of care. This case report illustrates how rumination syndrome may be effectively approached using the systems medicine. Method The patient's treatment involved two distinctively different treatment cycles. Initially she was treated in an academic tertiary inpatient and outpatient multidisciplinary program with a primary symptom‐based focus with little improvement. She subsequently sought care at a systems‐based integrative medicine clinic within an academic family medicine centre, which identified the inciting events, diagnosed the current pathology and developed a stepwise treatment plan. Results The patient is now rumination free. Conclusion Chronic or refractory diseases, especially when regarded as ‘functional’ may be approached by a systems medicine methodology, which allows physicians to fine‐tune the vast amount of specific pieces of knowledge to achieve an integrated approach to managing the whole person.     

Design of robust nonfragile H∞ controller for uncertain nonlinear polynomial systems

This paper is concerned with the robust H_∞ nonfragile controller design for a particular class of nonlinear systems, namely, the perturbed polynomial systems, which are subject to unstructured bounded uncertainties in both the system model and the control law. Combining the Lyapunov stability theory, properties of linear matrix inequality, and Kronecker product properties, a sufficient condition of robust H_∞ nonfragile control design is proposed. More specifically, we propose a robust H_∞ controller of nonlinear polynomial systems with additive unstructured uncertainties and variation in the control law itself that guarantee the stability and the attenuation of external perturbations. Two examples are provided to illustrate the effectiveness of the proposed approach.     

Comparison of invasively measured FFR with FFR derived from coronary CT angiography for detection of lesion-specific ischemia: Results from a PC-based prototype algorithm

BackgroundWe evaluated the diagnostic accuracy of a novel prototype for on-site determination of CT-based FFR (cFFR) on a standard personal computer (PC) compared to invasively measured FFR in patients with suspected coronary artery disease.MethodsA total of 91 vessels in 71 patients (mean age 65 ± 9 years) in whom coronary CT angiography had been performed due to suspicion of coronary artery disease, and who subsequently underwent invasive coronary angiography with FFR measurement were analyzed. For both cFFR and FFR, a threshold of ≤0.80 was used to indicate a hemodynamically relevant stenosis. The mean time needed to calculate cFFR was 12.4 ± 3.4 min. A very close correlation between cFFR and FFR could be shown (r = 0.85; p < 0.0001) with Bland-Altman analysis showing moderate agreement between FFR and cFFR with mild systematic overestimation of FFR values in CT (mean difference 0.0049, 95% limits of agreement ±2SD −0.007 to 0.008). Compared to FFR, the sensitivity of cFFR to detect hemodynamically significant lesions was 91% (19/21, 95% CI: 70%–99%), specificity was 96% (67/70, 95% CI: 88%–99%), positive predictive value 86% (95% CI: 65%–97%) and negative predictive value was 97% (95% CI: 90%–100%) with an accuracy of 93%.ConclusioncFFR obtained using an on-site algorithm implemented on a standard PC shows high diagnostic accuracy to detect lesions causing ischemia as compared to FFR. Importantly, the time needed for analysis is short which may be useful for improving clinical workflow.     

Praziquantel treatment of school children from single and mixed infection foci of intestinal and urogenital schistosomiasis along the Senegal River Basin: monitoring treatment success and re-infection patterns

Following major water development schemes in the 1980s, schistosomiasis has become a serious parasitic disease of children living in the Senegal River Basin. Both urogenital (Schistosoma haematobium) and intestinal (Schistosoma mansoni) schistosomiasis can be highly prevalent in school-aged children, with many individuals infected with both parasites. In order to investigate the transmission and re-infection dynamics of both parasite species, single and mixed infection foci at three villages (Nder and Temeye; S. mansoni and S. haematobium foci and Guia; S. haematobium focus) were studied. In each focus infected children were identified and selected for a 12-month study involving two treatments with praziquantel (40 mg/kg) three weeks apart at the beginning of the study and again 6 months into the study. Urine and stool samples were examined for schistosome eggs before and at 6 weeks and 6 months after chemotherapy. Prevalence and intensity of infection were recorded for each child at each time point. Before treatment, in all three villages, the prevalence and intensity of infection was extremely high for both S. mansoni (79–100%) and S. haematobium (81–97%). With the first round of chemotherapy sufficient cure rates (CRs) of both species were achieved in all villages (38–96%) with high egg reduction rates (ERRs) (97–99%). The data show that high and rapid re-infection rates occur, especially for S. mansoni, within a six-month period following treatment. Re-infection must be highly linked to ecological and seasonal factors. The persistence of S. mansoni in Nder could raise concern as levels of infection intensity remain high (geometric mean intensity at baseline 653 epg changed to 705 epg at 12 months) after four rounds of chemotherapy. This phenomenon could be explained by extremely rapid re-infection dynamics or a sub-optimal efficacy of praziquantel against S. mansoni in this village. High intensities in mixed infections may influence disease epidemiology and control warranting further studies. The disease situation in the SRB must be monitored closely and new treatment regimes should be designed and implemented to control schistosomiasis in the school-age population.     

Simulation of 125I-based radioprobing experiments to study DNA quadruplex structure and topology

Purpose: Certain guanine-rich DNA sequences have the capacity to fold into four-stranded structures stabilized by the stacking of square planar arrangements of four hydrogen-bonded guanine bases. However both the overall topology of folding and the more detailed three dimensional structure of these quadruplexes is difficult to determine or predict, and they can be polymorphic, altering radically depending on environmental conditions. Radioprobing experiments, in which Auger electrons emitted during the decay of a ¹²⁵I-containing base induce strand cleavage in a distance- and structure-dependent manner, have provided possible means of determining these details. Here we have used a combination of computer simulation methods to study the information obtained by one such experiment, reported in 2004.

Method: Models were constructed of three quadruplex topologies considered in the experiment, and one other topology proposed more recently. Molecular Dynamics simulations were used to equilibrate these structures and monitor how they evolved over several nanoseconds in solution. Snapshots from the trajectories were then subjected to Monte Carlo track structure prediction, from which theoretical cleavage patterns have been extracted.

Results: The four topologies were found to yield quite different cleavage patterns, which allow the presence of particular conformations in an experiment to be predicted.

Conclusion: Radioprobing, which is usable in biologically relevant environments, is sensitive enough to distinguish with some confidence between alternative folding topologies in a DNA structure. Monte Carlo track structure simulation can reinforce or question conclusions drawn from experiment, and Molecular Dynamics used with various restraints provides a practical means of guiding a model towards one that yields cleavage patterns closer to those found experimentally.     

Multi-level Factors Associated with Pregnancy among Urban Adolescent Women Seeking Psychological Services

The purpose of this study was to examine the prevalence of pregnancy as well as multi-level factors (i.e., individual, family, and environment) associated with history of pregnancy among a sample of urban adolescent women seeking psychological services. Data were collected from a total of 264 sexually active, 13–18-year-old, adolescent women who participated in a larger HIV prevention study. Adolescents and one participating parent completed an audio computer-assisted self-interviewing survey. A total of 17.4 % of participants reported a history of pregnancy. A multivariable logistic regression model suggests that after controlling for empirically derived sociodemographic and behavioral covariates, absence of father in the home, family support and cohesion, and neighborhood risk were positively related to pregnancy. This study is among the first to examine multi-level factors associated with pregnancy among adolescent women diagnosed with psychological disorders. Consideration of such factors is crucial both in terms of clinical practice and in the design of pregnancy prevention programs. Collaboration between physicians and mental health providers working with adolescent women is crucial and represents an ideal opportunity to promote parental involvement and access to supportive community resources, including pregnancy prevention programs for this vulnerable population of adolescents.