T1-weighted MRI as a substitute to CT for refocusing planning in MR-guided focused ultrasound.

Precise focusing is essential for transcranial MRI-guided focused ultrasound (TcMRgFUS) to minimize collateral damage to non-diseased tissues and to achieve temperatures capable of inducing coagulative necrosis at acceptable power deposition levels. CT is usually used for this refocusing but requires a separate study (CT) ahead of the TcMRgFUS procedure. The goal of this study was to determine whether MRI using an appropriate sequence would be a viable alternative to CT for planning ultrasound refocusing in TcMRgFUS. We tested three MRI pulse sequences (3D T1 weighted 3D volume interpolated breath hold examination (VIBE), proton density weighted 3D sampling perfection with applications optimized contrasts using different flip angle evolution and 3D true fast imaging with steady state precision T2-weighted imaging) on patients who have already had a CT scan performed. We made detailed measurements of the calvarial structure based on the MRI data and compared those so-called 'virtual CT' to detailed measurements of the calvarial structure based on the CT data, used as a reference standard. We then loaded both standard and virtual CT in a TcMRgFUS device and compared the calculated phase correction values, as well as the temperature elevation in a phantom. A series of Bland-Altman measurement agreement analyses showed T1 3D VIBE as the optimal MRI sequence, with respect to minimizing the measurement discrepancy between the MRI derived total skull thickness measurement and the CT derived total skull thickness measurement (mean measurement discrepancy: 0.025; 95% CL (-0.22-0.27); p = 0.825). The T1-weighted sequence was also optimal in estimating skull CT density and skull layer thickness. The mean difference between the phase shifts calculated with the standard CT and the virtual CT reconstructed from the T1 dataset was 0.08 ± 1.2 rad on patients and 0.1 ± 0.9 rad on phantom. Compared to the real CT, the MR-based correction showed a 1 °C drop on the maximum temperature elevation in the phantom (7% relative drop). Without any correction, the maximum temperature was down 6 °C (43% relative drop). We have developed an approach that allows for a reconstruction of a virtual CT dataset from MRI to perform phase correction in TcMRgFUS.

Elevated resource availability sufficient to turn opportunistic into virulent fish pathogens.

There is mounting evidence that organic or inorganic enrichment of aquatic environments increases the risk of infectious diseases, with disease agents ranging from helminth parasites to fungal, bacterial, and viral pathogens. The causal link between microbial resource availability and disease risk is thought to be complex and, in the case of so-called "opportunistic pathogens," to involve additional stressors that weaken host resistance (e.g., temperature shifts or oxygen deficiencies). In contrast to this perception, our experiment shows that the link between resource levels and infection of fish embryos can be very direct: increased resource availability can transform benign microbial communities into virulent ones. We find that embryos can be harmed before further stresses (e.g., oxygen depletion) weaken them, and treatment with antibiotics and fungicides cancels the detrimental effects. The changed characteristics of symbiotic microbial communities could simply reflect density-dependent relationships or be due to a transition in life-history strategy. Our findings demonstrate that simple microhabitat changes can be sufficient to turn "opportunistic" into virulent pathogens.

Comment faciliter la consommation de protéines après un bypass gastrique [How to facilitate protein consumption after gastric bypass?].

After a gastric bypass, covering protein needs is impossible. This deficit is co-responsible for several postoperative complications so it is essential to inform, prepare and train every patient candidate for such an intervention. To increase protein intake, it is important to work on two different aspects: on the one hand on food sources, targeting the richest food and, on the other hand, on food tolerance so that these foods can be consumed. In fact, gastric bypass induces not only a reduction in gastric volume, but also reduces the passage from the stomach to the intestine. Changes in feeding behavior are much needed to improve food tolerance.

Switch-peptides: From conformational studies to Alzheimer's disease

Studies on designed peptides that exhibit high tendencies for medium-induced conformational transitions have recently attracted much attention because structural changes are considered as molecular key processes in degenerative diseases. The experimental access to these events has been limited so far mainly due to the intrinsic tendency of the involved polypeptides for self-association and aggregation, e.g. amyloid P plaque formation, thought to be at the origin of Alzheimer's disease. We have developed a new concept termed 'switch-peptides' which allows the controlled onset of polypeptide folding and misfolding in vitro and in vivo, starting from a soluble, non-toxic precursor molecule. As a major feature, the folding process is initiated by enzyme-triggered N,O-acyl migrations restoring the native peptide backbone in situ. As the folding is set off in the moment of creating the bioactive molecule ('in statu nascendi', ISN), our concept allows for the first time the investigation of the early steps of protein misfolding as relevant in degenerative diseases, opening new perspectives for the rational design of therapeutically relevant compounds.

The application of Fick's law to evaluate the period of stay of mega-olivines in alkaline lavas

The integration of the differential equation of the second law of Fick applied to the diffusion of chemical elements in a semi-infinite solid made it easier to estimate the time of stay of olivine mega-cristals in contact with the host lava The results of this research show the existence of two groups of olivine. The first remained in contact with the magmatic liquid during 19 to 22 days, while the second remained so during only 5 to 9 days. This distinction is correlative to that based on the qualitative observation.

The INTERMED questionnaire for predicting return to work after a multidisciplinary rehabilitation program for chronic low back pain.

OBJECTIVES: To evaluate the performance of the INTERMED questionnaire score, alone or combined with other criteria, in predicting return to work after a multidisciplinary rehabilitation program in patients with non-specific chronic low back pain. METHODS: The INTERMED questionnaire is a biopsychosocial assessment and clinical classification tool that separates heterogeneous populations into subgroups according to case complexity. We studied 88 patients with chronic low back pain who followed an intensive multidisciplinary rehabilitation program on an outpatient basis. Before the program, we recorded the INTERMED score, radiological abnormalities, subjective pain severity, and sick leave duration. Associations between these variables and return to full-time work within 3 months after the end of the program were evaluated using one-sided Fisher tests and univariate logistic regression followed by multivariate logistic regression. RESULTS: The univariate analysis showed a significant association between the INTERMED score and return to work (P<0.001; odds ratio, 0.90; 95% confidence interval, 0.86-0.96). In the multivariate analysis, prediction was best when the INTERMED score and sick leave duration were used in combination (P=0.03; odds ratio, 0.48; 95% confidence interval, 0.25-0.93). CONCLUSION: The INTERMED questionnaire is useful for evaluating patients with chronic low back pain. It could be used to improve the selection of patients for intensive multidisciplinary programs, thereby improving the quality of care, while reducing healthcare costs.

Developing a theoretical framework using a nursing perspective to investigate perceived health in the "Sandwich Generation" group

Coexisting workloads from professional, household and family, and caregiving activities for frail parents expose middle-aged individuals, the so-called "Sandwich Generation", to potential health risks. Current trends suggest that this situation will continue or increase. Thus SG health promotion has become a nursing concern. Most existing research considers coexisting workloads a priori pathogenic. Most studies have examined the association of one, versus two, of these three activities with health. Few studies have used a nursing perspective. This article presents the development of a framework based on a nursing model. We integrated Siegrist's Effort-Reward Imbalance middle-range theory into "Neuman Systems Model". The latter was chosen for its salutogenic orientation, its attention to preventive nursing interventions and the opportunity it provides to simultaneously consider positive and negative perceptions of SG health and SG coexisting workloads. Finally, it facilitated a theoretical identification of health protective factors.

Social contexts of sports-practicing youths' hazardous drinking.

Sports-practicing youths are at an elevated risk for alcohol use and misuse. Although much attention has recently been given to depicting subgroups facing the greatest threats, little evidence exists on the contexts in which their drinking takes place. Using data from a cross-sectional study on youth sports participation and substance use in the French-speaking part of Switzerland, this study focused on the social contexts associated with hazardous drinking of 894 sports-practicing adolescents aged 16 to 20. Divided between those who had been drunk in the last month (hazardous drinkers, n = 315) and those who had not (n = 579), sports-practicing adolescents were compared on reported gatherings (sports-related, sports-unrelated, mixed) likely linked to their drinking behaviour. Mixed social contexts, followed by sports-unrelated ones, were reported as the most common context by both male and female youths who practiced sports. After controlling for several possible confounders, male hazardous drinkers were more than 3 times more likely to report sports-unrelated social contexts as the most common, compared to sport-related ones, while females were more than 7 times more likely to do so. Our findings seem to indicate that, rather than focusing only on sports-related factors, prevention of alcohol misuse among sports-practicing youths should also pay attention to the social contextualisation of their hazardous drinking.

Neuroscience, quantum indeterminism and the Cartesian soul.

Quantum indeterminism is frequently invoked as a solution to the problem of how a disembodied soul might interact with the brain (as Descartes proposed), and is sometimes invoked in theories of libertarian free will even when they do not involve dualistic assumptions. Taking as example the Eccles-Beck model of interaction between self (or soul) and brain at the level of synaptic exocytosis, I here evaluate the plausibility of these approaches. I conclude that Heisenbergian uncertainty is too small to affect synaptic function, and that amplification by chaos or by other means does not provide a solution to this problem. Furthermore, even if Heisenbergian effects did modify brain functioning, the changes would be swamped by those due to thermal noise. Cells and neural circuits have powerful noise-resistance mechanisms, that are adequate protection against thermal noise and must therefore be more than sufficient to buffer against Heisenbergian effects. Other forms of quantum indeterminism must be considered, because these can be much greater than Heisenbergian uncertainty, but these have not so far been shown to play a role in the brain.

Anti-tumor necrosis factor drug survival in axial spondyloarthritis is independent of the classification criteria.

To compare the impact of meeting specific classification criteria [modified New York (mNY), European Spondyloarthropathy Study Group (ESSG), and Assessment of SpondyloArthritis international Society (ASAS) criteria] on anti-tumor necrosis factor (anti-TNF) drug retention, and to determine predictive factors of better drug survival. All patients fulfilling the ESSG criteria for axial spondyloarthritis (SpA) with available data on the axial ASAS and mNY criteria, and who had received at least one anti-TNF treatment were retrospectively retrieved in a single academic institution in Switzerland. Drug retention was computed using survival analysis (Kaplan-Meier), adjusted for potential confounders. Of the 137 patients classified as having axial SpA using the ESSG criteria, 112 also met the ASAS axial SpA criteria, and 77 fulfilled the mNY criteria. Drug retention rates at 12 and 24 months for the first biologic therapy were not significantly different between the diagnostic groups. Only the small ASAS non-classified axial SpA group (25 patients) showed a nonsignificant trend toward shorter drug survival. Elevated CRP level, but not the presence of bone marrow edema on magnetic resonance imaging (MRI) scans, was associated with significantly better drug retention (OR 7.9, ICR 4-14). In this cohort, anti-TNF drug survival was independent of the classification criteria. Elevated CRP level, but not positive MRI, was associated with better drug retention.

The pollutant diethylhexyl phthalate regulates hepatic energy metabolism via species-specific PPARalpha-dependent mechanisms.

Background: The modulation of energetic homeostasis by pollutants has recently emerged as a potential contributor to the onset of metabolic disorders. Diethylhexyl phthalate (DEHP) is a widely used industrial plasticizer to which humans are widely exposed. Phthalates can activate the three peroxisome proliferatoractivated receptor (PPAR) isotypes on cellular models and induce peroxisome proliferation in rodents.Objectives: In this study, we aimed to evaluate the systemic and metabolic consequences of DEHP exposure that have remained so far unexplored and to characterize the underlying molecular mechanisms of action.Methods: As a proof of concept and mechanism, genetically engineered mouse models of PPARs were exposed to high doses of DEHP, followed by metabolic and molecular analyses.Results: DEHP-treated mice were protected from diet-induced obesity via PPARalpha-dependent activation of hepatic fatty acid catabolism, whereas the activity of neither PPARbeta nor PPARgamma was affected. However, the lean phenotype observed in response to DEHP in wild-type mice was surprisingly abolished in PPARalpha-humanized mice. These species differences are associated with a different pattern of coregulator recruitment.Conclusion: These results demonstrate that DEHP exerts species-specific metabolic actions that rely to a large extent on PPARalpha signaling and highlight the metabolic importance of the species-specific activation of PPARalpha by xenobiotic compounds. Editor's SummaryDiethylhexyl phthalate (DEHP) is an industrial plasticizer used in cosmetics, medical devices, food packaging, and other applications. Evidence that DEHP metabolites can activate peroxisome proliferatoractivated receptors (PPARs) involved in fatty acid oxidation (PPARalpha and PPARbeta) and adiposite function and insulin resistance (PPARgamma) has raised concerns about potential effects of DEHP on metabolic homeostasis. In rodents, PPARalpha activation also induces hepatic peroxisome proliferation, but this response to PPARalpha activation is not observed in humans. Feige et al. (p. 234) evaluated systemic and metabolic consequences of high-dose oral DEHP in combination with a high-fat diet in wild-type mice and genetically engineered mouse PPAR models. The authors report that mice exposed to DEHP gained less weight than controls, without modifying their feeding behavior; they also exhibited lower triglyceride levels, smaller adipocytes, and improved glucose tolerance compared with controls. These effects, which were observed in mice fed both high-fat and standard diets, appeared to be mediated by PPARalpha-dependent activation of hepatic fatty acid catabolism without apparent involvement of PPARbeta or PPARgamma. However, mouse models that expressed human (versus mouse) PPARalpha tended to gain more weight on a high-fat diet than their DHEP-unexposed counterparts. The authors conclude that findings support species-specific metabolic effects of DEHP mediated by PPARalpha activation.

Self-identity and religion/spirituality

Although medicine is practised in a secular setting, religious and spiritual issues have an impact on patient perspectives regarding their health and the management of any disorders that may afflict them. This is especially true in psychiatry, as feelings of spirituality and religiousness are very prevalent among the mentally ill. Clinicians are rarely aware of the importance of religion and understand little of its value as a mediating force for coping with mental illness. This book addresses various issues concerning mental illness in psychiatry: the relation of religious issues to mental health; the tension between a theoretical approach to problems and psychiatric approaches; the importance of addressing these varying approaches in patient care and how to do so; and differing ways to approach Christian, Muslim, and Buddhist patients. This is the first book to specifically cover the impact of religion and spirituality on mental illness.

Hard-wired heterogeneity in blood stem cells revealed using a dynamic regulatory network model.

MOTIVATION: Combinatorial interactions of transcription factors with cis-regulatory elements control the dynamic progression through successive cellular states and thus underpin all metazoan development. The construction of network models of cis-regulatory elements, therefore, has the potential to generate fundamental insights into cellular fate and differentiation. Haematopoiesis has long served as a model system to study mammalian differentiation, yet modelling based on experimentally informed cis-regulatory interactions has so far been restricted to pairs of interacting factors. Here, we have generated a Boolean network model based on detailed cis-regulatory functional data connecting 11 haematopoietic stem/progenitor cell (HSPC) regulator genes. RESULTS: Despite its apparent simplicity, the model exhibits surprisingly complex behaviour that we charted using strongly connected components and shortest-path analysis in its Boolean state space. This analysis of our model predicts that HSPCs display heterogeneous expression patterns and possess many intermediate states that can act as 'stepping stones' for the HSPC to achieve a final differentiated state. Importantly, an external perturbation or 'trigger' is required to exit the stem cell state, with distinct triggers characterizing maturation into the various different lineages. By focusing on intermediate states occurring during erythrocyte differentiation, from our model we predicted a novel negative regulation of Fli1 by Gata1, which we confirmed experimentally thus validating our model. In conclusion, we demonstrate that an advanced mammalian regulatory network model based on experimentally validated cis-regulatory interactions has allowed us to make novel, experimentally testable hypotheses about transcriptional mechanisms that control differentiation of mammalian stem cells. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Religion/Spirituality and dissociative disorders

Although medicine is practised in a secular setting, religious and spiritual issues have an impact on patient perspectives regarding their health and the management of any disorders that may afflict them. This is especially true in psychiatry, as feelings of spirituality and religiousness are very prevalent among the mentally ill. Clinicians are rarely aware of the importance of religion and understand little of its value as a mediating force for coping with mental illness. This book addresses various issues concerning mental illness in psychiatry: the relation of religious issues to mental health; the tension between a theoretical approach to problems and psychiatric approaches; the importance of addressing these varying approaches in patient care and how to do so; and differing ways to approach Christian, Muslim, and Buddhist patients. This is the first book to specifically cover the impact of religion and spirituality on mental illness.

Decoding sequence learning from single-trial intracranial EEG in humans.

We propose and validate a multivariate classification algorithm for characterizing changes in human intracranial electroencephalographic data (iEEG) after learning motor sequences. The algorithm is based on a Hidden Markov Model (HMM) that captures spatio-temporal properties of the iEEG at the level of single trials. Continuous intracranial iEEG was acquired during two sessions (one before and one after a night of sleep) in two patients with depth electrodes implanted in several brain areas. They performed a visuomotor sequence (serial reaction time task, SRTT) using the fingers of their non-dominant hand. Our results show that the decoding algorithm correctly classified single iEEG trials from the trained sequence as belonging to either the initial training phase (day 1, before sleep) or a later consolidated phase (day 2, after sleep), whereas it failed to do so for trials belonging to a control condition (pseudo-random sequence). Accurate single-trial classification was achieved by taking advantage of the distributed pattern of neural activity. However, across all the contacts the hippocampus contributed most significantly to the classification accuracy for both patients, and one fronto-striatal contact for one patient. Together, these human intracranial findings demonstrate that a multivariate decoding approach can detect learning-related changes at the level of single-trial iEEG. Because it allows an unbiased identification of brain sites contributing to a behavioral effect (or experimental condition) at the level of single subject, this approach could be usefully applied to assess the neural correlates of other complex cognitive functions in patients implanted with multiple electrodes.