The microtubule plus-end localization of Aspergillus dynein is important for dynein-early-endosome interaction but not for dynein ATPase activation

Cytoplasmic dynein in filamentous fungi accumulates at microtubule plus-ends near the hyphal tip, which is important for minus-end-directed transport of early endosomes. It was hypothesized that dynein is switched on at the plus-end by cargo association. Here, we show in Aspergillus nidulans that kinesin-1-dependent plus-end localization is not a prerequisite for dynein ATPase activation. First, the Walker A and Walker B mutations in the dynein heavy chain AAA1 domain implicated in blocking different steps of the ATPase cycle cause different effects on dynein localization to microtubules, arguing against the suggestion that ATPase is inactive before arriving at the plus-end. Second, dynein from kinA (kinesin 1) mutant cells has normal ATPase activity despite the absence of dynein plus-end accumulation. In kinA hyphae, dynein localizes along microtubules and does not colocalize with abnormally accumulated early endosomes at the hyphal tip. This is in contrast to the colocalization of dynein and early endosomes in the absence of NUDF/LIS1. However, the Walker B mutation allows dynein to colocalize with the hyphal-tip-accumulated early endosomes in the kinA background. We suggest that the normal ability of dyenin to interact with microtubules as an active minus-end-directed motor demands kinesin-1-mediated plus-end accumulation for effective interactions with early endosomes.

Pulse-front tilt for short-wavelength lasing by means of traveling-wave plasma-excitation

Generation of coherent short-wavelength radiation across a plasma column is dramatically improved under traveling-wave excitation (TWE). The latter is optimized when its propagation is close to the speed of light, which implies small-angle target-irradiation. Yet, short-wavelength lasing needs large irradiation angles in order to increase the optical penetration of the pump into the plasma core. Pulse-front back-tilt is considered to overcome such trade-off. In fact, the TWE speed depends on the pulse-front slope (envelope of amplitude), whereas the optical penetration depth depends on the wave-front slope (envelope of phase). Pulse-front tilt by means of compressor misalignment was found effective only if coupled with a high-magnification front-end imaging/focusing component. It is concluded that speed matching should be accomplished with minimal compressor misalignment and maximal imaging magnification.

SMARTDIAB: a communication and information technology approach for the intelligent monitoring, management and follow-up of type 1 diabetes patients

SMARTDIAB is a platform designed to support the monitoring, management, and treatment of patients with type 1 diabetes mellitus (T1DM), by combining state-of-the-art approaches in the fields of database (DB) technologies, communications, simulation algorithms, and data mining. SMARTDIAB consists mainly of two units: 1) the patient unit (PU); and 2) the patient management unit (PMU), which communicate with each other for data exchange. The PMU can be accessed by the PU through the internet using devices, such as PCs/laptops with direct internet access or mobile phones via a Wi-Fi/General Packet Radio Service access network. The PU consists of an insulin pump for subcutaneous insulin infusion to the patient and a continuous glucose measurement system. The aforementioned devices running a user-friendly application gather patient's related information and transmit it to the PMU. The PMU consists of a diabetes data management system (DDMS), a decision support system (DSS) that provides risk assessment for long-term diabetes complications, and an insulin infusion advisory system (IIAS), which reside on a Web server. The DDMS can be accessed from both medical personnel and patients, with appropriate security access rights and front-end interfaces. The DDMS, apart from being used for data storage/retrieval, provides also advanced tools for the intelligent processing of the patient's data, supporting the physician in decision making, regarding the patient's treatment. The IIAS is used to close the loop between the insulin pump and the continuous glucose monitoring system, by providing the pump with the appropriate insulin infusion rate in order to keep the patient's glucose levels within predefined limits. The pilot version of the SMARTDIAB has already been implemented, while the platform's evaluation in clinical environment is being in progress.

Fourier optics study of traveling-wave excitation at short- wavelength plasma-lasing

Traveling-wave excitation close to the speed of light implies small-angle target-irradiation. Yet, short-wavelength lasing needs large irradiation angles. Pulse-front back-tilt is considered to overcome such trade-off. Pulse-front tilt by means of compressor misalignment was found effective only if coupled with a strong front-end imaging/focusing component.

A Baseline Wander Tracking System for Artifact Rejection in Long-Term Electrocardiography

Long-term electrocardiogram (ECG) signals might suffer from relevant baseline disturbances during physical activity. Motion artifacts in particular are more pronounced with dry surface or esophageal electrodes which are dedicated to prolonged ECG recording. In this paper we present a method called baseline wander tracking (BWT) that tracks and rejects strong baseline disturbances and avoids concurrent saturation of the analog front-end. The proposed algorithm shifts the baseline level of the ECG signal to the middle of the dynamic input range. Due to the fast offset shifts, that produce much steeper signal portions than the normal ECG waves, the true ECG signal can be reconstructed offline and filtered using computationally intensive algorithms. Based on Monte Carlo simulations we observed reconstruction errors mainly caused by the non-linearity inaccuracies of the DAC. However, the signal to error ratio of the BWT is higher compared to an analog front-end featuring a dynamic input ranges above 15 mV if a synthetic ECG signal was used. The BWT is additionally able to suppress (electrode) offset potentials without introducing long transients. Due to its structural simplicity, memory efficiency and the DC coupling capability, the BWT is dedicated to high integration required in long-term and low-power ECG recording systems.

Metabolomics in plant-herbivore interactions: challenges and applications

Metabolomics as the study of the entire set of metabolites of a given organism is an important frontier in life sciences. As a tool that captures the ‘front end’ of cellular machineries, metabolomics is particularly suited to investigate biotic interactions, including for instance the interplay between plants and insects. In this review, we discuss the opportunities and challenges of metabolomics to study plant–herbivore interactions. We first present a brief overview of the typical analytical workflows used in metabolomics and their associated issues, in particular those related to metabolome coverage and compound identification. Second, recent advances in the field of plant–herbivore relationships that are promoted by non-targeted approaches are reviewed, with examples ranging from classical herbivore resistance patterns to plant-mediated interactions across different spatial scales and volatile-mediated tritrophic interactions. Through general considerations and the discussion of a few selected case studies, our review highlights the potential and challenges of metabolomics as a research approach to understand biological interfaces.

Antagonistic effects of ondansetron and tramadol? A randomized placebo and active drug controlled study

Opposing effects of ondansetron and tramadol on the serotonin pathway have been suggested which possibly increase tramadol consumption and emesis when co-administered. In a randomized, double-blinded study, 179 patients received intravenous ondansetron, metoclopramide, or placebo for emesis prophylaxis. Analgesic regimen consisted of tramadol intraoperative loading and subsequent patient-controlled analgesia. Tramadol consumption and response to antiemetic treatment were compared. Additionally, plasma concentrations of ondansetron and (+)O-demethyltramadol and CYP2D6 genetic variants were analyzed as possible confounders influencing analgesic and antiemetic efficacy. Tramadol consumption did not differ between the groups. Response rate to antiemetic prophylaxis was superior in patients receiving ondansetron (85.0%) compared with placebo (66.7%, P = .046), with no difference to metoclopramide (69.5%). Less vomiting was reported in the immediate postoperative hours in the verum groups (ondansetron 5.0%, metoclopramide 5.1%) compared with placebo (18.6%; P = .01). Whereas plasma concentrations of (+)O-demethyltramadol were significantly correlated to CYP2D6 genotype, no influence was detected for ondansetron. Co-administration of ondansetron neither increased tramadol consumption nor frequency of PONV in this postoperative setting. PERSPECTIVE: Controversial findings were reported for efficacy of tramadol and ondansetron when co-administered due to their opposing serotonergic effects. Co-medication of these drugs neither increased postoperative analgesic consumption nor frequency of emesis in this study enrolling patients recovering from major surgery.

Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial

Eosinophilic oesophagitis (EoO) is a clinicopathological condition defined by proton pump inhibitor-refractory oesophageal symptoms combined with oesophageal eosinophilia. The pharmacodynamic effect of mepolizumab (a humanised anti-interleukin-5 monoclonal antibody) in EoO was evaluated.

Efficacy and safety of the Betamethasone valerate 0.1% plaster in mild-to-moderate chronic plaque psoriasis: a randomized, parallel-group, active-controlled, phase III study

Corticosteroids are a versatile option for the treatment of mild-to-moderate psoriasis due to their availability in a wide range of potencies and formulations. Occlusion of the corticosteroid is a widely accepted procedure to enhance the penetration of the medication, thereby improving its effectiveness. Betamethasone valerate (BMV) is a moderately potent corticosteroid that is available as a cream, ointment, and lotion. A ready-to-use occlusive dressing, which provides a continuous sustained release of BMV, has been developed for the treatment of psoriasis.

Perioperative use of crystalloids in patients undergoing open radical cystectomy: balanced Ringer's maleate versus a glucose 5%/potassium-based balanced solution: study protocol for a randomized controlled trial

BACKGROUND The optimal crystalloid solution to use perioperatively in patients undergoing open radical cystectomy remains unclear. Many of the fluids used for intravenous hydration contain supraphysiologic concentrations of chloride, which can induce hyperchloremia and metabolic acidosis, resulting in renal vasoconstriction and decreased renal function. In addition, patients receiving less fluid and less sodium show faster recovery of gastrointestinal (GI) function after colonic surgery. METHODS AND DESIGN This is an investigator-initiated, single-center, randomized, controlled, parallel group trial with assessor-blinded outcome assessment, in the Department of Urology, University Hospital Bern, Switzerland. The study will involve 44 patients with bladder cancer scheduled for radical cystectomy and urinary diversion. The primary outcome is the duration between the end of surgery and the return of the GI function (first defecation). Secondary outcomes are fluid balance (body weight difference postoperatively versus preoperatively) and the incidence of kidney function disorders according to the Risk-Injury-Failure-Loss-End Stage Renal Disease (RIFLE classification). An equal number of patients are allocated to receive Ringerfundin® solution or a glucose/potassium-based balanced crystalloid solution as baseline infusion during the entire time that intravenous administration of fluid is necessary during the perioperative period. The randomized crystalloid solution is infused at a rate of 1 ml/kg/h until the bladder has been removed, followed by 3 ml/kg/h until the end of surgery. Postoperative hydration is identical in both groups and consists of 1,500 ml of the randomized crystalloid solution per 24 hours. Postoperative patient care is identical in both groups; patients are allowed to drink clear fluids immediately after surgery, and liquid diet is started on postoperative day 1, as well as active mobilization and the use of chewing gum. Body weight is measured daily in the morning. Time of first flatus and first defecation are recorded. DISCUSSION This trial assesses the benefits and harms of two different balanced crystalloid solutions for perioperative fluid management in patients undergoing open radical cystectomy with urinary diversion, with regard to return of GI function and effects on postoperative renal function. TRIAL REGISTRATION Current Controlled Trials ISRCTN32976792 (registered on November 21 2013).

Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by dense tissue eosinophilia; it is refractory to proton pump inhibitor therapy. EoE affects all age groups but most frequently individuals between 20 and 50 years of age. Topical corticosteroids are effective in pediatric patients with EoE, but no controlled studies of corticosteroids have been reported in adult patients.

Effectiveness of individual resource-oriented joint protection education in people with rheumatoid arthritis. A randomized controlled trial

the modern joint protection (JP) concept for people with rheumatoid arthritis (RA) is an active coping strategy to improve daily tasks and role performance by changing working methods and using assistive devices. Effective group JP education includes psycho-educational interventions. The Pictorial Representation of Illness and Self Measure (PRISM) is an interactive hands-on-tool, assessing (a) the individual's perceived burden of illness and (b) relevant individual resources. Both issues are important for intrinsic motivation to take action and change behaviour. This study compared individual conventional JP education (C-JP) with PRISM-based JP education (PRISM-JP).