Irrigation of continent catheterizable ileal pouches: tap water can replace sterile solutions because it is safe, easy, and economical

Continent catheterizable ileal pouches require regular irrigations to reduce the risk of bacteriuria and urinary tract infections (UTIs).

Regulatory mechanism of the light-activable allosteric switch LOV-TAP for the control of DNA binding: a computer simulation study

The spatio-temporal control of gene expression is fundamental to elucidate cell proliferation and deregulation phenomena in living systems. Novel approaches based on light-sensitive multiprotein complexes have recently been devised, showing promising perspectives for the noninvasive and reversible modulation of the DNA-transcriptional activity in vivo. This has lately been demonstrated in a striking way through the generation of the artificial protein construct light-oxygen-voltage (LOV)-tryptophan-activated protein (TAP), in which the LOV-2-Jα photoswitch of phototropin1 from Avena sativa (AsLOV2-Jα) has been ligated to the tryptophan-repressor (TrpR) protein from Escherichia coli. Although tremendous progress has been achieved on the generation of such protein constructs, a detailed understanding of their functioning as opto-genetical tools is still in its infancy. Here, we elucidate the early stages of the light-induced regulatory mechanism of LOV-TAP at the molecular level, using the noninvasive molecular dynamics simulation technique. More specifically, we find that Cys450-FMN-adduct formation in the AsLOV2-Jα-binding pocket after photoexcitation induces the cleavage of the peripheral Jα-helix from the LOV core, causing a change of its polarity and electrostatic attraction of the photoswitch onto the DNA surface. This goes along with the flexibilization through unfolding of a hairpin-like helix-loop-helix region interlinking the AsLOV2-Jα- and TrpR-domains, ultimately enabling the condensation of LOV-TAP onto the DNA surface. By contrast, in the dark state the AsLOV2-Jα photoswitch remains inactive and exerts a repulsive electrostatic force on the DNA surface. This leads to a distortion of the hairpin region, which finally relieves its tension by causing the disruption of LOV-TAP from the DNA.

TAP deficiency syndrome: chronic rhinosinusitis and conductive hearing loss

Nose-ear-throat manifestations of immunodeficiency disorders represent a diagnostic challenge for clinicians as these diseases often constitute the initial sign for connective disorders or autoimmune disease. The history of chronic rhinosinusitis and conductive hearing loss is often non specific. Therefore attention to an HLA class I deficiency must be considered if the disease has not been diagnosed on routine examination. One of the syndromes is due to a defective TAP complex, the peptide transporter complex associated with antigen presentation. Herein, we report two sisters with TAP-deficiency. The treatment of choice for TAP-deficient patients is conservative.

Ventricular enlargement due to acute hypernatremia in a patient with a ventriculoperitoneal shunt

Patients requiring CSF shunts frequently have comorbidities that can influence water and electrolyte balances. The authors report on a case involving a ventriculoperitoneal shunt in a patient who underwent intravenous hyperhydration and withdrawal of vasopressin substitution prior to scheduled high-dose chemotherapy regimen for a metastatic suprasellar germinoma. After acute neurological deterioration, the patient underwent CT scanning that demonstrated ventriculomegaly. A shunt tap revealed no flow and negative opening pressure. Due to suspicion of proximal shunt malfunction, the comatose patient underwent immediate surgical exploration of the ventricle catheter, which was found to be patent. However, acute severe hypernatremia was diagnosed during the procedure. After correction of the electrolyte disturbances, the patient regained consciousness and made a good recovery. Although rare, the effects of acute severe hypernatremia on brain volume and ventricular size should be considered in the differential diagnosis of ventriculoperitoneal shunt failure.

Knowledge Management and Decision Support for Sustainable Land Management

Much research has focused on desertification and land degradation assessments without putting sufficient emphasis on prevention and mitigation, although the concept of sustainable land management (SLM) is increasingly being acknowledged. A variety of SLM measures have already been applied at the local level, but they are rarely adequately recognised, evaluated, shared or used for decision support. WOCAT (World Overview of Technologies and Approaches) has developed an internationally recognised, standardised methodology to document and evaluate SLM technologies and approaches, including spatial distribution, allowing the sharing of SLM knowledge worldwide. The recent methodological integration into a participatory process allows now analysing and using this knowledge for decision support at the local and national level. The use of the WOCAT tools stimulates evaluation (self-evaluation as well as learning from comparing experiences) within SLM initiatives where all too often there is not only insufficient monitoring but also a lack of critical analysis. The comprehensive questionnaires and database system facilitate to document, evaluate and disseminate local experiences of SLM technologies and their implementation approaches. This evaluation process - in a team of experts and together with land users - greatly enhances understanding of the reasons behind successful (or failed) local practices. It has now been integrated into a new methodology for appraising and selecting SLM options. The methodology combines a local collective learning and decision approach with the use of the evaluated global best practices from WOCAT in a concise three step process: i) identifying land degradation and locally applied solutions in a stakeholder learning workshop; ii) assessing local solutions with the standardised WOCAT tool; iii) jointly selecting promising strategies for implementation with the help of a decision support tool. The methodology has been implemented in various countries and study sites around the world mainly within the FAO LADA (Land Degradation Assessment Project) and the EU-funded DESIRE project. Investments in SLM must be carefully assessed and planned on the basis of properly documented experiences and evaluated impacts and benefits: concerted efforts are needed and sufficient resources must be mobilised to tap the wealth of knowledge and learn from SLM successes.

Suppression of transforming growth factor beta signalling aborts caerulein induced pancreatitis and eliminates restricted stimulation at high caerulein concentrations

BACKGROUND: Transforming growth factors betas (TGF-betas) are implicated in pancreatic tissue repair but their role in acute pancreatitis is not known. To determine whether endogenous TGF-betas modulate the course of caerulein induced acute pancreatitis, caerulein was administered to wild-type (FVB-/-) and transgenic mice that are heterozygous (FVB+/-) for expression of a dominant negative type II TGF-beta receptor. METHODS: After 7 hourly supramaximal injections of caerulein, the pancreas was evaluated histologically and serum was assayed for amylase and lipase levels. Next, the effects of caerulein on amylase secretion were determined in mouse pancreatic acini, and cholecystokinin (CCK) receptor expression was assessed. RESULTS: The normal mouse pancreas was devoid of inflammatory cells whereas the pancreas from transgenic mice contained lymphocytic infiltrates. Caerulein injection in wild-type mice resulted in 6- and 36-fold increases in serum amylase and lipase levels, respectively, increased serum trypsinogen activation peptide (TAP) levels, gross oedema and a marked inflammatory response in the pancreas that consisted mainly of neutrophils and macrophages. By contrast, FVB+/- mice exhibited minimal alterations in response to caerulein with attenuated neutrophil-macrophage infiltrates. Moreover, acini from FVB+/- mice did not exhibit restricted stimulation at high caerulein concentrations, even though CCK receptor mRNA levels were not decreased. CONCLUSION: Our findings indicate that a functional TGF-beta signalling pathway may be required for caerulein to induce acute pancreatitis and for the CCK receptor to induce acinar cell damage at high ligand concentrations. Our results also support the concept that restricted stimulation at high caerulein concentrations contributes to the ability of caerulein to induce acute pancreatitis.

Evaluation of magnetic resonance colonography at 3.0 Tesla regarding diagnostic accuracy and image quality

OBJECTIVES: To assess magnetic resonance (MR)-colonography (MRC) for detection of colorectal lesions using two different T1w three-dimensional (3D)-gradient-recalled echo (GRE)-sequences and integrated parallel data acquisition (iPAT) at a 3.0 Tesla MR-unit. MATERIALS AND METHODS: In this prospective study, 34 symptomatic patients underwent dark lumen MRC at a 3.0 Tesla unit before conventional colonoscopy (CC). After colon distension with tap water, 2 high-resolution T1w 3D-GRE [3-dimensional fast low angle shot (3D-FLASH), iPAT factor 2 and 3D-volumetric interpolated breathhold examination (VIBE), iPAT 3] sequences were acquired without and after bolus injection of gadolinium. Prospective evaluation of MRC was performed. Image quality of the different sequences was assessed qualitatively and quantitatively. The findings of the same day CC served as standard of reference. RESULTS: MRC identified all polyps >5 mm (16 of 16) in size and all carcinomas (4 of 4) correctly. Fifty percent of the small polyps 0.6). CONCLUSIONS: MRC using 3D-GRE-sequences and iPAT is feasible at 3.0 T-systems. The high-resolution 3D-FLASH was slightly preferred over the 3D-VIBE because of better image quality, although both used sequences showed no statistical significant difference.

Cognitive functioning, behavior, and quality of life after stroke in childhood

Rationale: To provide a better understanding of cognitive functioning, motor outcome, behavior and quality of life after childhood stroke and to study the relationship between variables expected to influence rehabilitation and outcome (age at stroke, time elapsed since stroke, lateralization, location and size of lesion). Methods: Children who suffered from stroke between birth and their eighteenth year of life underwent an assessment consisting of cognitive tests (WISC-III, WAIS-R, K-ABC, TAP, Rey-Figure, German Version of the CVLT) and questionnaires (Conner's Scales, KIDSCREEN). Results: Twenty-one patients after stroke in childhood (15 males, mean 11;11 years, SD 4;3, range 6;10-21;2) participated in the study. Mean Intelligence Quotients (IQ) were situated within the normal range (mean Full Scale IQ 96.5, range IQ 79-129). However, significantly more patients showed deficits in various cognitive domains than expected from a healthy population (Performance IQ p = .000; Digit Span p = .000, Arithmetic's p = .007, Divided Attention p = .028, Alertness p = .002). Verbal IQ was significantly better than Performance IQ in 13 of 17 patients, independent of the hemispheric side of lesion. Symptoms of ADHD occurred more often in the patients' sample than in a healthy population (learning difficulties/inattention p = .000; impulsivity/hyperactivity p = .006; psychosomatics p = .006). Certain aspects of quality of life were reduced (autonomy p = .003; parents' relation p = .003; social acceptance p = .037). Three patients had a right-sided hemiparesis, mean values of motor functions of the other patients were slightly impaired (sequential finger movements p = .000, hand alternation p = .001, foot tapping p = .043). In patients without hemiparesis, there was no relation between the lateralization of lesion and motor outcome. Lesion that occurred in the midst of childhood (5-10 years) led to better cognitive outcome than lesion in the very early (0-5 years) or late childhood (10-18 years). Other variables such as presence of seizure, elapsed time since stroke and size of lesion had a small to no impact on prognosis. Conclusion: Moderate cognitive and motor deficits, behavioral problems, and impairment in some aspects of quality of life frequently remain after stroke in childhood. Visuospatial functions are more often reduced than verbal functions, independent of the hemispheric side of lesion. This indicates a functional superiority of verbal skills compared to visuospatial skills in the process of recovery after brain injury. Compared to the cognitive outcome following stroke in adults, cognitive sequelae after childhood stroke do indicate neither the lateralization nor the location of the lesion focus. Age at stroke seems to be the only determining factor influencing cognitive outcome.

Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA export

Export of mRNA from the nucleus is linked to proper processing and packaging into ribonucleoprotein complexes. Although several observations indicate a coupling between mRNA 3' end formation and export, it is not known how these two processes are mechanistically connected. Here, we show that a subunit of the mammalian pre-mRNA 3' end processing complex, CF I(m)68, stimulates mRNA export. CF I(m)68 shuttles between the nucleus and the cytoplasm in a transcription-dependent manner and interacts with the mRNA export receptor NXF1/TAP. Consistent with the idea that CF I(m)68 may act as a novel adaptor for NXF1/TAP, we show that CF I(m)68 promotes the export of a reporter mRNA as well as of endogenous mRNAs, whereas silencing by RNAi results in the accumulation of mRNAs in the nucleus. Moreover, CF I(m)68 associates with 80S ribosomes but not polysomes, suggesting that it is part of the mRNP that is remodeled in the cytoplasm during the initial stages of translation. These results reveal a novel function for the pre-mRNA 3' end processing factor CF I(m)68 in mRNA export.

Promoting research-user collaboration: an assessment of funding schemes: Fifth NCCR North-South Report on Effectiveness

Donors increasingly require that the research they fund be of benefit for society and the environment. To this end, researchers addressing complex and uncertain problems should work together with research users. This is not always easy: researchers are expected to collaborate with non-academic partners, but are not funded for the additional work. Collaborative research projects often cannot tap the full potential of user engagement. Therefore, specific institutional and organisational conditions are necessary that foresee or even foster research–user engagement; funding schemes are one possible solution. Right from the start, the NCCR North-South programme introduced Partnership Actions for Mitigating Syndromes of Global Change (PAMS). This evaluation assesses the types of collaboration supported by PAMS, as well as the value of PAMS as a funding scheme for collaboration. It compares PAMS with similar funding schemes of other universities, research programmes, or projects, and contains recommendations.

Sonic intelligence as a virtual therapeutic environment

This paper reports on the results of a research project, on comparing one virtual collaborative environment with a first-person visual immersion (first-perspective interaction) and a second one where the user interacts through a sound-kinetic virtual representation of himself (avatar), as a stress-coping environment in real-life situations. Recent developments in coping research are proposing a shift from a trait-oriented approach of coping to a more situation-specific treatment. We defined as real-life situation a target-oriented situation that demands a complex coping skills inventory of high self-efficacy and internal or external "locus of control" strategies. The participants were 90 normal adults with healthy or impaired coping skills, 25-40 years of age, randomly spread across two groups. There was the same number of participants across groups and gender balance within groups. All two groups went through two phases. In Phase I, Solo, one participant was assessed using a three-stage assessment inspired by the transactional stress theory of Lazarus and the stress inoculation theory of Meichenbaum. In Phase I, each participant was given a coping skills measurement within the time course of various hypothetical stressful encounters performed in two different conditions and a control group. In Condition A, the participant was given a virtual stress assessment scenario relative to a first-person perspective (VRFP). In Condition B, the participant was given a virtual stress assessment scenario relative to a behaviorally realistic motion controlled avatar with sonic feedback (VRSA). In Condition C, the No Treatment Condition (NTC), the participant received just an interview. In Phase II, all three groups were mixed and exercised the same tasks but with two participants in pairs. The results showed that the VRSA group performed notably better in terms of cognitive appraisals, emotions and attributions than the other two groups in Phase I (VRSA, 92%; VRFP, 85%; NTC, 34%). In Phase II, the difference again favored the VRSA group against the other two. These results indicate that a virtual collaborative environment seems to be a consistent coping environment, tapping two classes of stress: (a) aversive or ambiguous situations, and (b) loss or failure situations in relation to the stress inoculation theory. In terms of coping behaviors, a distinction is made between self-directed and environment-directed strategies. A great advantage of the virtual collaborative environment with the behaviorally enhanced sound-kinetic avatar is the consideration of team coping intentions in different stages. Even if the aim is to tap transactional processes in real-life situations, it might be better to conduct research using a sound-kinetic avatar based collaborative environment than a virtual first-person perspective scenario alone. The VE consisted of two dual-processor PC systems, a video splitter, a digital camera and two stereoscopic CRT displays. The system was programmed in C++ and VRScape Immersive Cluster from VRCO, which created an artificial environment that encodes the user's motion from a video camera, targeted at the face of the users and physiological sensors attached to the body.