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Introduction and hypothesis: Patients with recurrent urinary tract infection (rUTI) have limited knowledge of preventive strategies to lower the risk of UTI. We aimed to develop and test the feasibility of an eHealth system for women with rUTI, named myRUTIcoach, and explored the facilitators and barriers related to its adoption. Methods: We developed myRUTIcoach in a structured iterative process and tested its feasibility among 25 women with rUTI over 2 months. Subsequent questionnaires covered satisfaction, accessibility, and experiences with myRUTIcoach. A random selection of participants and relevant stakeholders took part in semi-structured interviews to explore adoption. Data were analyzed and elaborated using inductive and deductive approaches using the Non-adoption, Abandonment, Spread, Scale-up, and Sustainability (NASSS) framework. Results: MyRUTIcoach was not only widely accepted but also facilitated communication with health care professionals (HCPs) and contributed to greater knowledge of rUTI. Women graded the system a mean of 8.0 (±0.6) out of 10, with 89% stating that they would recommend it to others. Patients indicated that self-management skills were the major facilitators and barriers related to adoption, whereas HCPs stated that the disconnect between myRUTIcoach and electronic health care records (EHRs) was the major barrier. Conclusions: This research describes the development and testing of myRUTIcoach for women with rUTI. Patients and HCPs reported high satisfaction and compliance with myRUTIcoach. However, adoption by the intended users is complex and influenced by all examined domains of the NASSS framework. We have already improved linkage to EHRs, but further optimization to meet patient needs may improve the effectiveness of this self-management tool for rUTI. [ABSTRACT FROM AUTHOR]

Muscarinic receptor antagonists and the β3-agonist mirabegron form the basis of the drug treatment of the overactive bladder syndrome (OAB). The efficacy of muscarinic receptor antagonists and mirabegron are comparable and the combination of solifenacin and mirabegron is moderately more effective than either monotherapy. The side effects of antimuscarinics include dry mouth and constipation and those of mirabegron are similar to placebo. Few patients use these drugs for a longer time due to lack of efficacy and side-effects. No potential drugs with new mechanisms of action seem to be in clinical trials at the moment and there is little chance that this will change in the short term. Because OAB is a symptom complex, with possibly several underlying pathologies and various combinations of symptoms, it is unlikely that new agents will be significantly more effective. The main priorities for the future are not only the discovery of new therapeutic agents, but also identification of subgroups with the same symptomatology or underlying pathology. Biomarkers could play a role in this search. [ABSTRACT FROM AUTHOR]

Background: Previous studies of our group among bipolar offspring and bipolar twins showed significant higher prevalence's and levels of antithyroid peroxidase antibodies (TPO-Abs) in offspring and co-twins (without a mood disorder) compared to controls, suggesting that TPO-Abs might be considered as vulnerability factor (trait marker) for BD development. Objectives: Here we elucidate, in the same cohorts, but now after 12- and 6-year follow-up, whether TPO-abs should be considered as a 'trait' marker for BD. The present study aims to investigate whether TPO-Abs (1) are stable over time, (2) are associated with lithium-exposure, (3) share a common genetic background with BD and are related to psychopathology. Results: In bipolar offspring and twins, the prevalence of TPO-Abs is stable over time ( r = .72 p < .001 resp. r = .82, p < .001) and not associated with lithium use. At follow-up, an increased prevalence of TPO-abs was again observed in bipolar offspring (10,4% versus 4%) and higher TPO-abs titers were still present in co-twins of bipolar cases compared to control twins [mean 1.06 IU/ml (SD .82) versus mean .82 IU/ml (SD .67)], although statistical significance was lost. Conclusions: Although our results show a trend toward an increased inherited risk of the co-occurrence of BD and thyroid autoimmunity, large-scale studies can only draw final conclusions. Nationwide epidemiological and GWAS studies reach such numbers and support the view of a possible common (autoimmune) etiology of severe mood disorders and chronic recurrent infections and autoimmunity, including thyroid autoimmunity. [ABSTRACT FROM AUTHOR]

The Great Salt Plains of Oklahoma is a natural inland terrestrial hypersaline environment that forms evaporite crusts of mainly NaCl. Previous work described the bacterial community through the characterization of 105 isolates from 46 phylotypes. The current report describes the archaeal community through both microbial isolation and culture-independent techniques. Nineteen distinct archaea were isolated, and ten were characterized phenetically. Included were isolates phylogenetically related to Haloarcula, Haloferax, Halorubrum, Haloterrigena, and Natrinema. The isolates were aerobic, non-motile, Gram-negative organisms and exhibited little capacity for fermentation. All of the isolates were halophilic, with most requiring at least 15% salinity for growth, and all grew at 30% salinity. The isolates were mainly mesothermic and could grow at alkaline pH (8.5). A 16S rRNA gene library was generated by polymerase chain reaction amplification of direct soil DNA extracts, and 200 clones were sequenced and analyzed. At 99% and 94% sequence identity, 36 and 19 operational taxonomic units (OTUs) were detected, respectively, while 53 and 22 OTUs were estimated by Chao1, respectively. Coverage was relatively high (100% and 59% at 89% and 99% sequence identity, respectively), and the Shannon Index was 3.01 at 99% sequence identity, comparable to or somewhat lower than hypersaline habitats previously studied. Only sequences from Euryarchaeota in the Halobacteriales were detected, and the strength of matches to known sequences was generally low, most near 90% sequence identity. Large clusters were observed that are related to Haloarcula and Halorubrum. More than two-thirds of the sequences were in clusters that did not have close relatives reported in public databases. [ABSTRACT FROM AUTHOR]

Study design:Postal survey.Objective:To describe the health behaviour of persons with spinal cord injury (SCI) living in the community and the relationships between health behaviour, respondent/injury characteristics, and health-related variables: the presence and number of secondary impairments, readmissions in rehabilitation centre and hospital, and perceived health.Setting:Members of the Dutch Association of Patients with SCI.Methods:The frequency of health behaviours, that delay or prevent secondary impairments, was assessed by means of a 22-item, self-report questionnaire. The questionnaire was also focused on 13 secondary impairments.Results:The frequency of engaging in health behaviour varied considerably between the respondents. Variance was observed between and within the health behaviours measured. The respondents did not frequently engage in pressure relief methods when sitting/driving in their wheelchair. Almost no statistical differences were observed between health behaviour of subgroups of respondents based on respondent/injury characteristics. However, the total health behaviour scores increased significantly with increasing age and pressure sore prevention was significantly more applied in persons with a complete lesion. Health behaviour was significantly more applied in respondents who had one or more secondary impairments.Conclusion:As secondary impairments are prevalent among persons with SCI and education on a healthy lifestyle is a core component of every rehabilitation programme, it is of great importance to rigorously test the efficacy of health behaviours promoted during rehabilitation. Therefore, longitudinal research is recommended.Spinal Cord (2007) 45, 243–249. doi:10.1038/sj.sc.3101967; published online 12 September 2006 [ABSTRACT FROM AUTHOR]

Study design:Systematic review.Objectives:(1) To describe and compare follow-up care programmes, performed by rehabilitation centres, for persons with spinal cord injury (SCI) and (2) to describe the effects of these programmes regarding the occurrence of secondary impairments, well-being, the quality and costs of care.Methods:A systematic literature search was conducted in MEDLINE (1972–2003) and CINAHL (1982–2003). Publications were selected about medical and/or nursing follow-up care to SCI patients living in the community performed by or with rehabilitation facilities for SCI patients. The aim of the follow-up care should be a decrease of secondary impairments, an improvement of well-being, an improvement of the quality and/or a decrease of the costs of care.Results:The search resulted in 24 papers. The descriptions of the programmes in these papers were sometimes rather scattered, vague or brief. The most important methods were telemedicine (six programmes; of which five were performed in the same rehabilitation centre), outpatient consulting hours (six programmes), home visits (three programmes, and case management (one programme). Eight other programmes combined several methods (ie outpatient consulting hours, home visits, peer teaching and support, outings, ongoing support, therapy from several care disciplines, SCI education, providing SCI expertise and support to community health-care providers, coordination of care with community nursing agencies). In all, 16 programmes have been evaluated to some degree. In general the quality of the studies was low. Most evaluations were pre-experimental in design. Only three were quasi-experimental, and two programmes were experimental in design. Although several studies claimed positive effects, it was not possible to draw conclusions on the effect of follow-up care on the occurrence of secondary impairments, well-being, the quality and costs of care.Conclusion:There is a need for the development, the publication and the well-designed evaluation of follow-up care programmes for persons with SCI.Spinal Cord (2005) 43, 462–475. doi:10.1038/sj.sc.3101750; published online 19 April 2005 [ABSTRACT FROM AUTHOR]

FMS-like tyrosine kinase 3 (FLT3) receptor is highly expressed in an array of hematological malignancies including ∼90% of acute myelogenous leukemia (AML). Ligand stimulation of the receptor promotes the survival and proliferation of leukemia cells. Strategies targeting FLT3 using monoclonal antibodies may therefore constitute an effective therapeutic approach for these leukemia. Towards this, we selected a naïve antibody phage display library on both recombinant FLT3 receptor protein and FLT3-expressing leukemia cells using a tailored selection scheme that was designed to isolate antagonistic phage antibodies that not only interfere with receptor/ligand binding but also trigger receptor internalization upon cell surface binding. Phage antibodies were screened first for their ability to bind to cell surface receptor and induce receptor internalization, followed by their activity in blocking ligand–receptor interaction and neutralizing ligand-stimulated receptor activation and cell proliferation. We identified three fully human antibodies, EB10, A2IN, and D4-3, which bound specifically to both soluble and cell surface-expressed FLT3. All three antibodies were shown to be internalized upon binding to cell surface-expressed receptor in a time-dependent fashion. EB10 and D4-3 blocked ligand binding to the receptor with IC50s of 14 and 7 nM, respectively. Further, EB10 and D4-3 inhibited FLT3 ligand-induced receptor phosphorylation and cell proliferation in EOL-1 leukemia cells. Taken together, these results suggest that both EB10 and D4-3 may represent excellent therapeutic candidates for the treatment of FLT3-expressing human leukemia, both as unmodified antibodies and as conjugates of cytotoxic agents.Leukemia (2005) 19, 1432–1438. doi:10.1038/sj.leu.2403825; published online 2 June 2005 [ABSTRACT FROM AUTHOR]

STUDY DESIGN::Cross-sectional survey. OBJECTIVES::(1) To describe the support given to persons with spinal cord injuries (SCI) by their partners, (2) to describe the perceived burden of support by partners and (3) to examine predictors of perceived burden of support. SETTING::The Netherlands. METHODS::All members of the Dutch patients organisation DON (N=1004) and their caregivers, if applicable, were invited. Physical disability of the person with SCI was measured using the Barthel Index (BI). A number of secondary conditions, other practical problems and psychosocial problems were recorded. Partner support was described using a list of ADLsupport, other practical support and emotional support. Burden of support was measured by a six-item measure (Cronbach's alpha 0.92), Nonparametric descriptive statistics and correlations were used. Linear regression was used to identify predictors of caregiver burden. RESULTS::Responses were obtained from 461 persons with SCI. Of 265 couples, patient as well as partner data were available. Mean age of the partners was 49.4 years (SD 12.2) and 69.8%were women. Mean BI of the persons with SCI was12.3 (SD 4.7) on a 0-20 scale and 60.4%were seriously disabled (BI<15). Most partners provided various kinds of support. ADL-support and other practical support were given much more often by partners of persons with serious disability, but less difference was seen regarding emotional support. Professional (paid) support was obtained by 45.3%of all couples. Perceived burden of support was high in 24.8%of partners of persons with serious disabilities against 3.9%of partners of persons with minor disabilities. Significant predictors of caregiver burden were (in order of importance) the amount of ADL support given, psychological problems of the patient, partner age, partner gender, BI score and time after injury (total explained variance 47%). CONCLUSION::A substantial proportion of partners of persons with SCI suffer from serious burden of support. Prevention of caregiver burnout should be part of the lifelong care for persons with SCI.Spinal Cord (2005) 43, 311-319. doi:10.1038/sj.sc.3101704 Published online 1 February 2005 [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) have been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. We recently showed that certain 'liquid' tumors such as leukemia not only produce VEGF, but also express functional VEGFR, resulting in an autocrine loop for tumor growth and propagation. A chimeric anti-VEGFR2 (or kinase insert domain containing receptor, KDR) antibody, IMC-1Cll, was shown to be able to inhibit VEGF-induced proliferation of human leukemia cells in vitro, and to prolong survival of nonobese diabetic-severe combined immune deficient (NOD-SCID) mice inoculated with human leukemia cells. Here we produced two fully human anti-KDR antibodies (IgG1), IMC-2C6 and IMC-1121, from Fab fragments originally isolated from a large antibody phage display library. These antibodies bind specifically to KDR with high affinities: 50 and 200pM for IMC-1121 and IMC2C6, respectively, as compared to 270pM for IMC-1Cll. Like IMC-1Cll, both human antibodies block VEGF/KDR interaction with an ICs0 of approximately 1 nM, but IMC-1121 is a more potent inhibitor to VEGF-stimulated proliferation of human endothelial cells. These anti-KDR antibodies strongly inhibited VEGF-induced migration of human leukemia cells in vitro, and when administered in vivo, significantly prolonged survival of NOD-SCID mice inoculated with human leukemia cells. It is noteworthy that the mice treated with antibody of the highest affinity, IMC-1121, survived the longest period of time, followed by mice treated with IMC-2C6 and IMC-1Cll. Taken together, our data suggest that anti-KDR antibodies may have broad applications in the treatment of both solid tumors and leukemia. It further underscores the efforts to identify antibodies of high affinity for enhanced antiangiogenic and antitumor activities. [ABSTRACT FROM AUTHOR]

In 11 species of the flea beetle genus Longitarsus we investigated whether the insects sequester the pyrrolizidine alkaloids (PAs) present in their host plants of the families Asteraceae and Boraginaceae. In all cases where PAs could be detected in the leaves of the local host plant, they could also be detected in the corresponding beetles. In one host plant, Pulmonaria officinalis, no PAs could be detected in the leaves, yet were present in the beetles collected from them. We suggest this is due to uptake of PAs during the root-feeding larval stage. By comparing the GC-MS pattern of PAs found in the beetles with those of their hosts, we investigated the specificity of this sequestration. Furthermore, we compared the pattern of sequestered PAs across beetle species that had been feeding on the same plant, and across hosts in Longitarsus species that feed on different plants in the field. This allowed us to analyze to what extent the PA pattern in the insects is specific for the beetle species and depends on the local food plant. Our data indicate that the PAs found in the beetles are largely determined by the host plant, e.g., whether alkaloids typical of the Boraginaceae or Asteraceae are present. However, there are some indications for a selective uptake of PAs and apparently the beetles are able to metabolize them. [ABSTRACT FROM AUTHOR]

Physical therapy in ankylosing spondylitis (AS) is considered important for maintaining or improving mobility, fitness, functioning, and global health. We studied the influence of disease duration on the short term effects of supervised individual therapy. One hundred forty-four AS outpatients (modified New York Criteria; mean age: 43 years; median duration of disease: 4 years; range: 0-33) received 12 supervised individual treatments in a 6-week course of 30 minutes. Endpoints were: spinal mobility (thoracic and lumbar flexion and extension, chest expansion, cervical rotation), fitness (maximum work capacity by ergometry), functioning (Sickness Impact Profile (SIP) and the Functional Index (FI)), and global patient assessment of change on a visual analogue scale. After 6 weeks patients had improved in all endpoints, but only significantly in rotation (8 degrees, 10%), fitness (6 watt, 4%), and SIP (0.6, 14%; t-test, p<0.05). Global patient assessment improved by 1.1 (22%). Plots of change scores and disease duration showed no evident relation. We also divided the population into two groups, with the median disease duration as a cut-off. No relevant difference in improvement was found between 'short duration' and 'long duration' groups (t-test of change scores, p>0.05). In addition, no relevant correlation was found between change scores and disease duration (p>0.01). It may be concluded that irrespective of disease duration, short term supervised individual therapy is effective in AS, slightly improving mobility, fitness, functioning and global health. [ABSTRACT FROM AUTHOR]

The metabolism of D- and L-p-fluorophenylalanine (PFP) in DL-PFP resistant and sensitive tobacco cell cultures ( Nicotiana tabacum), cell lines TX4 and TX1, respectively, has been compared. The amino acid analogue was taken up at a lower rate by the resistant cell line TX4. Incorporation of PFP into protein was also considerably reduced in TX4 cells, compared to TX1 cells. This, however, resulted mainly from a diminished availability of PFP due to a more rapid conversion of PFP by TX4 cells. TX1 cells and TX4 cells converted PFP qualitatively in the same way. The only detectable metabolite of D-PFP was N-malonyl-D-PFP, while all metabolites of L-PFP were identified as sequent products of the initial deamination of L-PFP by the enzyme phenylalanine ammonia-lyase (PAL). As TX4 cells were endowed with higher PAL-activity than TX1 cells, the resistant cells were able to metabolize L-PFP more rapidly to give, e.g., p-fluorocinnamoyl glucose ester and p-fluorocinnamoyl putrescine. In the presence of the specific PAL-inhibitor α-aminooxy-β-phenylpropionic acid TX4 cells were slightly more sensitive to PFP. This suggests that the better 'detoxification' contributes to the acquired resistance. The use of PFP as specific indicator for cell lines with increased PAL-activity, and hence increased levels of phenolic compounds, is discussed. [ABSTRACT FROM AUTHOR]

Root cultures of Senecio vulgaris, S. vernalis, S. erucifolius and S. squalidus were established. The patterns of pyrrolizidine alkaloids found in these root cultures were analyzed by high-resolution GC and GC-MS and compared with the alkaloids present in the respective plants. In vitro cultured roots produce alkaloid patterns and accumulate quantities which are comparable to those found in soil grown plants. With the exception of the otonecine derivative senkirkine all pyrrolizidines accumulate as N-oxides. Only senkirkine is partially released into the medium. The cultures incorporate biosynthetic precursors, e.g. C-labelled putrescine or spermidine with high efficiency into the alkaloids. Senecionine N-oxide was found to be the main product of biosynthesis. Evidence is presented that senecionine N-oxide is directly transformed into senkirkine, the main alkaloid of S. vernalis root cultures. [ABSTRACT FROM AUTHOR]

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The extension of the components of anomalous gravity to points outside the globe is usually based on application of Stokes'Gravity Formula and its derivatives, possibly in combination with the use of Poisson's Integral Theorem. The principal deterministic errors in these processes are those due to the effects of unmapped areas where boundary value data are non-existent and those dependent on the treatment of the relatively large uncertainties in zeroth order terms. To reduce these errors significantly below their values in current practices, the following extension procedure has been developed: The radial component is found from where δg is extended by Poisson's Theorem, without removal of zeroth order effects and the anomalous potential T is obtained by the use of a spherical harmonic reference gravity model of degree and order seven and application of Stokes'formula to the residual anomalous gravity, with intentional truncation of the surface integration at the first zero crossing of the Stokes kernel function. The angular components of anomalous gravity or deflections of the vertical are computed explicity as the slopes of the geoidal height surface. The geoidal heights are obtained by dual application of Stokes' formula, while again employing the seventh degree reference model and truncation at the first zero crossing. [ABSTRACT FROM AUTHOR]

When the values of gravity anomalies are given at the geoid, Ag can be calculated at altitude by application of Poisson's integral theorem. The process requires integration of Δg multiplied by the Poisson kernel function over the entire globe. It is common practice to add to the kernel function terms that will ensure removal of any zeroth and first order components of Δg that may be present. The effects of trancating the integration at the boundary of a spherical cap of earth central half angle ψ have been analyzed using an adaptation of Molodenskii's procedure. The extension process without removal terms retains the correct effects of inaccuracies in the constant term of the gravity reference model used in the definition of Δg. Furthermore, the effects of ignoring remote zones or unmapped areas in the integration process are very much smaller for the extension without removal terms than for the commonly used formula with removal terms. For these reasons the Poisson vertical extension process without removal terms is to be preferred over the extension with the zeroth order term removal. Truncation of this process at the point recommended for the Stokes integration, namely, the first zero crossing of the Stokes kernel function, leaves negligible truncation errors. [ABSTRACT FROM AUTHOR]