The presence of radiotoxic 210Po and 210Pb in Ukrainian wild medicinal plants and the assessment of related dose and cancer risk.

Herbal plants are considered natural pharmaceuticals but also accumulate chemical elements and compounds at high levels. 210Po and 210Pb are highly radiotoxic and may cause carcinogenesis due to ionizing radiation. Thirteen of the most popular wild-growing herbaceous plant species, mostly included in the European Pharmacopoeia, were collected across Ukraine. 210Po and 210Pb were determined in the medicinal plants, and their radiotoxicity and cancer risk were calculated. The results of 210Po activities measured in herbal raw material ranged from 2.28 Bq kg-1 dw (where dw is dry weight) in herb of common horsetail (Equisetum arvense L.) collected near Lviv to 37.7 Bq kg-1 dw in leaves of common birch (Betula pendula Roth.) from Rava Ruska. The activity concentrations of 210Pb varied from 0.44 Bq kg-1 dw in leaves of common birch from Starokostyantyniv to 28.4 Bq kg-1 dw in leaves of common birch from Mizhhirya. There were statistically significant differences between 210Po and 210Pb content in flowers, leaves, and aerial portions. The studies indicated that the estimated annual effective radiation dose from Ukrainian herbs consumption was low, ranging 5.00-82.6 µSv from 210Po and 0.56-35.8 µSv from 210Pb, while the cancer morbidity and mortality risk ranged from 10-4 to 10-6. The presented data indicated no radiological risk related to using herbal plant materials.

On 210Po and 210Pb in algae diet supplements - The assessed radiation hazard of aquatic superfoods.

Algae are believed to give health benefits. However, the studies showed they contain toxic elements, including radionuclides, and may affect human health. The study presents the values of activity concentrations of 210Po and 210Pb in the algae supplements available worldwide for adults. The activity concentrations (Bq/kg dw) ranged from 0.07 to 14.5 (210Po) and from 0.06 to 8.48 (210Pb). Also, the effective radiation doses and the cancer risk from 210Po and 210Pb decay ingested with analyzed algal supplements have been assessed. The highest values of annual effective doses have been estimated for 210Po in the recommended portion of Spirulina (Arthrospira platensis) from China (59.7 µSv/year) and Diatomaceous earth from the USA (50.4 µSv/year). The cancer morbidity and mortality risk ranged from 10-4 to 10-8. The study indicated the activity concentrations of 210Po and 210Pb were low, and algae supplements for human consumption could be considered safe food.

Comparison of contrast-enhanced videofluoroscopy to unenhanced dynamic MRI in minor patients following surgical correction of velopharyngeal dysfunction.

OBJECTIVES: To compare dynamic magnetic resonance imaging (MRI) with videofluoroscopy (VFS) regarding image quality and assessment of gap size between soft palate (SP) and posterior pharyngeal wall (PPW) in children and adolescents following surgical correction of velopharyngeal dysfunction (VPD). METHODS: Twenty-one patients undergoing unenhanced 3-T MRI and contrast-enhanced VFS were included in this IRB-approved prospective study. The MRI scan protocol comprised refocused gradient-echo sequences in transverse and sagittal planes during speech, with TE 1.97 ms, TR 3.95 ms, flip angle 8°, matrix size 128 × 128, and 5-mm slice thickness. Radial k-space sampling and sliding window reconstruction were used to achieve an image acquisition rate of 28 frames per second (fps). VFS with 30 fps was similarly performed in both planes. Closure of the velopharyngeal port during phonation was evaluated by two experienced radiologists. RESULTS: Eleven (52.4%) patients displayed a complete closure, whereas ten (47.6%) patients showed a post-operative gap during speech. VFS and MRI equally identified the cases with persistent or recurrent VPD. Differences in SP-PPW distance between VFS (3.9 ± 1.6 mm) and MRI (4.1 ± 1.5 mm) were not statistically significant (p = 0.5). The subjective overall image quality of MRI was rated inferior (p < 0.001) compared with VFS, with almost perfect inter-rater agreement (κ = 0.90). The presence of susceptibility artifacts did not limit anatomical measurements. CONCLUSION: Dynamic MRI is equally reliable as VFS to assess persistent or recurrent inadequate velum closure in patients following surgical treatment of VPD. KEY POINTS: • Unenhanced 3-T dynamic MRI and contrast-enhanced videofluoroscopy are equally useful for the identification of patients with incomplete velopharyngeal closure during speech. • MRI using refocused gradient-echo acquisition with radial k-space sampling and sliding window reconstruction generates diagnostic images with 28 frames per second. • MRI can offer a radiation-free alternative to currently established videofluoroscopy for young patients.

Location and Setting of the Mars InSight Lander, Instruments, and Landing Site.

Knowing precisely where a spacecraft lands on Mars is important for understanding the regional and local context, setting, and the offset between the inertial and cartographic frames. For the InSight spacecraft, the payload of geophysical and environmental sensors also particularly benefits from knowing exactly where the instruments are located. A ~30 cm/pixel image acquired from orbit after landing clearly resolves the lander and the large circular solar panels. This image was carefully georeferenced to a hierarchically generated and coregistered set of decreasing resolution orthoimages and digital elevation models to the established positive east, planetocentric coordinate system. The lander is located at 4.502384°N, 135.623447°E at an elevation of -2,613.426 m with respect to the geoid in Elysium Planitia. Instrument locations (and the magnetometer orientation) are derived by transforming from Instrument Deployment Arm, spacecraft mechanical, and site frames into the cartographic frame. A viewshed created from 1.5 m above the lander and the high-resolution orbital digital elevation model shows the lander is on a shallow regional slope down to the east that reveals crater rims on the east horizon ~400 m and 2.4 km away. A slope up to the north limits the horizon to about 50 m away where three rocks and an eolian bedform are visible on the rim of a degraded crater rim. Azimuths to rocks and craters identified in both surface panoramas and high-resolution orbital images reveal that north in the site frame and the cartographic frame are the same (within 1°).

Golden-Angle Radial Sparse Parallel (GRASP) MRI differentiates head & neck paragangliomas from schwannomas.

PURPOSE: The aim of this study was to demonstrate the value of DCE MRI with high spatiotemporal resolution (GRASP) for differentiating paragangliomas and schwannomas in the head and neck. METHODS: In a retrospective PACS search of in total 410 patients who had undergone head & neck GRASP-MRI, we identified 6 patients with biopsy proven cervical paragangliomas (n = 3) and schwannomas (n = 3). Conventional MRI features were evaluated, lesion size was determined. Postprocessing in 4D-GRASP datasets was performed (1) based on reconstructions with a temporal resolution (Tres) of 4.1 s, qualitative time-intensity curve classification and semiquantitative parameter (Tpeak, PH, ERmax and Slopemax) analysis, and (2) voxel-based mapping and qualitative and semiquantitative perfusion modeling based on reconstructions with a Tres of 1.6 s. Additionally, GRASP perfusion analysis was performed in another set of 5 patients with presumed cervical paragangliomas (n = 3) and schwannomas (n = 2) based on conventional imaging criteria and was correlated with conventional imaging findings. Due to the small sample size, both groups were compared qualitatively. RESULTS: In the time intensity curve classification of 4D GRASP reconstructions (Tres 4.1 s), biopsy proven paragangliomas were consistently characterized by a type-III rapid inflow wash-out pattern, compared to a type-I inflow pattern in the schwannoma group. In both temporal resolutions, semiquantitative analysis of time intensity curves demonstrated rapid wash-in, wash-out, and higher peak signal intensities in paragangliomas compared to schwannomas. In 5 presumed (non-biopsy-proven) paragangliomas and schwannomas, time intensity curves improved diagnostic certainty. CONCLUSIONS: Visual time intensity curve classification and semi-quantitative analysis of GRASP-MRI were, in this small retrospective series, sufficient to differentiate cervical paragangliomas from schwannomas. Utilization of this technique may further improve diagnostic confidence in lesions lacking conventional imaging features.

Dynamic Contrast-Enhanced MRI to Differentiate Parotid Neoplasms Using Golden-Angle Radial Sparse Parallel Imaging.

BACKGROUND AND PURPOSE: Conventional imaging frequently shows overlapping features between benign and malignant parotid neoplasms. We investigated dynamic contrast-enhanced MR imaging using golden-angle radial sparse parallel imaging in differentiating parotid neoplasms. MATERIALS AND METHODS: For this retrospective study, 41 consecutive parotid neoplasms were imaged with dynamic contrast-enhanced MR imaging with golden-angle radial sparse parallel imaging using 1-mm in-plane resolution. The temporal resolution was 3.4 seconds for 78.2 seconds and 8.8 seconds for the remaining acquisition. Three readers retrospectively and independently created and classified time-intensity curves as follows: 1) continuous wash-in; 2) rapid wash-in, subsequent plateau; and 3) rapid wash-in with washout. Additionally, time-intensity curve-derived semiquantitative metrics normalized to the ipsilateral common carotid artery were recorded. Diagnostic performance for the prediction of neoplasm type and malignancy was assessed. Subset multivariate analysis (n = 32) combined semiquantitative time-intensity curve metrics with ADC values. RESULTS: Independent time-intensity curve classification of the 41 neoplasms produced moderate-to-substantial interreader agreement (κ = 0.50-0.79). The time-intensity curve classification threshold of ≥2 predicted malignancy with a positive predictive value of 56.0%-66.7%, and a negative predictive value of 92.0%-100%. The time-intensity curve classification threshold of <2 predicted pleomorphic adenoma with a positive predictive value of 87.0%-95.0% and a negative predictive value of 76.0%-95.0%. For all readers, type 2 and 3 curves were associated with malignant neoplasms (P < .001), and type 1 curves, with pleomorphic adenomas (P < .001). Semiquantitative analysis for malignancy prediction yielded an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.73-0.99). Combining time-to-maximum and ADC predicts pleomorphic adenoma better than either metric alone (P < .001). CONCLUSIONS: Golden-angle radial sparse parallel MR imaging allows high spatial and temporal resolution permeability characterization of parotid neoplasms, with a high negative predictive value for malignancy prediction. Combining time-to-maximum and ADC improves pleomorphic adenoma prediction compared with either metric alone.

Safety and psychological impact of sailing adventure therapy among Veterans with substance use disorders.

OBJECTIVES: Many Veterans suffer from substance use disorders (SUDs). Treatment challenges include poor treatment engagement and high relapse rates. Complementary interventions have the potential to enhance both. This study was a preliminary evaluation of sailing adventure therapy (SAT) for this population. DESIGN: Retrospective chart review. Participants in the intervention were 22 Veterans (20 male, 2 female) aged 22-65 who entered a Veterans Administration residential SUD treatment program. All subjects had two or more SUDs, and many had psychiatric (95%) and/or medical (77%) comorbidities. The age, gender and diagnosis-matched control group (n = 22) received residential SUD treatment as usual (TAU) in the same program but without SAT. SETTING: Residential SUD treatment program at a Veterans Administration Medical Center. INTERVENTION: Sailing adventure therapy. MAIN OUTCOME MEASURES: Positive and Negative Affect Schedule (PANAS), State Trait Anxiety Inventory six-item short form (STAI: Y-6 item), Acceptance and Action Questionnaire II (AAQ II), Five Facet Mindfulness Questionnaire (FFMQ) and a locally developed patient survey. Outcome comparison among SAT plus TAU group versus TAU - only group included measures of successful completion of residential SUD treatment program as well as psychiatric hospitalizations and/or residential SUD treatment program readmissions within 12 months. RESULTS: Neither physical injuries nor increases in anxiety or negative affect occurred, as measured by the PANAS (positive change, p = 0.351; negative change, p = 0.605) and the STAI: Y-6 item (p = 0.144) respectively. There was no significant change in FFMQ (p = 0.580) but a significant increase occurred in AAQ II scores (p = 0.036) indicating an increase in psychological flexibility. Survey responses indicated the participants perceived the experience to be both pleasurable and calming. The preliminary outcome evaluation revealed a significant between-group difference (X2 = 5.34, DF = 1, p = 0.02, r = 0.35) indicating participating in SAT was associated with a greater likelihood of successfully completing residential SUD treatment. However, there were no significant between-group differences in number of psychiatric hospitalizations (X2 = 1.09, DF = 1, p = 0.29, r = 0.16) or residential substance abuse treatment program readmissions (X2 = 0.23, DF = 1, p = 0.64, r = 0.07) in the 12 months after discharge from the program. CONCLUSIONS: Preliminary evidence suggests that SAT is physically safe and not associated with increased anxiety or negative affect. Participant's perceptions of the experience were positive. Preliminary outcome measures suggest associations between participation in SAT and increased psychological flexibility as well as successful completion of a residential SUD treatment program. Further research is indicated to determine whether SAT may be developed as an effective complementary intervention for Veterans with SUDs.

Ethical Use and Impact of Participatory Approaches to Research in Post-Disaster Environments: An Australian Bushfire Case Study.

This paper presents a case study of Beyond Bushfires, a large, multisite, mixed method study of the psychosocial impacts of major bushfires in Victoria, Australia. A participatory approach was employed throughout the study which was led by a team of academic investigators in partnership with service providers and government representatives and used on-site visits and multiple methods of communication with communities across the state to inform decision-making throughout the study. The ethics and impacts of conducting and adapting the approach within a post-disaster context will be discussed in reference to theories and models of participatory health research. The challenges of balancing local interests with state-wide implications will also be explored in the description of the methods of engagement and the study processes and outcomes. Beyond Bushfires demonstrates the feasibility of incorporating participatory methods in large, post-disaster research studies and achieving rigorous findings and multilevel impacts, while recognising the potential for some of the empowering aspects of the participatory experience to be reduced by the scaled-up approach.

Role of High-Resolution Dynamic Contrast-Enhanced MRI with Golden-Angle Radial Sparse Parallel Reconstruction to Identify the Normal Pituitary Gland in Patients with Macroadenomas.

BACKGROUND AND PURPOSE: Preoperative localization of the pituitary gland with imaging in patients with macroadenomas has been inadequately explored. The pituitary gland enhancing more avidly than a macroadenoma has been described in the literature. Taking advantage of this differential enhancement pattern, our aim was to evaluate the role of high-resolution dynamic MR imaging with golden-angle radial sparse parallel reconstruction in localizing the pituitary gland in patients undergoing trans-sphenoidal resection of a macroadenoma. MATERIALS AND METHODS: A retrospective study was performed in 17 patients who underwent trans-sphenoidal surgery for pituitary macroadenoma. Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were obtained. Using an ROI-based method to obtain signal-time curves and permeability measures, 3 separate readers identified the normal pituitary gland distinct from the macroadenoma. The readers' localizations were then compared with the intraoperative location of the gland. Statistical analyses were performed to assess the interobserver agreement and correlation with operative findings. RESULTS: The normal pituitary gland was found to have steeper enhancement-time curves as well as higher peak enhancement values compared with the macroadenoma (P < .001). Interobserver agreement was almost perfect in all 3 planes (κ = 0.89). In the 14 cases in which the gland was clearly identified intraoperatively, the correlation between the readers' localization and the true location derived from surgery was also nearly perfect (κ = 0.95). CONCLUSIONS: This study confirms our ability to consistently and accurately identify the normal pituitary gland in patients with macroadenomas with the golden-angle radial sparse parallel technique with quantitative permeability measurements and enhancement-time curves.

High-Resolution DCE-MRI of the Pituitary Gland Using Radial k-Space Acquisition with Compressed Sensing Reconstruction.

BACKGROUND AND PURPOSE: The pituitary gland is located outside of the blood-brain barrier. Dynamic T1 weighted contrast enhanced sequence is considered to be the gold standard to evaluate this region. However, it does not allow assessment of intrinsic permeability properties of the gland. Our aim was to demonstrate the utility of radial volumetric interpolated brain examination with the golden-angle radial sparse parallel technique to evaluate permeability characteristics of the individual components (anterior and posterior gland and the median eminence) of the pituitary gland and areas of differential enhancement and to optimize the study acquisition time. MATERIALS AND METHODS: A retrospective study was performed in 52 patients (group 1, 25 patients with normal pituitary glands; and group 2, 27 patients with a known diagnosis of microadenoma). Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were evaluated with an ROI-based method to obtain signal-time curves and permeability measures of individual normal structures within the pituitary gland and areas of differential enhancement. Statistical analyses were performed to assess differences in the permeability parameters of these individual regions and optimize the study acquisition time. RESULTS: Signal-time curves from the posterior pituitary gland and median eminence demonstrated a faster wash-in and time of maximum enhancement with a lower peak of enhancement compared with the anterior pituitary gland (P < .005). Time-optimization analysis demonstrated that 120 seconds is ideal for dynamic pituitary gland evaluation. In the absence of a clinical history, differences in the signal-time curves allow easy distinction between a simple cyst and a microadenoma. CONCLUSIONS: This retrospective study confirms the ability of the golden-angle radial sparse parallel technique to evaluate the permeability characteristics of the pituitary gland and establishes 120 seconds as the ideal acquisition time for dynamic pituitary gland imaging.

Methodology for the evaluation of the Stephanie Alexander Kitchen Garden program.

ISSUES ADDRESSED: Community and school cooking and gardening programs have recently increased internationally. However, despite promising indications, there is limited evidence of their effectiveness. This paper presents the evaluation framework and methods negotiated and developed to meet the information needs of all stakeholders for the Stephanie Alexander Kitchen Garden (SAKG) program, a combined cooking and gardening program implemented in selectively funded primary schools across Australia. METHODS: The evaluation used multiple aligned theoretical frameworks and models, including a public health ecological approach, principles of effective health promotion and models of experiential learning. The evaluation is a non-randomised comparison of six schools receiving the program (intervention) and six comparison schools (all government-funded primary schools) in urban and rural areas of Victoria, Australia. A mixed-methods approach was used, relying on qualitative measures to understand changes in school cultures and the experiential impacts on children, families, teachers, parents and volunteers, and quantitative measures at baseline and 1 year follow up to provide supporting information regarding patterns of change. RESULTS: The evaluation study design addressed the limitations of many existing evaluation studies of cooking or garden programs. The multistrand approach to the mixed methodology maintained the rigour of the respective methods and provided an opportunity to explore complexity in the findings. Limited sensitivity of some of the quantitative measures was identified, as well as the potential for bias in the coding of the open-ended questions. CONCLUSION: The SAKG evaluation methodology will address the need for appropriate evaluation approaches for school-based kitchen garden programs. It demonstrates the feasibility of a meaningful, comprehensive evaluation of school-based programs and also demonstrates the central role qualitative methods can have in a mixed-method evaluation. So what? This paper contributes to debate about appropriate evaluation approaches to meet the information needs of all stakeholders and will support the sharing of measures and potential comparisons between program outcomes for comparable population groups and settings.

PI3K regulation of the SKP-2/p27 axis through mTORC2.

The cyclin-dependent kinase inhibitor p27 is a key regulator of cell-cycle progression. Its expression and localization are altered in several types of malignancies, which has prognostic significance in cancers such as renal cell carcinoma (RCC). S-phase kinase-associated protein 2 (SKP-2) is an F-box protein that is part of the SKP-1/Cul1/F-box ubiquitin ligase complex that targets nuclear p27 among many other cell-cycle proteins for proteosomal degradation. Its overexpression has been observed in several tumor types. Signaling by phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) has previously been shown to regulate the SKP-2/p27 axis. Recent evidence suggests that PI3K signaling may activate mammalian target of rapamycin complex 2 (mTORC2) activity. As PI3K signaling is known to regulate SKP-2 and p27, we sought to determine whether these effects were mediated by mTORC2. Here we provide additional genetic evidence that PI3K signaling activates mTORC2 kinase activity. We also demonstrate a novel role for mTORC2 in the modulation of nuclear p27 levels. In particular, mTORC2 signaling promotes the reduction of nuclear p27 protein levels through the increased protein expression of SKP-2. These are the first data to demonstrate a role for mTOR in the regulation of SKP-2. In concordance with these findings, mTORC2 activity promotes cell proliferation of RCC cells at the G1-S interphase of the cell cycle. Collectively, these data implicate mTORC2 signaling in the regulation of the SKP-2/p27 axis, a signaling node commonly altered in cancer.

Stabilization of HIF-2α through redox regulation of mTORC2 activation and initiation of mRNA translation.

Hypoxia inducible factor-2α (HIF-2α) has a critical role in renal tumorigenesis. HIF-2α is stabilized in von Hippel-Lindau (VHL)-deficient renal cell carcinoma through mechanisms that require ongoing mRNA translation. Mammalian target of rapamycin (mTOR) functions in two distinct complexes: Raptor-associated mTORC1 and Rictor-associated mTORC2. Rictor-associated mTORC2 complex has been linked to maintaining HIF-2α protein in the absence of VHL; however, the mechanisms remain to be elucidated. Although Raptor-associated mTORC1 is a known key upstream regulator of mRNA translation, initiation and elongation, the role of mTORC2 in regulating mRNA translation is not clear. Complex assembly of the mRNA cap protein, eukaryotic translation initiation factor 4 (eIF4)E, with activators (eIF4 gamma (eIF4G)) and inhibitors (eIF4E-binding protein 1 (4E-BP1)) are rate-limiting determinants of mRNA translation. Our laboratory has previously demonstrated that reactive oxygen species, mediated by p22(phox)-based Nox oxidases, are enhanced in VHL-deficient cells and have a role in the activation of Akt on S473, a site phosphorylated by the mTORC2 complex. In this study, we examined the role of Rictor-dependent regulation of HIF-2α through eIF4E-dependent mRNA translation and examined the effects of p22(phox)-based Nox oxidases on TORC2 regulation. We demonstrate for the first time that mTORC2 complex stability and activation is redox sensitive, and further defined a novel role for p22(phox)-based Nox oxidases in eIF4E-dependent mRNA translation through mTORC2. Furthermore, we provide the first evidence that silencing of p22(phox) reduces HIF-2α-dependent gene targeting in vitro and tumor formation in vivo. The clinical relevance of these studies is demonstrated.

How common are motor problems in children with a developmental disorder: rule or exception?

BACKGROUND: Few co-morbidity studies have been conducted since the Leeds Consensus Statement on developmental co-ordination disorder (DCD) in 2006. In this Statement, international cut-offs and inclusion criteria were agreed and consequently, the status of DCD changed. Furthermore, most existing co-morbidity studies are small clinical studies, rather than epidemiological studies, resulting in a broad range of co-morbidity rates. DCD has a higher incidence for boys in comparison with girls; questions arise if this preponderance remains the same in combination with other developmental disorders. Therefore, in this study we aimed to determine co-morbidity and gender differences of motor problems in children with a pervasive developmental disorder, a hyperkinetic disorder and/or a speech, language or learning disability. METHODS: Profiles of 3608 children (mean age: 9 years 1 month) referred to rehabilitation centres for behavioural, developmental and sensorineural disorders were studied. RESULTS: Motor problems were reported in one-fifth of the total sample. Co-morbidity of motor problems in specific disorders varied from almost one-fourth to more than one-third. The male/female ratio was significantly higher in children with motor problems and two or more other disorders, compared with children with motor problems and less than two other disorders. CONCLUSIONS: This study indicates that co-morbidity of motor problems with other clinical disorders is not exceptional and developmental deviance is seldom specific to one domain. However, current co-morbidity studies tend to overestimate the number of children with motor problems. In addition, there may be different patterns of symptoms between the genders. These findings stress the importance of assessing motor skills in children with various developmental disorders.

Ablation of the gene encoding p66Shc protects mice against AGE-induced glomerulopathy by preventing oxidant-dependent tissue injury and further AGE accumulation.

AIMS/HYPOTHESIS: AGEs have been implicated in renal disease associated with ageing, diabetes and other age-related disorders. Reactive oxygen species (ROS) promote formation of AGEs, which cause AGE-receptor-mediated ROS generation with activation of signalling pathways leading to tissue injury and further AGE accumulation. ROS generation is regulated by the Src homology 2 domain-containing transforming protein C1 (Shc1) isoform p66(Shc), whose deletion has been shown to protect from tissue injury induced by ageing, diabetes, hyperlipidaemia and ischaemia-reperfusion by preventing oxidative stress. This study was aimed at assessing the role of p66(Shc) in the modulation of oxidative stress and oxidant-dependent renal injury induced by AGEs. METHODS: For 10 weeks, male p66 (shc) knockout (KO) and wild-type (WT) mice were injected with 60 microg/day albumin modified or unmodified by N epsilon-(carboxymethyl) lysine (CML). Mice were then killed for the assessment of renal function and structure, as well as systemic and renal tissue oxidative stress. RESULTS: Upon CML injection, KO mice, in contrast to WT mice, showed no or only mild forms of proteinuria, glomerular hypertrophy, mesangial expansion, glomerular sclerosis, renal/glomerular cell apoptosis and extracellular matrix upregulation. Moreover, KO mice had lower circulating and tissue AGEs than WT mice and unchanged plasma isoprostane 8-epi-prostaglandin-F(2alpha) levels, renal/glomerular CML, 4-hydroxy-2-nonenal, AGE receptor and NAD(P)H oxidase 4 (NOX4) content (and expression of the corresponding genes), and nuclear factor kappaB activation (NFkappaB). Mesangial cells from KO mice exposed to CML showed no or slight increase in ROS levels and NFkappaB activation, again at variance with WT cells. CONCLUSIONS/INTERPRETATION: These data indicate that p66(Shc) participates in the pathogenesis of AGE-dependent glomerulopathy by mediating AGE-induced tissue injury and further AGE formation through ROS-dependent mechanisms involving NFkappaB activation and upregulation of Nox4 expression and NOX4 production.

Clinical evaluation of a viscoelastic gel for reduction of adhesions following gynaecological surgery by laparoscopy in Europe.

BACKGROUND: Commonly used adhesion prevention devices either cannot be applied or are difficult to use via laparoscopy. A viscoelastic gel was developed specifically for adhesion prophylaxis during minimally invasive surgery. METHODS: Randomized, third party-blinded, parallel-group design conducted at four centres. Patients (18-46 years old) underwent laparoscopic surgery with second look 6-10 weeks later. Viscoelastic gel coated adnexa and adjacent tissues. Blinded reviews of videotapes were quantified by American Fertility Society (AFS) adhesion scores. RESULTS: In 25 treatment patients, surgery was performed on 45 adnexa. Coverage of surgical sites at risk for adhesions was typically accomplished with approximately 15 ml of viscoelastic gel which was delivered in approximately 90 s. In 24 control patients, surgery alone was performed on 41 adnexa. Treated adnexa showed a decrease in AFS score (11.9-9.1). In contrast, control adnexa showed an increase in AFS score (8.8-15.8). This difference in second-look AFS scores (42% reduction) is significant (P<0.01). Ninety-three per cent of treated adnexa did not have a worse adhesion score in contrast to 56% of control adnexa. Combining scores into prognostic categories also show significant treatment effect of the viscoelastic gel (P<0.01). CONCLUSION: Viscoelastic gel was easy to use via laparoscopy and produced significant reduction in adnexal adhesions. It provides benefits to patients undergoing gynaecological surgery.

Metabolic changes detected by microdialysis during endotoxin shock and after endotoxin preconditioning.

OBJECTIVE: Preconditioning with low doses of endotoxin has been shown to induce endotoxin hyporesponsiveness. The present study was designed to assess the metabolic response of various tissues during endotoxemia and after pretreatment with endotoxin. DESIGN: Controlled experimental animal study. SETTING: Research laboratory of a university hospital. MEASUREMENTS AND RESULTS: Ten pigs were randomly assigned to a control ( n = 5) or a treatment group ( n = 5), the latter receiving incremental doses of endotoxin 5-2 days prior the experiments. Apart from hemodynamics and oxygen transport variables, lactate, glucose, and glycerol were measured in muscle, subcutaneous fat, and hepatic tissue using microdialysis. Endotoxin was infused (1 micro g.kg.h) until the animals died. A significant increase in tissue lactate (eightfold) and glycerol (fivefold) was observed in the control animals. This effect was almost completely abolished in the endotoxin pretreated group. Endotoxin pretreatment had no significant effects on mean arterial pressure [56 (range 34-89) mmHg vs 70 (47-88) mmHg, n.s.] or cardiac output [4.8 (3.0-5.9) l/min vs 3.2 (2.1-4.2) l/min, n.s.], but significantly improved arterial pO(2) and pH ( P<0.05). Increase of oxygen extraction was higher in control animals [from 34% (range 24-47%) to 72% (range 61-79%)] compared to the pretreatment group [from 30% (range 22-42%) to 44% (range 34-50%), P<0.05]. Endotoxin pretreatment increased survival time from 5.3 h (5.0-5.8) to 8.0 h (7.0-8.5) ( P<0.05), respectively. CONCLUSIONS: Microdialysis monitoring revealed that endotoxin preconditioning ameliorates the increase in tissue metabolism during endotoxemia, accompanied by decreased systemic oxygen demand despite unchanged global hemodynamics.