Effect of degeneration on bone mineral density, trabecular bone score and CT Hounsfield unit measurements in a spine surgery patient population.

This study investigated the impact of spinal degeneration on bone mineral density (BMD), trabecular bone score (TBS), and CT Hounsfield units in an at-risk population. We found that BMD was increased by degeneration, whereas TBS and HU were unaffected. These findings support that TBS is not adversely affected by spinal degeneration. INTRODUCTION: This study evaluated the impact of spinal degeneration on BMD and TBS measured by dual-energy x-ray absorptiometry (DXA) and on CT HU in a spine surgery patient population. METHODS: A retrospective study of 63 patients referred for consideration of spine surgery or with history of spine surgery was performed. Patients were included if a DXA scan and a CT containing the lumbar spine were obtained within 18 months of each other. DXA data were collected and analyzed by vertebral level. Individual vertebrae were assessed for degenerative changes by qualitative evaluation of the anterior and posterior elements using CT. Degeneration scores were compared to BMD T-scores, TBS and CT HU at individual vertebral levels L1-4, and after applying International Society for Clinical Densitometry (ISCD) criteria for excluding vertebrae from diagnostic consideration. RESULTS: Mean patient age and BMI were 67.2 years and 27.8 kg/m2, respectively; 79.4% were female. Mean (SD) lowest T-scores of the hip, spine, and lowest overall T-score were - 1.3 (1.4), - 1.7 (0.9), and - 1.9 (1.0), respectively. Osteoporosis was present by T-score in 38% and osteopenia in 52%; 10% had a history of osteoporotic fracture. The mean degeneration score of individual vertebrae was 4.1 on a 0-6 scale. T-score correlated moderately with degeneration score (Spearman's rho 0.484, p < 0.001), whereas TBS and HU were unrelated. ISCD excluded vertebrae had a higher degeneration score than included vertebrae (p = < 0.001). CONCLUSIONS: In a spine surgery population, TBS and CT HU values are unrelated to degeneration score and thus appear unaffected by lumbar vertebral degenerative changes. Additionally, these data support the ISCD criteria for vertebral exclusion.

Opportunistic Use of Lumbar Magnetic Resonance Imaging for Osteoporosis Screening.

Magnetic resonance imaging (MRI) is a routine assessment before spine surgery. We found that the opportunistic use of MRI with the vertebral bone quality (VBQ) score has good diagnostic ability, with a threshold value of VBQ > 3.0, in recognizing patients who may need further osteoporosis evaluation. INTRODUCTION: The purpose of this study was to determine whether the opportunistic use of magnetic resonance imaging (MRI) is useful for identifying spine surgical patients who need further osteoporosis evaluation. METHODS: This retrospective study evaluated 83 thoracolumbar spine surgery patients age ≥ 50 who received T1-weighted MRI. Opportunistic MRI was evaluated with the vertebral bone quality (VBQ) score, VBQ (fat) score, and signal-to-noise ratio (SNR). Each uses the median L1-L4 vertebral body signal intensities (SI) divided by either the L3 cerebrospinal fluid (CSF) SI, average SI of the L1 and S1 dorsal fat, or standard deviation (SD) of the background SI dorsal to the skin. Single-level VBQ was calculated as the ratio of the L1 vertebral body and L1 CSF SIs. Receiver-operator curve analysis was performed to determine diagnostic ability. RESULTS: The mean age was 70.10, 80% were female, and 96% were Caucasian. The mean ± SD VBQ, single-level VBQ, VBQ (fat), and SNR were 3.39 ± 0.68, 3.56 ± 0.81, 3.95 ± 1.89, and 113.18 ± 77.26, respectively. Using area under the curve, the diagnostic ability of VBQ, single-level VBQ, VBQ (fat), and SNR for clinical osteoporosis were 0.806, 0.779, 0.608, and 0.586, respectively. Diagnostic threshold values identified with optimal sensitivity and specificity were VBQ of 2.95 and single-level VBQ of 3.06. CONCLUSION: Opportunistic use of MRI is a simple, effective tool that may help recognize patients who are at risk for complications related to bone disease. A VBQ > 3.0 can identify patients who need additional diagnostic evaluation.

Raman spectroscopy insights into the α- and δ-phases of formamidinium lead iodide (FAPbI3).

Solar perovskites have received phenomenal attention and success over the past decade, due to their high power conversion efficiencies (PCE), ease of fabrication and low cost which has enabled the prospect of them being a real commercial contender to the traditional silicon technology. In one of the several developments on the archetypal MAPbI3 perovskite absorber layer, FAPbI3 was found to obtain a higher PCE, likely due to its more optimum band gap, with doping strategies focusing on the inclusion of MA+/Cs+ cations to avoid the unfavourable phase transformation to a photoinactive phase. To better understand the phase change from the photoactive cubic (Pm3[combining macron]m) black (α) phase to the unwanted photoinactive (P63/mmc) yellow (δ) phase, we make use of variable temperature Raman spectroscopy to probe the molecular species and its relationship to the inorganic framework. We show for the first time there to be no Raman active modes for the α phase up to 4000 cm-1, which can be correlated to the Pm3[combining macron]m cubic symmetry of that phase. Our detailed studies suggest that previous reports of the observation of Raman peaks for this phase are likely associated with degradation reactions from the localised laser exposure and the formation of Raman active lead oxide. In addition, we have identified water as a contributing factor to the transformation, and observed a corresponding signal in the Raman spectra, although confirmation of its exact role still remains inconclusive.

The Building Blocks of Battery Technology: Using Modified Tower Block Game Sets to Explain and Aid the Understanding of Rechargeable Li-Ion Batteries.

While Li-ion batteries are abundant in everyday life from smart phones to electric vehicles, there are a lack of educational resources that can explain their operation, particularly their rechargeable nature. It is also important that any such resource can be understood by a wide range of age groups and backgrounds. To this end, we describe how modified tower block games sets, such as Jenga, can be used to explain the operation of Li-ion batteries. The sets can also be utilized to explain more advanced topics such as battery degradation and challenges with charging these batteries at high rates. In order to make the resource more inclusive, we also illustrate modifications to prepare tactile tower block sets, so that the activity is also suitable for blind and partially sighted students. Feedback from a range of groups supports the conclusion that the tower block sets are a useful tool to explain Li-ion battery concepts.

DXA Measured Distal Femur Bone Mineral Density in Patients After Total Knee Arthroplasty: Method Development and Reproducibility.

INTRODUCTION: Total knee arthroplasty (TKA) is increasingly being performed. Distal femur periprosthetic fracture is a potentially catastrophic complication following TKA and existing data document substantial distal femur bone mineral density (BMD) loss following TKA. However, distal femur BMD is virtually never measured clinically as no consensus approach exists. This pilot study's purpose was to define regional BMD variation throughout the femur, suggest standard dual-energy X-ray absorptiometry (DXA) regions of interest (ROIs) and evaluate BMD reproducibility at these ROIs. METHODS: Thirty volunteers 2-5 yr post TKA had both entire femurs imaged twice using a Lunar iDXA with subject repositioning between scans; the atypical femur fracture feature of enCORE software was utilized. To define femoral BMD distribution, custom 1 cm ROIs were stacked one atop the other starting at the intercondylar notch and continuing to the base of the lesser trochanter. Femur length was measured with the ruler tool to calculate distance at 5% increments. ROIs encompassing each 5% increment were utilized to measure BMD at each location. Descriptive statistics were used to determine mean BMD at each ROI and reproducibility at the 15%, 25%, 45%, 60%, and 80% ROIs. RESULTS: The 5 and 10% ROIs included prosthetic and/or patella, causing high BMD values. Distal femur BMD was lowest at the 15% ROI and was higher (p < 0.05) at each more proximal ROI to 45%, then plateaued from 45% to 75%. BMD reproducibility at these regions was excellent; coefficient of variation (CV) from ∼1% to 3.5%. As periprosthetic fractures generally occur in the distal femur, we propose measuring femur BMD using ROIs placed at 15% and 25%. A 60% region could also be used as a highly cortical site. CONCLUSION: Existing DXA capabilities allow distal femur BMD measurement with good reproducibility. Further research using standardized ROIs to assess distal femur BMD loss after TKA, and interventions to mitigate this loss, is indicated.

The American Orthopaedic Association's Own the Bone® database: a national quality improvement project for the treatment of bone health in fragility fracture patients.

The American Orthopaedic Association initiated the Own the Bone (OTB) quality improvement program in 2009. Herein we show that the data collected through this program is similar to that collected in other large studies. Thus, the OTB registry functions as an externally valid cohort for studying fragility fracture patients. INTRODUCTION: The American Orthopedic Association initiated the Own the Bone (OTB) quality improvement program in 2009 to improve secondary prevention of fragility fractures. In this study, we present a summary of the data collected by the OTB program and compare it to data from other large fragility fracture registries with an aim to externally validate the OTB registry. METHODS: The OTB registry contained 35,038 unique cases of fragility fracture as of September, 2016. We report the demographics, presenting fracture characteristics, past fracture history, and bone mineral density (BMD) data and compare these to data from large fragility fracture studies across the world. RESULTS: Seventy-three percent of the patients in the OTB registry were female, Caucasian, and post-menopausal. In 54.4% of cases, patients had a hip fracture; spine fractures were the second most common fracture type occurring in 11.1% of patients. Thirty-four percent of the patients had a past history of fragility fracture, and the most common sites were the spine and hip. The average femoral neck T-score was - 2.06. When compared to other studies, the OTB database showed similar findings with regard to patient age, gender, race, BMI, BMD profile, prior fracture history, and family history of fragility fractures. CONCLUSION: OTB is the first and largest multi-center voluntary fragility fracture registry in the USA. The data collected through the OTB program is comparable to that collected in international studies. Thus, the OTB registry functions as an externally valid cohort for further studies assessing the clinical characteristics, interventions, and outcomes achieved in patients who present with a fragility fracture in the USA.

Validity of height loss as a predictor for prevalent vertebral fractures, low bone mineral density, and vitamin D deficiency.

Many osteoporosis-related vertebral fractures are unappreciated but their detection is important as their presence increases future fracture risk. We found height loss is a useful tool in detecting patients with vertebral fractures, low bone mineral density, and vitamin D deficiency which may lead to improvements in patient care. INTRODUCTION: This study aimed to determine if/how height loss can be used to identify patients with vertebral fractures, low bone mineral density, and vitamin D deficiency. METHODS: A hospital database search in which four patient groups including those with a diagnosis of osteoporosis-related vertebral fracture, osteoporosis, osteopenia, or vitamin D deficiency and a control group were evaluated for chart-documented height loss over an average 3 1/2 to 4-year time period. Data was retrieved from 66,021 patients (25,792 men and 40,229 women). RESULTS: A height loss of 1, 2, 3, and 4 cm had a sensitivity of 42, 32, 19, and 14% in detecting vertebral fractures, respectively. Positive likelihood ratios for detecting vertebral fractures were 1.73, 2.35, and 2.89 at 2, 3, and 4 cm of height loss, respectively. Height loss had lower sensitivities and positive likelihood ratios for detecting low bone mineral density and vitamin D deficiency compared to vertebral fractures. Specificity of 1, 2, 3, and 4 cm of height loss was 70, 82, 92, and 95%, respectively. The odds ratios for a patient who loses 1 cm of height being in one of the four diagnostic groups compared to a patient who loses no height was higher for younger and male patients. CONCLUSIONS: This study demonstrated that prospective height loss is an effective tool to identify patients with vertebral fractures, low bone mineral density, and vitamin D deficiency although a lack of height loss does not rule out these diagnoses. If significant height loss is present, the high positive likelihood ratios support a further workup.

Clinical height measurements are unreliable: a call for improvement.

UNLABELLED: Height measurements are currently used to guide imaging decisions that assist in osteoporosis care, but their clinical reliability is largely unknown. We found both clinical height measurements and electronic health record height data to be unreliable. Improvement in height measurement is needed to improve osteoporosis care. INTRODUCTION: The aim of this study is to assess the accuracy and reliability of clinical height measurement in a university healthcare clinical setting. METHODS: Electronic health record (EHR) review, direct measurement of clinical stadiometer accuracy, and observation of staff height measurement technique at outpatient facilities of the University of Wisconsin Hospital and Clinics. We examined 32 clinical stadiometers for reliability and observed 34 clinic staff perform height measurements at 12 outpatient primary care and specialty clinics. An EHR search identified 4711 men and women age 43 to 89 with no known metabolic bone disease who had more than one height measurement over 3 months. The short study period and exclusion were selected to evaluate change in recorded height not due to pathologic processes. RESULTS: Mean EHR recorded height change (first to last measurement) was -0.02 cm (SD 1.88 cm). Eighteen percent of patients had height measurement differences noted in the EHR of ≥2 cm over 3 months. The technical error of measurement (TEM) was 1.77 cm with a relative TEM of 1.04 %. None of the staff observed performing height measurements followed all recommended height measurement guidelines. Fifty percent of clinic staff reported they on occasion enter patient reported height into the EHR rather than performing a measurement. When performing direct measurements on stadiometers, the mean difference from a gold standard length was 0.24 cm (SD 0.80). Nine percent of stadiometers examined had an error of >1.5 cm. CONCLUSIONS: Clinical height measurements and EHR recorded height results are unreliable. Improvement in this measure is needed as an adjunct to improve osteoporosis care.

Effect of Ga incorporation on the structure and Li ion conductivity of La3Zr2Li7O12.

In this paper we examine the effect of Ga doping on the structure and conductivity of the high Li ion content garnet-related system, La(3)Zr(2)Li(7)O(12). Without Ga doping, La(3)Zr(2)Li(7)O(12) is tetragonal and has low Li ion conductivity. The introduction of Ga leads to a change to a cubic unit cell, and a large enhancement in the conductivity. Prior structural studies of La(3)Zr(2)Li(7)O(12) have shown the presence of both tetrahedral and distorted octahedral sites for Li, and the low conductivity can be explained by the ordered nature of the Li distribution. The present structural study of La(3)Zr(2)Ga(0.5)Li(5.5)O(12) shows that Ga substitutes onto the tetrahedral site. Despite the presence of non-mobile Ga(3+) on the Li sites, the conductivity is enhanced as a result of the introduction of vacancies in the Li sites, and consequent disorder on the Li sublattice. Further work has suggested that over time in air, there is some H(+)/Li(+) exchange, and consequently some variation in the conductivity.

Replicating interbody device subsidence with lumbar vertebraesurrogates.

Bone surrogates are proposed alternatives to human cadaveric vertebrae for assessing interbody device subsidence. A synthetic vertebra with representations of cortices, endplates and cancellous bone was recently developed as an alternative surrogate to polyurethane foam blocks. The ability of the two surrogates to replicate subsidence has not been fully assessed, and was evaluated by indenting them with ring-shaped indenters and comparing their performance with human cadaveric vertebrae using qualitative characteristics and indentation metrics. The sensitivity of each surrogate to a centrally or peripherally placed indenter was of particular interest. Many indentation characteristics of the foam blocks were similar to those of human cadaveric vertebrae, except their insensitivity to centrally and peripherally placed indenters, owing to their homogeneous mechanical properties. This is distinctly different from the cadaveric vertebrae, where a peripherally placed indenter indented significantly less than a centrally placed indenter, because of endplates. By contrast, the synthetic vertebra was sensitive to peripherally placed indenters owing to its bi-material composition, including a thickened peripheral endplate. However, an overly strong synthetic endplate resulted in unrepresentative indentation shape and depth. Both surrogates produced similar results to human cadaveric vertebrae in certain respects, but neither is accurate enough in terms of material property distribution to model subsidence completely in human cadaveric vertebrae.

T2 relaxation times correlated with stage of lumbar intervertebral disk degeneration and patient age.

BACKGROUND AND PURPOSE: T2 relaxation times provide a continuous measure of changes in intervertebral disk biochemistry. The purpose of this study was to correlate T2 relaxation times in lumbar disks with patient age and stage of degeneration. MATERIALS AND METHODS: Sagittal T1- and T2-weighted images and axial images were acquired in 20 patients referred for MR imaging for back pain or radiculopathy. Two readers inspected these images and assigned a Pfirrmann grade to each disk. An additional sagittal multiecho FSE image sequence was obtained, and T2 relaxation times were calculated for a each lumbar disk. T2 relaxation times were correlated with Pfirrmann grade. T2 relaxation times in nondegenerated disks were correlated with patient age. Statistical significance was tested by ANOVA, ad hoc tests, and Pearson coefficients. RESULTS: T2 relaxation times were calculated for 95 lumbar disks in 19 patients and discarded for 5 disks in 1 patient due to motion artifacts. Forty-four disks were classified as Pfirrmann grade II; 34, as grade III; 14, as grade IV; and 3, as grade V. Mean T2 relaxation times of the central region decreased from 108 ms for grade II to 53 ms for grade IV disks. T2 relaxation times correlated significantly with Pfirrmann grade. For grade II disks, T2 relaxation times of the central region decreased significantly from an average of 132 ms for patients in their 20s to 86 ms for those in their 60s. CONCLUSIONS: T2 relaxation times in lumbar disks correlate with stage of degeneration and patient age.

Optimizing nonviral-mediated transfection of human intervertebral disc chondrocytes.

BACKGROUND CONTEXT: The use of viral vectors for transfection of human disc chondrocytes has been well documented. However, because of immunological and cell toxicity concerns, nonviral reagents may provide gene delivery to intervertebral disc (IVD) chondrocytes without these associated obstacles. Several studies have been done using nonviral delivery systems with varying degrees of success. PURPOSE: The purpose of the study was to determine the efficiency, toxicity, and optimal conditions for gene delivery into human degenerative IVD cells via nonviral reagents in vitro. STUDY DESIGN/SETTING: In vitro viral and nonviral gene transfer. PATIENT SAMPLE: Human disc chondrocytes from 21 patients undergoing discectomy for trauma, disc herniation, and fusion for scoliosis or degenerative low back pain. OUTCOME MEASURES: Cell cytotoxicity and transfection efficiency as determined by microscopy, luciferase assay, and flow cytometry. METHODS: Seventeen lipid-based nonviral reagents coupled to DNA plasmids coding for luciferase were transfected into cultured chondrocytes. Cells were transfected with varying ratios of DNA plasmid to reagent, harvested at 48 hours and analyzed for transfection rates and cell viability. Transfections with adenoviral constructs were comparisons. The three most efficient reagents were then coupled to green fluorescent protein and the experiments repeated. The most efficient reagent after these experiments (LT1) was tested in standard chondrocyte-maintenance medium and a minimal medium mixture devoid of antibiotics, buffers, and amino acids. Finally, LT1 in minimal medium with various hyaluronidase treatments was tested. The most effective reagents and relative toxicity as measured by flow cytometry were analyzed using repeated measures analysis of variance. RESULTS: LT1 was most efficient and least toxic of nonviral reagents tested. LT1 had a mean percent survival of 78.1% versus 26.6% for TKO, 15.8% for T-Jurkat, and 70.8% in controls. Transfection was 1.5%. LT1 in minimal medium was significantly better than other reagents for both cell viability and transfection percentages. Minimal medium increased transfection with other reagents, yet cell viability with TKO and T-Jurkat was poor. Hyaluronidase had no effect on the viability of controls and decreased viability from 74.9% to an overall mean of 62.6% for all treatments. Transfection percentages increased from 1.8% without treatment to 15.2% with 40 units and 10.4% with four units of hyaluronidase given 24 hours before transfection and left in throughout the experiment. When treated at the time of transfection, efficiency was not significantly different to samples without hyaluronidase added. Additionally, hyaluronidase added 24 hours before transfection and washed out at the time of transfection significantly increased transfection percentages. CONCLUSIONS: LT1 was the most efficient reagent in terms of transfection ability and cell toxicity compared with other reagents. Treatments in minimal medium yielded significant increases in transfection and no significant difference in toxicity as compared with controls. Hyaluronidase treatments improve transfection significantly but also increase toxicity. These results suggest that the nonviral reagent LT1 can be used to transfect IVD chondrocytes in vitro and may help facilitate gene transfection of IVD chondrocytes in vivo.

Cloning and functional expression of voltage-gated ion channel subunits from cnidocytes of the Portuguese Man O'War Physalia physalis.

Cnidocytes were dissociated from the tentacles of the Portuguese Man O'War Physalia physalis using heat treatment, and purified using density centrifugation. Visual observation confirmed that these cnidocytes contained a nucleus, a cnidocyst and an apical stereocilium, confirming that the cells were intact. A cnidocyte-specific amplified cDNA library was then prepared using RNA isolated from the cnidocytes, and screened for voltage-gated ion channel subunits using conventional molecular cloning techniques. A variety of channel proteins were identified and full-length sequence obtained for two of them, a Ca(2+) channel beta subunit (PpCa(V)beta) and a Shaker-like K(+) channel (PpK(V)1). The location of the transcripts was confirmed by RT-PCR of total RNA isolated from individually selected and rinsed cnidocytes. The functional properties of these two channel proteins were characterized electrophysiologically using heterologous expression. PpCa(V)beta modulates currents carried by both cnidarian and mammalian alpha(1) subunits although the specifics of the modulation differ. PpK(V)1 produces fast transient outward currents that have properties typical of other Shaker channels. The possible role of these channel proteins in the behavior of cnidocytes is discussed.

Silver nitrate in silver zeolite A: three-dimensional incommensurate guest ordering in a zeolite framework.

We report the results of a detailed examination of the occlusion of silver nitrate in silver zeolite A (AgA). The superlattice reported to occur in (AgNO3)9-AgA was found to melt at between 80 and 100 degrees C on heating and reappear when the sample was cooled down to 80 degrees C. Annealing in this temperature range and rigorous exclusion of water produced an enhancement of the superlattice peaks, which results from ordering of the contents of the zeolite cages. Peaks assigned to the superlattice were indexed with the tetragonal lattice parameters a = 17.440(5) and c = 12.398(4) A and proposed space group P4/nmm. The sharp peaks representing the lattice of the framework (a = 12.3711(5) A, Pm3m) remained largely unaffected by the guest in this compound, which was found to exhibit strong negative thermal expansion. The host and guest lattices are incommensurate with the tetragonal guest lattice being slightly larger than the cubic host in the c-direction and slightly smaller in the a- and b-directions.

The value of T2 relaxation times to characterize lumbar intervertebral disks: preliminary results.

BACKGROUND AND PURPOSE: The present standard for staging intervertebral disk degeneration is a discrete scale, consisting usually of 5 stages. The purpose of this pilot study was to investigate the use of T2 measurements as a continuous measure of intervertebral disk degeneration. METHODS: We obtained images in 5 volunteers with a 3D fast spin-echo sequence modified for the purpose of calculating T2 relaxation times from multiple echoes in the echo train. Disks were classified on the basis of conventional criteria into one of the 5 stages of disk degeneration. Average T2 values were calculated for stage II, III, and V disks, which were identified in the volunteers. Differences between the disk levels were analyzed with analysis of variance and differences between stages tested with a Student t test with significance set at the 0.01 level. RESULTS: In the 5 volunteers, 20 stage II, 4 stage III, and a single stage V disk were found. Contour plots showed the highest T2 values in the nucleus pulposus near the vertebral endplates and lower T2 values in the intranuclear cleft region and peripheral annulus fibrosus. Average T2 values were significantly lower in the type III and V disks than in the normal disks. CONCLUSIONS: The study suggests that intervertebral disks can be characterized and classified accurately by means of T2 values. More studies are warranted to determine the range of T2 values for normal disks.

Direct observation of defect levels in InN by soft X-ray absorption spectroscopy.

We have used synchrotron-based near-edge X-ray absorption fine structure (NEXAFS) spectroscopy to study the electronic structure of nitrogen-related defects in InN(0001). Several defect levels within the band gap or the conduction band of InN were clearly resolved in NEXAFS spectra around the nitrogen K-edge. We attribute the level observed at 0.3 eV below the conduction band minimum (CBM) to interstitial nitrogen, the level at 1.7 eV above the CBM to antisite nitrogen, and a sharp resonance at 3.2 eV above the CBM to molecular nitrogen, in full agreement with theoretical simulations.

The Pediatric Heart Network: a primer for the conduct of multicenter studies in children with congenital and acquired heart disease.

Most contemporary diagnostic and treatment strategies for pediatric patients with cardiovascular disease are not supported by evidence from clinical trials but instead are based on expert opinion, single-institution observational studies, or extrapolated from adult cardiovascular medicine. In response to this concern, the National Heart, Lung, and Blood Institute established the Pediatric Heart Disease Clinical Research Network (PHN) in 2001. The purposes of this article are to describe the initiation, structure, and function of the PHN; to review the ongoing studies; and to address current and future challenges. To date, four randomized clinical trials and two observational studies have been launched. Design and conduct of complex, multicenter studies in children with congenital and acquired heart disease must address numerous challenges, including identification of an appropriate clinically relevant primary endpoint, lack of preliminary data on which to base sample size calculations, and recruitment of an adequate number of subjects. The infrastructure is now well developed and capable of implementing complex, multicenter protocols efficiently and recruiting subjects effectively. The PHN is uniquely positioned to contribute to providing evidence-based medicine for and improving the outcomes of pediatric patients with cardiovascular disease.

Comparison of different substances for subureteric injection in the management of vesicoureteric reflux in children.

INTRODUCTION: Endoscopic techniques are becoming increasingly accepted for treatment of vesicoureteric reflux as alternatives to open surgical reimplantation. However, there is some debate about the ideal injectable material. Since we have accumulated experience with several substances, an opportunity existed to compare them. MATERIALS AND METHODS: From 1991 to 2003, 101 children with vesicoureteric reflux were treated by endoscopic subureteric injection either once (74) or twice (27) by either of two pediatric urologists. There were a total of 165 ureteral injections, 83 with polytetrafluoroethylene (Teflon), 73 with polydimethylsiloxane (Macroplastique), and 9 with collagen. Each child was evaluated pre-operatively and 3 months post-operatively with a nuclear cystogram and renal ultrasonography. RESULTS: The polytetrafluoroethylene and polydimethylsiloxane groups were not significantly different with respect to sex, age, indication for surgery, severity of reflux or prior surgeries. The collagen group overall did very poorly with only 3 of 9 refluxing ureters cured. The other two substances had much more success with 61% of ureters in the polytetrafluoroethylene group cured on first injection and 75% with polydimethylsiloxane, plus another 19% and 11% cured on second attempt, respectively (total 80% and 86%). CONCLUSIONS: Subureteric injections of polytetrafluoroethylene and polydimethylsiloxane are very effective at curing vesicoureteric reflux in children with little morbidity. When comparing individual cases, ureters, and all grades of reflux, polytetrafluoroethylene and polydimethylsiloxane have similar success rates. Collagen injections were less successful, and patients with neurogenic bladders had poor results.

Specific sites in the Beta Interaction Domain of a schistosome Ca2+ channel beta subunit are key to its role in sensitivity to the anti-schistosomal drug praziquantel.

Praziquantel, the drug of choice against schistosomiasis, disrupts calcium (Ca2+) homeostasis in schistosomes via an unknown mechanism. Voltage-gated Ca2+ channels are heteromultimeric transmembrane protein complexes that contribute to impulse propagation and also regulate intracellular Ca2+ levels. Beta subunits modulate the properties of the pore-forming alpha1 subunit of high voltage-activated Ca2+ channels. Unlike other Ca2+ channel beta subunits, which have current stimulatory effects, a beta subunit subtype found in S. mansoni (SmbetaA) and S. japonicum (Sjbeta) dramatically reduces current levels when co-expressed with Ca2+ channel alpha1 subunits in Xenopus oocytes. It also confers praziquantel sensitivity to the mammalian Cav2.3 alpha1 subunit. The Beta Interaction Domains (BIDs) of SmbetaA and Sjbeta lack 2 conserved serines that each constitute a consensus site for protein kinase C (PKC) phosphorylation. Here, we use site-directed mutagenesis of schistosome beta subunits to show that these unique functional properties are correlated with the absence of these consensus PKC sites in the BID. Furthermore, a second schistosome beta subunit subtype contains both serines in the BID, enhances currents through alpha1 subunits, and does not confer praziquantel sensitivity. Thus, phosphorylation sites in the BID may play important roles in defining the modulatory properties and pharmacological sensitivities of schistosome Ca2+ channel beta subunits.