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AbstractAlthough tea contains antioxidant and antibacterial compounds, it has not yet been clinically tested in the context of abnormal vaginal flora. Our aim was to determine the safety and efficacy of vaginal ovule with 2 mg tea extract once-daily for 5-7 days for symptoms of intermediate vaginal flora. This was randomized blinded vehicle-controlled multicenter clinical trial with composite primary endpoint (drop in the Nugent score (NS), vaginal pH, or improvement of subjective symptoms) compared between the active and vehicle arm using Fisheŕs exact test at α=0.05. Wet mounts were taken from 274 participants from 14 centres, 97 + 95 participants fulfilled the inclusion criteria. In the active and vehicle arm, composite scores improved in 51.8 % (43/83) and 38.3 % (31/81) participants, respectively, representing an odds ratio = 1.73 (CI 0.93- 3.23, p=0.082). In all 274 participants, 7 mild adverse reactions were recorded of which 6 occurred in the passive arm. Intention-to-treat analysis showed more frequent improvement of subjective symptoms (p=0.047) and reduction in burning (p=0.006) in the active arm. The results suggest that as little as 2 mg of tea extract have the capacity to relieve subjective symptoms, notably the perception of genital burning. Tolerability of the tea ovule seems at least as good as that of the vehicle alone. Tea extract deserves further evaluation in larger doses.

Polyomavirus BK(BKV) is the cause of polyomavirus‐associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKVviremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMVprevention regimens with routine screening for BKVand CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKVviremia and PVANwas 28% and 5%, respectively. CMV DNAemia developed in 55% and CMVdisease in 6%. Both BKVviremia (42% vs 23% vs 21%, P= .006) and PVAN(12% vs 2% vs 2%, P= .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKVviremia (hazard ratio [HR] = 2.38, P= .002) and PVAN(HR= 4.73, P= .026). In contrast, the risk of subsequent BKVviremia was lower in patients with antecedent CMV DNAemia (HR= 0.50, P= .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKVviremia and PVAN. CMV DNAemia did not represent a risk for BKV. A post hoc analysis of two randomized trials evaluating CMV prevention strategies in kidney transplant recipients suggests an association between valganciclovir prophylaxis and an increased risk of polyomavirus BK viremia and polyomavirus‐associated nephropathy compared to other modalities, such as high‐dose valacyclovir prophylaxis or a pre‐emptive therapy approach. See the editorial by Pape on page 2401.

Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P= .006) and PVAN (12% vs 2% vs 2%, P= .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P= .002) and PVAN (HR = 4.73, P= .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P= .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.

Background Asymptomatic cytomegalovirus (CMV) infection is associated with graft dysfunction and failure. However, no study assessed CMV viral load in terms of the risk for graft failure.Methods In a prospective cohort of kidney transplant recipients, we assessed the impact of CMV DNAemia on the overall graft survival and the incidence of moderate-to-severe interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsy at 36 months. CMV DNAemia was stratified by viral load in whole blood.Results A total of 180 patients transplanted from October 2003 through January 2011 were included and followed for 4 years; 87 (48%) patients received 3-month prophylaxis with valacyclovir and 45 (25%) with valganciclovir; 48 (27%) were managed by pre-emptive therapy. Within 12 months of transplantation, CMV DNAemia developed in 102 (57%) patients with 36 (20%) having a viral load of =2,000 copies/ml. Multivariate Cox analysis identified CMV DNAemia as an independent risk factor for graft loss (hazard ratio 3.42; P=0.020); however, after stratification by viral load, only CMV DNAemia =2,000 copies/ml (hazard ratio 7.62; P<0.001) remained significant. Both early-onset (<3 months; P=0.048) and late-onset (>3 months; P<0.001) CMV DNAemia =2,000 copies/ml were risk factors for graft loss. The incidence of moderate-to-severe IF/TA was not significantly influenced by CMV DNAemia.Conclusions Kidney transplant recipients having CMV DNAemia with a higher viral load irrespective of the time to onset are at increased risk for graft loss.

Nanoscale titanium dioxide (nanoTiO2) is a commercially important nanomaterial used in numerous applications. Experimental studies with nanotitania have documented lung injury and inflammation, oxidative stress, and genotoxicity. Production workers in TiO2manufacturing with a high proportion of nanoparticles and a mixture of other air pollutants, such as gases and organic aerosols, had increased markers of oxidative stress, including DNA and protein damage, as well as lipid peroxidation in their exhaled breath condensate (EBC) compared to unexposed controls. Office workers were observed to get intermittent exposures to nanoTiO2during their process monitoring. The aim of this study was to investigate the impact of such short-term exposures on the markers of health effects in office workers relative to production workers from the same factory. Twenty-two office employees were examined. They were occupationally exposed to (nano)TiO2aerosol during their daily visits of the production area for an average of 14±9 min/day. Median particle number concentration in office workers while in the production area was 2.32×104/cm3. About 80% of the particles were <100 nm in diameter. A panel of biomarkers of lipid oxidation, specifically malondialdehyde (MDA), 4-hydroxy-trans-hexenal (HHE), 4-hydroxy-trans-nonenal (HNE), 8-isoprostaglandin F2α (8-isoprostane), and aldehydes C6−C12, were studied in the EBC and urine of office workers and 14 unexposed controls. Nine markers of lipid oxidation were elevated in the EBC of office employees relative to controls (p<0.05); only 8-isoprostane and C11were not increased. Significant association was found in the multivariate analysis between their employment in the TiO2production plant and EBC markers of lipid oxidation. No association was seen with age, lifestyle factors, or environmental air contamination. The EBC markers in office employees reached about 50% of the levels measured in production workers, and the difference between production workers and office employees was highly significant (p<0.001). None of these biomarkers were elevated in urine. The approach presented here seems to be very sensitive and useful for non-invasive monitoring of employees exposed to air pollutants, including gases, organic aerosols, and nanoTiO2, and may prove useful for routine biomonitoring purposes. Among them, aldehydes C6, C8, C9, and C10appear to be the most sensitive markers of lipid oxidation in similar occupational cohorts. One major challenge with sensitive biomonitoring techniques, however, is their non-specificity and difficulty in interpreting the meaning of their physiological values in the context of chronic disease development and damage-repair kinetics.

X-ray powder diffraction data, unit-cell parameters, and space group for a new memantine analogue of a Platinum (Pt) (II) complex labelled LA-13, C12H24Cl2N2Pt, are reported [a= 8.324(1) Å, b= 27.838(2) Å, c= 7.113(1), ß= 111.25(1), unit-cell volume V= 1536.26 Å3, Z= 4, and space group P21/n]. All measured lines were indexed and are consistent with the P21/nspace group. No detectable impurity was observed.

Angiogenesis is controlled by several regulatory mechanisms, including the Notch and fibroblast growth factor (FGF) signaling pathways. FGF1, a prototype member of FGF family, lacks a signal peptide and is released through an endoplasmic reticulum–Golgi-independent mechanism. A soluble extracellular domain of the Notch ligand Jagged1 (sJ1) inhibits Notch signaling and induces FGF1 release. Thrombin, a key protease of the blood coagulation cascade and a potent inducer of angiogenesis, stimulates rapid FGF1 release through a mechanism dependent on the major thrombin receptor protease-activated receptor (PAR) 1. This study demonstrates that thrombin cleaves Jagged1 in its extracellular domain. The sJ1 form produced as a result of thrombin cleavage inhibits Notch-mediated CBF1/Suppressor of Hairless [(Su(H)]/Lag-1–dependent transcription and induces FGF1 expression and release. The overexpression of Jagged1 in PAR1 null cells results in a rapid thrombin-induced export of FGF1. These data demonstrate the existence of novel cross-talk between thrombin, FGF, and Notch signaling pathways, which play important roles in vascular formation and remodeling.

We previously found that soluble forms of the Notch ligands Jagged1 and Delta1 induced fibroblast growth factor receptor-dependent cell transformation in NIH3T3 fibroblasts. However, the phenotypes of these lines differed, indicating distinct functional differences among these Notch ligands. In the present study, we used allografts to test the hypothesis that NIH3T3 fibroblasts that express soluble forms of Delta1 and Jagged1 accelerate tumorigenicity in vivo. With the exception of the full-length Jagged1 transfectant, all other cell lines, including the control, generated tumors when injected subcutaneously in athymic mice. Suppression of Notch signaling by the soluble ligands significantly increased tumor onset and growth, whereas full-length Jagged1 completely suppressed tumor development. In addition, there were striking differences in tumor pathology with respect to growth kinetics, vascularization, collagen content, size and number of necrotic foci, and invasiveness into the underlying tissue. Further, the production of angiogenic factors, including vascular endothelial growth factor, also differed among the tumor types. Lastly, both Jagged1- and Delta1-derived tumors contained phenotypically distinct populations of lipid-filled cells that corresponded with increased expression of adipocyte markers. The divergence of tumor phenotype may be attributed to ligand-specific alterations in Notch receptor responses in exogenous and endogenous cell populations within the allographs. Our findings demonstrate distinct functional properties for these Notch ligands in the promotion of tumorigenicity in vivo.

Congenital nephrotic syndrome is commonly associated with hypothyroidism. Thyroid hormone supplementation is recommended as standard of care. The hypothyroidism is postulated to occur secondary to chronic massive proteinuria with loss of thyroid binding globulin, thyroid hormone and iodine. Previous reports have indicated that thyroxin may be discontinued following bilateral nephrectomy. We report our experience with one child with congenital nephrotic syndrome, Finnish type, and hypothyroidism who had a high requirement for thyroxin (100-150 μg/d) from infancy to 4 years of age. Hypothyroidism persisted despite bilateral nephrectomy and later following renal transplantation. However, his thyroxin requirement is now substantially lower (62.5 μg/d) at age 14 years. No goiter was detected clinically and antithyroid antibodies were negative. Thyroid ultrasound and 1231 scan revealed a thyroid gland in the anatomically normal location. 1231 uptake was elevated, 18% at 6 hours and 51% at 24 hours (normal values: 3-16% at 6 hours and 8- 25% at 24 hours). Perchlorate was unavailable for a perchlorate washout study. We speculate that this patient may have an intrinsic problem with thyroid hormone synthesis. It is unclear whether this is related or coincidental to the Finnish nephrotic syndrome. We recommend following thyroid functions closely if thyroxin is discontinued following bilateral nephrectomies in Finnish type congenital nephrotic syndrome.

We have previously demonstrated that the expression of the soluble extracellular domain of the transmembrane ligand for Notch receptors, Jagged 1 (sJ1), in NIH 3T3 cells results in the formation of a matrix-dependent chord-like phenotype, the loss of contact inhibition of growth, and an inhibition of pro-alpha 1(I) collagen expression. In an effort to define the mechanism by which sJ1 induces this phenotype, we report that sJ1 transfectants display biochemical and cytoskeletal alterations consistent with the activation of Src. Indeed, cotransfection of sJ1 transfectants with a dominant-negative mutant of Src resulted in the loss of matrix-dependent chord formation and correlated with the restoration of type I collagen expression and contact inhibition of growth. We also report that the sJ1-mediated induction of Src activity and related phenotypes, including chord formation, may result from the inhibition of endogenous Jagged 1-mediated Notch signaling since it was not possible to detect an sJ1-dependent induction of CSL-dependent transcription in these cells. Interestingly, NIH 3T3 cells transfected with dominant-negative (but not constitutively active) mutants of either Notch 1 or Notch 2 displayed a similar Src-related phenotype as the sJ1 transfectants. These data suggest that the ability of sJ1 to mediate chord formation is Src-dependent and requires the repression of endogenous Jagged 1-mediated Notch signaling, which is tolerant to the destabilization of the actin cytoskeleton, a mediator of cell migration.

The Department of Veterans Affairs (VA) is the largest provider of integrated mental health programs in the United States. It delivers psychiatric and substance abuse services to more than 500,000 veterans each year. The Veterans Administration medical service has a reputation as a leader in suicide prevention and intervention. This article discusses various dimensions of suicide, as well as early preventive and diagnostic interventions currently utilized by the VA medical service. Many of these interventions can be applied to the primary care team model in various mental health programs throughout the country. [ABSTRACT FROM AUTHOR]

Small titania particles were generated within the template of a non-ionic surfactant (TX-100) reverse micelle assembly by the sol–gel method from titanium(iv) isopropoxide. Cyclohexane was used as the reaction solvent to form a reverse micelle system with a low water to surfactant ratio. Gelling, i.e., hydrolysis and polycondensation, were observed by means of viscosity measurements. The transparent raw gels obtained were dried under vacuum at 372 K. The dry gels were then either thermally decomposed directly to TiO₂ or the organic content (surfactant) was substantially reduced first by supercritical fluid extraction with CO₂ and then thermally treated. Special attention was paid to the effect of temperature on the extent of crystallisation of individual crystallographic phases of TiO₂. Gels, partly decomposed gels and gels after the supercritical fluid extraction were investigated by XRD, XPS, IR, TPR, thermogravimetry, mass spectrometry, elemental analysis, UV–vis, SEM and extensive gas adsorption measurements. Their properties were related to the structure and other features of the final nanosized TiO₂ particles. The anatase form of TiO₂ with a very high specific surface area and well-developed mesoporous and microporous structure was prepared.

No abstract available for this article.

X-ray powder diffraction data, unit-cell parameters, and space group for a new Ru Cl diamide complex, C36H48N2SO3RuCl, are reported [a= 12.487(4) Å, b= 16.624(5) Å, c = 17.230(3) Å, unit-cell volume V= 3576,79 Å3, Z= 4, and space group P212121]. All measured lines were indexed and are consistent with the P212121space group. No detectable impurity was observed.

X-ray powder diffraction data, unit-cell parameters, and space group for a new chiral Kemp's acid diamide, C21H26N2O3, are reported [a= 16.061(4) Å, b= 14.340(5) Å, c= 8.361(2) Å, ß= 97.678(4)°, unit-cell volume V= 1908,54 Å3, Z= 4, and space group P21]. All measured lines were indexed and found to be consistent with the P21space group. No detectable impurity was observed.

X-ray powder diffraction data, unit-cell parameters, and space group for a novel platinum-based anticancer complex, Pt(C6H10N2)Br2, are presented [a =10.049 (1) Å, b =9.240 (2) Å, c =11.497 (2) Å, ß= 101.945 (3)°, unit-cell volume V= 1044.41 Å3, Z =4, and space group P21/c]. All the measured lines were indexed and are consistent with the P21/cspace group. No detectable impurities were observed.

X-ray powder diffraction data, unit-cell parameters, and space group for a novel platinum-based anticancer complex cis-[dibromo(1R,2R)-1, 2-diaminocyclohexane-?N, ?N']platinum(II), cis-Pt(C6H14N2)Br2, are presented [a= 11.862(4) Å, b= 7.222(3) Å, c= 13.353(2) Å, ß= 97.813(7)°, cell volume V= 1133,36 Å3, Z= 4, space group P21]. All measured lines were indexed and are consistent with the P21space group. No detectable impurities were observed.

The article offers information on practices of charter schools that can be shared across the public school sector in the U.S. Topics discussed include involvement of parents and families in a cooperative model of education, recruiting and retaining students to maintain enrollment and reliable levels of revenue, and leveraging local university graduate students and faculty to teach electives, curriculum alignment and social work services for students.

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