Temporal trends of decabromodiphenyl ether and emerging brominated flame retardants in dust, air and window surfaces of newly built low-energy preschools.

The envelope of low-energy buildings is generally constructed with significant amounts of plastics, sealants and insulation materials that are known to contain various chemical additives to improve specific functionalities. A commonly used group of additives are flame retardants to prevent the spread of fire. In this study, decabromodiphenyl ether (BDE-209) and fourteen emerging brominated flame retardants (BFRs) were analyzed in indoor dust, air and on the window surface of newly built low-energy preschools to study their occurrence and distribution. BDE-209 and decabromodiphenyl ethane (DBDPE) were frequently detected in the indoor dust (BDE-209: <4.1-1200 ng/g, DBDPE: <2.2-420 ng/g) and on window surfaces (BDE-209: <1000-20 000 pg/m2 , DBDPE: <34-5900 pg/m2 ) while the other thirteen BFRs were found in low levels (dust: <0.0020-5.2 ng/g, window surface: 0.0078-35 pg/m2 ). In addition, the detection frequencies of BFRs in the indoor air were low in all preschools. Interestingly, the dust levels of BDE-209 and DBDPE were found to be lower in the environmentally certified low-energy preschools, which could be attributed to stricter requirements on the chemical content in building materials and products. However, an increase of some BFR levels in dust was observed which could imply continuous emissions or introduction of new sources.

Organophosphate flame retardants and plasticizers in indoor dust, air and window wipes in newly built low-energy preschools.

The construction of extremely airtight and energy efficient low-energy buildings is achieved by using functional building materials, such as age-resistant plastics, insulation, adhesives, and sealants. Additives such as organophosphate flame retardants (OPFRs) can be added to some of these building materials as flame retardants and plasticizers. Some OPFRs are considered persistent, bioaccumulative and toxic. Therefore, in this pilot study, the occurrence and distribution of nine OPFRs were determined for dust, air, and window wipe samples collected in newly built low-energy preschools with and without environmental certifications. Tris(1,3-dichloroisopropyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) were detected in all indoor dust samples at concentrations ranging from 0.014 to 10µg/g and 0.0069 to 79µg/g, respectively. Only six OPFRs (predominantly chlorinated OPFRs) were detected in the indoor air. All nine OPFRs were found on the window surfaces and the highest concentrations, which occurred in the reference preschool, were measured for 2-ethylhexyl diphenyl phosphate (EHDPP) (maximum concentration: 1500ng/m2). Interestingly, the OPFR levels in the environmental certified low-energy preschools were lower than those in the reference preschool and the non-certified low-energy preschool, probably attributed to the usage of environmental friendly and low-emitting building materials, interior decorations, and consumer products.

Prediction of clinical progression after radical prostatectomy in a nationwide population-based cohort.

OBJECTIVE: The aim of this study was to create a model for predicting progression-free survival after radical prostatectomy for localized prostate cancer. MATERIAL AND METHODS: The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostate cancer [clinical stage T1c-T2, Gleason score 5-10, N0/NX, M0/MX, prostate-specific antigen (PSA) < 20 ng/ml]. The cohort was split into two: one cohort for model development (n = 3452) and one for validation (n = 1762). BCR was defined as two increasing PSA values of at least 0.2 ng/ml, initiation of secondary therapy, distant metastases or death from prostate cancer. Multivariable Cox proportional hazard regression was applied, predictive performance was assessed using the bootstrap resampling technique to calculate the c index, and calibration of the model was evaluated by comparing predicted and observed Kaplan-Meier 1 year BCR. RESULTS: The overall 5 year progression-free survival was 83% after a median follow-up time of 6.8 years in the development cohort and 7.3 years in the validation cohort. The final model included T stage, PSA level, primary and secondary Gleason grade, and number of positive and negative biopsies. The c index for discrimination between high and low risk of recurrence was 0.68. The probability of progression-free survival ranged from 22% to 97% over the range of risk scores in the study population. CONCLUSIONS: This model is based on nationwide population-based data and can be used with a fair predictive accuracy to guide decisions on clinical follow-up after prostatectomy. An online calculator for convenient clinical use of the model is available at www.npcr.se/nomogram.

Degree of preservation of the neurovascular bundles during radical prostatectomy and urinary continence 1 year after surgery.

BACKGROUND: Many elderly or impotent men with prostate cancer may not receive a bundle-preserving radical prostatectomy as a result of uncertainty regarding the effect on urinary incontinence. OBJECTIVE: We searched for predictors of urinary incontinence 1 yr after surgery among surgical steps during radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: More than 100 surgeons in 14 centers prospectively collected data on surgical steps during an open or robot-assisted laparoscopic radical prostatectomy. At 1 yr after surgery, a neutral third-party secretariat collected patient-reported information on urinary incontinence. After excluding men with preoperative urinary incontinence or postoperative irradiation, data were available for 3379 men. INTERVENTION: Surgical steps during radical prostatectomy, including dissection plane as a measure of the degree of preservation of the two neurovascular bundles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Urinary incontinence 1 yr after surgery was measured as patient-reported use of pads. In different categories of surgical steps, we calculated the percentage of men changing pads "about once per 24 h" or more often. Relative risks were calculated as percentage ratios between categories. RESULTS AND LIMITATIONS: A strong association was found between the degree of bundle preservation and urinary incontinence 1 yr after surgery. We set the highest degree of bundle preservation (bilateral intrafascial dissection) as the reference category (relative risk = 1.0). For the men in the remaining six groups, ordered according to the degree of preservation, we obtained the following relative risks (95% confidence interval [CI]): 1.07 (0.63-1.83), 1.19 (0.77-1.85), 1.56 (0.99-2.45), 1.78 (1.13-2.81), 2.27 (1.45-3.53), and 2.37 (1.52-3.69). In the latter group, no preservation of any of the bundles was performed. The pattern was similar for preoperatively impotent men and for elderly men. Limitations of this analysis include the fact that noise influences the relative risks, due to variations between surgeons in the use of undocumented surgical steps of the procedure, variations in surgical experience and in how the surgical steps are reported, as well as variations in the metrics of patient-reported use of pads. CONCLUSIONS: We found that the degree of preservation of the two neurovascular bundles during radical prostatectomy predicts the rate of urinary incontinence 1 yr after the operation. According to our findings, preservation of both neurovascular bundles to avoid urinary incontinence is also meaningful for elderly and impotent men. PATIENT SUMMARY: We studied the degree of preservation of the two neurovascular bundles during radical prostatectomy and found that the risk of incontinence decreases if the surgeon preserves two bundles instead of one, and if the surgeon preserves some part of a bundle rather than not doing so.

Interobserver variability in the pathological assessment of radical prostatectomy specimens: findings of the Laparoscopic Prostatectomy Robot Open (LAPPRO) study.

OBJECTIVE: The aim of this study was to strengthen the validity of future findings in the Laparoscopic Prostatectomy Robot Open (LAPPRO) study by investigating the extent of interobserver variability between local pathologists and re-evaluating reference pathologists. MATERIAL AND METHODS: LAPPRO is a Swedish prospective study comparing robot-assisted laparoscopic prostatectomy to open retropubic radical prostatectomy. Patients were recruited from 2008 to 2011. A random selection of 289 prostatectomy specimens was re-evaluated, in a blind fashion, by two reference pathologists from a University Hospital in Denmark and compared with original reports from local pathologists. RESULTS: The exact concordance rate of Gleason score (GS) between local and reference pathologists was 56% (Spearman correlation coefficient 0.54). Exact concordance rates (κ value) for pathological tumour stage (pT), extraprostatic extension (EPE), surgical margin status (SMS) and seminal vesicle invasion (SVI) were 87% (0.63), 86% (0.59), 92% (0.76) and 98% (0.82), respectively. In subanalyses for surgical technique, exact concordance rates of GS, pT, EPE, SMS and SVI were 58%, 83%, 84%, 90% and 97%, respectively, for surgical technique 1 (ST1), compared to 55%, 88%, 87%, 93% and 98%, for surgical technique 2 (ST2). In ST1 specimens undergrading of GS by the local pathologists compared to central review was more common than overgrading (26% vs 16%). The inverse relationship was seen in ST2 specimens (14% vs 32%). CONCLUSION: Re-evaluation of randomly selected prostatectomy specimens in the LAPPRO cohort showed comparable results compared to previous studies of this kind. A systematic variation in the assessment of GS exists, attributable to individual differences in judgement between pathologists. Dichotomising GS (≤ 7 vs ≥ 8) overcomes the systematic variation.

Intrathecal neurosteroids and a neurosteroid antagonist: effects on inflammation-evoked thermal hyperalgesia and tactile allodynia.

Neurosteroids regulate neuronal excitability though binding sites associated with the ionotropic γ-aminobutyric acid (GABAA) receptor. We sought to characterize the spinal analgesic actions in rats of two 5α-reduced neurosteroids, allopregnanolone and alphaxalone, on nociceptive processing and to determine whether a putative neurosteroid antagonist attenuates this effect: (3α,5α)-17-phenylandrost-16-en-3-ol (17PA). Intrathecal (IT) injection of allopregnanolone (1-30 µg/10 µL in 20% cyclodextrin) delivered through lumbar catheters produced a dose-dependent analgesia in rats as measured by thermal thresholds in the ipsilateral (inflamed by intraplantar carrageenan) and in the contralateral (un-inflamed paws). Similar observations were made with alphaxalone (30-60 µg in 20% cyclodextrin). Effective doses were not associated with suppressive effects on pinnae, blink or placing and stepping reflex. Effects of allopregnanolone (30 µg) on the normal and hyperalgesic paw were completely prevented by IT 17PA (30 µg). Reversal by IT 17PA of an equi-analgesic dose of alphaxalone occurred only at higher antagonist dosing. These results suggest that a spinal neurosteroid-binding site with which 17PA interacts may regulate spinal nociceptive processing in normal and inflamed tissue.

CD8+ T cell activation predominate early immune responses to hypercholesterolemia in Apoe⁻(/)⁻ mice.

BACKGROUND: It is well established that adaptive immune responses induced by hypercholesterolemia play an important role in the development of atherosclerosis, but the pathways involved remain to be fully characterized. In the present study we assessed immune responses to hypercholesterolemia induced by feeding Apoe-/- mice a high-fat diet for 4 or 8 weeks. RESULTS: The primary immune response in lymph nodes draining the aortic root was an increased expression of interferon (IFN)-γ in CD8(+)CD28(+) T cells, while an activation of IFN-γ expression in CD4(+) T cells was observed only after 8 weeks of high-fat diet. Contrarily, spleen CD4(+) T cells responded with a higher expression of IL-10. Spleen CD8(+) T cells expressed both IFN-γ and IL-10 and showed enhanced proliferation when exposed to Concanavalin A. Plasma levels of IgG and IgM against oxidized LDL did not change, but the level of apolipoprotein B/IgM immune complexes was increased. CONCLUSION: Hypercholesterolemia leads to unopposed activation of Th1 immune responses in lymph nodes draining atherosclerotic lesions, whereas Th1 activation in the spleen is balanced by a concomitant activation of Th2 cells. The activation of CD8(+) T cells implies that hypercholesterolemia is associated with formation of cell autoantigens.