Cell-free culture supernatant of Lactobacillus curvatus Wikim38 inhibits RANKL-induced osteoclast differentiation and ameliorates bone loss in ovariectomized mice.

This study was conducted to investigate the inhibitory effects of the cell-free culture supernatant of Lactobacillus curvatus Wikim 38 (LC38-CS) on RANKL-induced osteoclast differentiation and bone loss in a mice model of ovariectomy-induced post-menopausal osteoporosis. LC38-CS inhibited the RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by LC38-CS treatment of RANKL-treated BMDMs. In addition, LC38-CS decreased the RANKL-induced activation of the TRAF6/NF-κB/MAPKs axis at the early stage and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. PRMT1 and ADMA levels, new biomarkers for osteoclastogenesis, were decreased by LC38-CS treatment. The administration of LC38-CS increased bone volume and bone mineral density in ovariectomized mice in µ-CT analysis. These findings suggest that LC38-CS inhibited RANKL-induced osteoclast differentiation by the downregulation of molecular mechanisms and exerted anti-osteoporotic effects.

Effects of anti-osteoporosis medications on radiological and clinical results after acute osteoporotic spinal fractures: a retrospective analysis of prospectively designed study.

Effects of anti-osteoporosis medications such as anti-resorptive and anabolic agents on healing of osteoporotic spinal fracture were retrospectively investigated. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented good pain relief. These findings suggest that proper selection of medication could improve initial management of acute osteoporotic spinal fractures (OSFs). INTRODUCTION: Although anti-osteoporosis medications have beneficial effects on prevention of osteoporotic spinal fractures (OSFs), few studies have compared effects of medications on fracture healing following OSFs. Therefore, the purpose of this study was to elucidate the effects of different anti-osteoporosis medications on radiological and clinical outcomes after acute OSFs. METHODS: A total of 132 patients diagnosed with acute OSFs were enrolled and allocated into three groups [group I (n = 39, no anti-osteoporosis medication), group II (n = 66, bisphosphonate), and group III (n = 27, parathyroid hormone (PTH)]. Radiological parameters including magnetic resonance (MR) classification, occurrence of intravertebral cleft (IVC), and clinical outcomes such as numerical rating scale (NRS) and Oswestry disability index were assessed. Risk analyses for IVC and progressive collapse were done along the related factors and medication type. RESULTS: IVC sign was observed in 30 patients. The rate of IVC sign was lower in group III (7.4%) than that in group I (20.5%) or group II (30.3%), although the difference was not statistically significant. Moreover, the degree of NRS improvement was better in group III than that in group I or group II (5.7 vs. 3.1 vs. 3.5, p < 0.001). On multiple regression analysis, mid-portion type fracture in MR classification was a significant risk factor for progressive OSFs. The use of PTH showed significant lower incidences of occurrence of IVC (odds ratio (OR) = 0.160) and increase in height loss (OR = 0.325). CONCLUSIONS: Different anti-osteoporosis medications presented different clinical and radiological results after acute OSFs. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented better clinical outcomes. Proper selection of medication might improve initial management of acute OSFs.

Ultrasound-guided lung sliding sign to confirm optimal depth of tracheal tube insertion in young children.

BACKGROUND: The tip of the tracheal tube should lie at the mid-tracheal level after tracheal intubation in paediatric patients. Auscultation does not guarantee optimal positioning of the tracheal tube. We compared auscultation and the ultrasound-guided lung sliding sign to confirm optimal positioning of the tracheal tube in paediatric patients. METHODS: We studied 74 paediatric patients aged 0-24 months of ASA physical status 1-3 who were scheduled for elective surgery under general anaesthesia. All were randomly assigned to one of two groups: depth of tracheal tube confirmed by auscultation (Group A) or using the ultrasound-guided lung sliding sign (Group S). RESULTS: Optimal positioning of the tracheal tube was observed in 32 of 37 (87%) subjects in Group S and 24 of 37 (65%) subjects in Group A (difference in proportion, 22%; 95% confidence interval, 2-39%; P=0.030). Optimal depth correlated with patient height (adjusted coefficient=0.888, P<0.001). CONCLUSIONS: In paediatric patients younger than 24 months, use of the ultrasound-guided lung sliding sign was more accurate than auscultation for optimal positioning of the tracheal tube. CLINICAL TRIAL REGISTRATION: KCT 0003015.

Development of a standard protocol for quantitative polymerase chain reaction to detect adenovirus 36, which is associated with obesity.

It has been previously reported that adenovirus 36 (Ad36) infection is associated with obesity in humans and other animals. However, there is no clinically available standard protocol to detect Ad36 DNA. In this study, we developed a method for quantitative and rapid detection of Ad36 DNA. Using a TaqMan probe quantitative polymerase chain reaction (qPCR), we identified that the E3 and E4orf1 regions specifically detect Ad36 DNA, because these regions did not show cross reactivity with other types of adenoviruses. The limit of detection was 379 copy/ml and 384 copy/ml for E3 and E4orf1 regions of Ad36, respectively. The %CV (coefficient of variation) for reproducibility of the assay using adenovirus reference material ranged from 1.07-13.02. After we developed the standard protocol to detect Ad36 DNA, we used mouse as a surrogate model to confirm its clinical applicability. We administered Ad36 to mice via intranasal and oral routes, with intraperitoneal administration as the positive control, to analyze the effect of infection route. Ad36 DNA could be detected in lungs, liver, pancreas, and epididymal fat tissue after intraperitoneal injection, whereas it was found only in lungs after intranasal injection. No Ad36 DNA was detectable in any tested organ after oral injection. This indicates that the main route of infection with Ad36 is intranasal, suggesting that Ad36 is a respiratory virus. The standard protocol for qPCR developed in this study is useful for clinical detection of Ad36 DNA. Keywords: adenovirus 36; real-time PCR; obesity.

Transoesophageal echocardiographic evaluation of central venous catheter positioning using Peres' formula or a radiological landmark-based approach: a prospective randomized single-centre study.

BACKGROUND: The lower superior vena cava (SVC), near its junction with the right atrium (RA), is considered the ideal location for the central venous catheter tip to ensure proper function and prevent injuries. We determined catheter insertion depth with a new formula using the sternoclavicular joint and the carina as radiological landmarks, with a 1.5 cm safety margin. The accuracy of tip positioning with the radiological landmark-based technique (R) and Peres' formula (P) was compared using transoesophageal echocardiography. METHODS: Real-time ultrasound-guided central venous catheter insertion was done through the right internal jugular or subclavian vein. Patients were randomly assigned to either the P group (n=93) or the R group (n=95). Optimal catheter tip position was considered to be within 2 cm above and 1 cm below the RA-SVC junction. Catheter tip position, abutment, angle to the vascular wall, and flow stream were evaluated on a bicaval view. RESULTS: The distance from the skin insertion point to the RA-SVC junction and determined depth of catheter insertion were more strongly correlated in the R group [17.4 (1.2) and 16.7 (1.5) cm; r=0.821, P<0.001] than in the P group [17.3 (1.2) and 16.4 (1.1) cm; r=0.517, P<0.001], with z=3.96 (P<0.001). More tips were correctly positioned in the R group than in the P group (74 vs 93%, P=0.001). Abutment, tip angle to the lateral wall >40°, and disrupted flow stream were comparable. CONCLUSIONS: Catheter tip position was more accurate with a radiological landmark-based technique than with Peres' formula. CLINICAL TRIAL REGISTRATION: Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp KCT0001937.

Effective therapeutic strategy for massive retroperitoneal hematoma after conization: arterial embolization and pigtail catheter insertion.

The loop electrosurgical excision procedure (LEEP) is commonly used to remove cervical intraepithelial neoplasia (CIN) because of its safety profile and likelihood of fewer complications. The authors report a rare case of massive retroperitoneal bleeding combined with hypovolemic shock after LEEP conization. Vessel injury was detected by angiographic computed tomography (CT) and embolization of the uterine artery was successfully performed to achieve hemostasis by an intervention radiologist. A pigtail catheter was subsequently inserted for the drainage of the large retroperitoneal hematoma. The patient did not show any further hemorrhage and recovered safely from hypovolemic shock. Th present case demonstrates a successful multidisciplinary and minimal invasive approach to manage retroperitoneal bleeding with uterine artery embolization. Thus, it should be considered a potential treatment option for hemostasis.

Airborne formaldehyde causes skin barrier dysfunction in atopic dermatitis.

BACKGROUND: It remains to be elucidated whether exposure to air pollutants aggravates atopic dermatitis (AD). OBJECTIVES: This study aimed to evaluate the effects of exposure to formaldehyde for 1 h and 2 h on skin barrier function in both the control and the AD groups. METHODS: In 41 patients with AD and 34 healthy children, a provocation test was performed in which two different areas of normal-appearing skin on the forearm were stimulated with airborne formaldehyde at 500 µg m(-3) or placebo for 2 h. We measured transepidermal water loss (TEWL) and skin pH, and calculated the percentage change from baseline. RESULTS: Exposure to formaldehyde increased TEWL in the control group [P < 0·001; median of difference 1·4; interquartile range (IQR) 0·9-1·6] and in the AD group (P < 0·001; median of difference 2·5; IQR 2·0-3·6). The percentage change of TEWL after formaldehyde exposure in the AD group was higher than in the control group (P < 0·001), whereas exposure to placebo showed no differences between both groups. The AD group also demonstrated a higher percentage increase in skin pH after exposure to formaldehyde than the control group (P < 0·001). CONCLUSIONS: Short-term exposure to formaldehyde causes skin barrier dysfunction in both healthy children and children with AD, and this effect is more prominent in children with AD.

Influence of arm position on catheter placement during real-time ultrasound-guided right infraclavicular proximal axillary venous catheterization.

BACKGROUND: Real-time ultrasound-guided infraclavicular proximal axillary venous catheterization is used in many clinical situations and provides the advantages of catheter stabilization, a reduced risk of catheter-related infection, and comfort for the patient without limitation of movement. However, unintended catheter tip dislocation and accidental arterial puncture occur occasionally. This study was designed to investigate the influence of arm position on catheter placement and complications. METHODS: Patients were randomized to either the neutral group (n=240) or the abduction group (n=241). In the neutral group, patients were positioned with the head and shoulders placed in an anatomically neutral position and the arms kept by the side during catheterization. In the abduction group, the right upper arm was abducted at 90° from the trunk during catheterization. After real-time ultrasound-guided catheterization was carried out in the right infraclavicular proximal axillary vein, misplacement of the catheter and all complications were evaluated with ultrasound and chest radiography. RESULTS: The success rate of complete catheterization before evaluating the placement of the catheter was high in both groups (97.1 vs 98.8%, P=not significant). The incidence of accidental arterial puncture was not different (1.7 vs 0%, P=not significant). The incidence of misplacement of the catheter was higher in the neutral group than in the abduction group (3.9 vs 0.4%, P=0.01). There were no complications, such as haemothorax, pneumothorax, or injury to the brachial plexus and phrenic nerve, in either group. CONCLUSIONS: Upper arm abduction may minimize the risk of misplacement of the catheter during real-time ultrasound-guided infraclavicular proximal axillary venous catheterization. CLINICAL TRIAL REGISTRATION: The trial was registered with the Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp. Identifier: KCT0001417.

Effects of low-fat milk consumption on metabolic and atherogenic biomarkers in Korean adults with the metabolic syndrome: a randomised controlled trial.

BACKGROUND: Previous studies of the health effects of low-fat milk or dairy consumption on the metabolic syndrome have yielded inconsistent results. The present study aimed to investigate the effects of low-fat milk consumption on traits associated with the metabolic syndrome, as well as inflammatory and atherogenic biomarkers, in Korean adults with the metabolic syndrome. METHODS: Overweight Koreans with the metabolic syndrome (n = 58) were recruited and randomly assigned to either the low-fat milk or control group. The low-fat milk group was instructed to consume two packs of low-fat milk per day (200 mL twice daily) for 6 weeks, and the control group was instructed to maintain their habitual diet. Clinical investigations were conducted during the screening visit, on study day 0, and after 6 weeks. RESULTS: No significant differences in changes in body mass index, blood pressure, lipid profile and adiponectin levels, as well as levels of inflammatory markers, oxidative stress markers and atherogenic markers, were found between the low-fat milk and control groups. However, compared to the controls, significant favourable decreases in serum soluble vascular adhesion molecule-1 and endothelin-1 levels were found in the 12 subjects with high blood pressure and in the 18 subjects with hypertriglyceridaemia in the low-fat milk group. CONCLUSIONS: The present study did not demonstrate an overall beneficial effect of low-fat milk consumption in subjects with the metabolic syndrome. However, low-fat milk consumption may have a favourable effect on atherogenic markers in subjects with high blood pressure or hypertriglyceridaemia.

Phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer: the PECULIAR study (KCSG 10-17).

BACKGROUND: Pemetrexed has shown a favourable response rate of about 30% with minimal toxicity when used as a single agent for treatment of advanced urothelial carcinoma. This phase II study evaluated the efficacy and safety of pemetrexed plus cisplatin in advanced urothelial carcinoma. METHODS: This multicentre, single-arm, open-label, phase II clinical trial enrolled patients who had advanced urothelial carcinoma, ECOG PS 0-2, and measurable disease. Pemetrexed 500 mg m(-2) with cisplatin 70 mg m(-2) on day 1 were administered every 3 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: A total of 42 patients were enrolled (median age, 66 years; ECOG 0-1, 100%; visceral metastasis, 54.8%; recurrent disease, 57.1%). Twenty-seven partial responses for an ORR of 64.3% (95% CI, 49.2%-77.0%) were documented. Seven patients had stable disease. Median PFS and OS were 6.9 (95% CI, 6.2-7.6) and 14.4 (95% CI, 10.4-18.4) months, respectively. Grade 3 or 4 neutropenia was observed in 28.6% of patients. No patients experienced febrile neutropenia. CONCLUSION: The combination of pemetrexed and cisplatin is active, and well tolerated in patients with advanced urothelial cancer as a first-line treatment.

RandomizEd phase II trial of Sunitinib four weeks on and two weeks off versus Two weeks on and One week off in metastatic clear-cell type REnal cell carcinoma: RESTORE trial.

BACKGROUND: The standard sunitinib schedule, 4 weeks on, followed by 2 weeks off (4/2 schedule), is associated with troublesome toxicities, and maintenance of adequate sunitinib dosing and drug levels, which are essential for achieving an optimal treatment outcome, is challenging. The objective of this study was to investigate the efficacy and safety of an alternative sunitinib dosing schedule of 2 weeks on and 1 week off (2/1 schedule) compared with the standard sunitinib schedule of 4 weeks on and 2 weeks off (4/2 schedule). PATIENTS AND METHODS: In this multicenter, randomized, open-label, phase II trial, treatment-naïve patients with clear-cell type metastatic renal cell carcinoma (mRCC) were randomly assigned to 4/2 or 2/1 schedules after stratification by Memorial Sloan Kettering Cancer Center risk group and the presence or absence of measurable lesions. The primary end point was the 6-month failure-free survival (FFS) rate, determined by intention-to-treat analysis. RESULTS: From November 2007 to February 2014, 76 patients were accrued, and 74 were eligible. FFS rates at 6 months were 44% with the 4/2 schedule (N = 36) and 63% with the 2/1 schedule (N = 38). Neutropenia (all grades, 61% versus 37%; grade 3-4, 28% versus 11%) and fatigue (all grades, 83% versus 58%) were more frequently observed with schedule 4/2. There was a strong tendency toward a lower incidence of stomatitis, hand-foot syndrome, and rash with schedule 2/1. Objective response rates (ORRs) were 47% in schedule 2/1 and 36% in schedule 4/2. With a median follow-up of 30.0 months, the median time to progression (TTP) was 12.1 months in schedule 2/1 and 10.1 months in schedule 4/2. CONCLUSION: Sunitinib administered with a 2/1 schedule is associated with less toxicity and higher FFS at 6 months than a 4/2 schedule, without compromising the efficacy in terms of ORR and TTP (NCT00570882).

Temperature-dependent rheological property changes of thermoplastic gutta-percha root filling materials.

AIM: To compare the penetration resistance (PR) of six thermoplastic gutta-percha (GP) materials against needle penetration at different temperatures. METHODOLOGY: The PR of the following materials based on warm gutta-percha techniques, Beefill GP Cartridge (Beefill), GP Obturator-Hard/Medium/Soft (Dia-H, Dia-M, Dia-S), Obtura (Obtura) and Tactendo Gutta (Tactendo), was measured as a function of temperature change (from 30 °C to 200 °C). The PR was measured using a force gauge, mounted on a motor-driven micrometre stage, which pushed the penetration needle against GP in a glass cylinder at the designated temperatures. Data were analysed using Kruskal-Wallis anova and Duncan's multiple range tests at 5% significance. RESULTS: The mean PR values for all assessed materials ranged from 15.55 MPa to 26.02 MPa at 30 °C, decreased to 0.18-1.61 MPa at 60 °C, and finally reached 0.02-0.12 MPa at 200 °C. The Obtura had the highest PR values at most of the measured temperatures. At 40-60 °C, Obtura had the highest PR value (P < 0.05), and Tactendo had the lowest amongst the tested materials. At 70-200 °C, both the mean PR values and melt flow temperature (MFR) of Obtura, Dia-H and Dia-M were significantly higher than those of other materials (P < 0.05). CONCLUSIONS: The PR values were changed by both the heating temperature and the brand or type of GP materials tested. Each material was associated with drastic decreases before reaching 60 °C in different degrees, and Obtura had the highest PR at most of the measured temperatures.

Gemcitabine-oxaliplatin plus prednisolone is active in patients with castration-resistant prostate cancer for whom docetaxel-based chemotherapy failed.

BACKGROUND: There has been no previous study on the activity of gemcitabine in combination with oxaliplatin (GemOx) for castration-resistant prostate cancer (CRPC). METHODS: The GemOx was preclinically tested for cytotoxic activity in human prostate cancer cell lines. Clinically, patients with CRPC who failed prior docetaxel were treated with gemcitabine 1000 mg m(-2) and oxaliplatin 100 mg m(-2) intravenously every 2 weeks and prednisolone 5 mg orally twice daily. The primary end point was the prostate-specific antigen (PSA) response rate. RESULTS: The GemOx displayed synergistic effects based on Chou and Talalay analysis. In the phase II study, 33 patients were accrued. The median dose of docetaxel exposure was 518 mg m(-2). A total of 270 cycles were administered with a median of eight cycles per patient. A PSA response rate was 55% (95% CI, 38-72) and radiologic response rate was 82% (9 out of 11). With a median follow-up duration of 20.5 months, the median time to PSA progression was 5.8 months (95% CI, 4.4-7.2) and the median overall survival was 17.6 months (95% CI, 12.6-22.6). The most frequently observed grade 3 or 4 toxicities were neutropenia (13%) and thrombocytopenia (13%). CONCLUSIONS: The GemOx is active and tolerable in patients with metastatic CRPC after docetaxel failure (NCT 01487720).

The impact of drug-resistant cytomegalovirus in pediatric allogeneic hematopoietic cell transplant recipients: a prospective monitoring of UL97 and UL54 gene mutations.

BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity in allogeneic hematopoietic cell transplant (alloHCT) recipients. Little is known about the epidemiology of antiviral resistance in the pediatric population. We performed the prospective study to assess the impact of drug-resistant CMV infections in pediatric alloHCT recipients. METHODS: Pediatric alloHCT recipients who developed CMV infection were consecutively enrolled from May 2009 to April 2012. CMV polymerase chain reaction amplification and sequencing analysis for UL97 and UL54 genes were performed at enrollment and during follow-up. RESULTS: In total, 208 sequence data from viruses in 49 recipients were eligible for the final analysis. Resistant CMV infection caused by UL97 and UL54 mutations occurred in 4.1% (2/49) and 2.0% (1/49), respectively. Known UL97 mutations, M460V and C592G, were observed in each of 2 patients. One patient with the M460V UL97 mutation had an additional T700A UL54 mutation. Drug-resistant CMV attributable mortality was 2.0% (1/49). One or more known sequence variants (drug-sensitive) were observed in all 49 patients. Thirty-one (63.3%) and 28 patients (60.9%) already had known UL97 and UL54 sequence variants before antiviral therapy, respectively. CONCLUSION: This study provides comprehensive information on the epidemiology of both UL97 and UL54 variants and mutations in alloHCT recipients.

Effects of sorbent materials on the cryofocusing analysis of gaseous reduced sulphur compounds.

The relative performance of different sorbent materials employed in the cryofocusing (e.g. in cold trap (CT) unit) stage was investigated at sub-ambient temperature by the thermal desorption (TD)-gas chromatography (GC)-pulsed flame photometric detector. To this end, the TD-based calibration of five reduced sulphur compounds (RSC: H2S, CH3SH, CS2, DMS and DMDS) and SO2 was carried out via the Peltier cooling system with five types of sorbent combinations such as two single-bed (Tenax TA and Silica gel) plus three multibed types (a combination of either two from the following three sorbents: Tenax TA, Silica gel and Carbopack B). Relative performance of each of all five CT options, if evaluated in terms of response factors for each compound, demonstrated that each CT composition acts as an important criterion to distinguish detection properties between light and heavy sulphur species. Although the relative response of H2S and CH3 SH was systematically distinguishable between the CT types, that of SO2 was the most complicated to interpret. According to this study, the two CT types consisting of Carbopack B and Silica gel (CS-0.4 and CS-0.6) were the optimum choices for sulphur gas analysis in terms of basic QA parameters (sensitivity, reproducibility and linearity).

In vitro and Lactation Responses in Mid-lactating Dairy Cows Fed Protected Amino Acids and Fat.

The objective of this study was to evaluate the effect of ruminally protected amino acids (RPAAs) and ruminally protected fat (RPF) supplementation on ruminal fermentation characteristics (in vitro) and milk yield and milk composition (in vivo). Fourteen mid-lactating Holstein dairy cows (mean weight 653±62.59 kg) were divided into two groups according to mean milk yield and number of days of postpartum. The cows were then fed a basal diet during adaptation (2 wk) and experimental diets during the treatment period (6 wk). Dietary treatments were i) a basal diet (control) and ii) basal diet containing 50 g of RPAAs (lysine and methionine, 3:1 ratio) and 50 g of RPF. In rumen fermentation trail (in vitro), RPAAs and RPF supplementation had no influence on the ruminal pH, dry matter digestibility, total volatile fatty acid production and ammonia-N concentration. In feeding trial (in vivo), milk yield (p<0.001), 4% fat corrected milk (p<0.05), milk fat (p<0.05), milk protein (p<0.001), and milk urea nitrogen (p<0.05) were greater in cows fed RPAAs and RPF than the corresponding values in the control group. With an index against as 0%, the rates of decrease in milk yield and milk protein were lower in RPAAs and RPF treated diet than those of basal diet group (p<0.05). In conclusion, diet supplemented with RPAAs and RPF can improve milk yield and milk composition without negatively affecting ruminal functions in Holstein dairy cows at mid-lactating.

Phase II trial of everolimus for the treatment of nonclear-cell renal cell carcinoma.

BACKGROUND: We investigated the efficacy of everolimus against nonclear-cell renal cell carcinoma (nccRCC). Patients and methods Patients with nccRCC received 10-mg everolimus once daily until disease progression or unacceptable toxicity. PATIENTS: who had received a VEGF- tyrosine kinase inhibitor (TKI) previously were included. RESULTS: A total of 49 patients were enrolled. Twenty-three patients (46.9%) received prior anti-VEGF agents. A partial response was observed in five patients (10.2%) and stable disease in 25 patients (51.0%). The disease progressed in 16 patients (32.7%) despite the administration of everolimus. Two of the five patients who showed an objective response to everolimus had chromophobe carcinoma, whereas two had papillary carcinoma and one had unclassifiable carcinoma. Thirty-six patients experienced disease progression during follow-up, and the median progression-free survival (PFS) was 5.2 months. Chromophobe RCC patients seemed to have longer PFS than nccRCC patients with the other histological subtypes (P = 0.084). Previous VEGF-TKI treatment did not influence the efficacy of everolimus, and the toxicity profiles were in line with previous reports. CONCLUSION: Everolimus shows certain efficacy against nccRCC, particularly in patients with chromophobe RCC, and prior treatment with a VEGF-TKI appears not influencing the outcome of everolimus therapy in nccRCC patients. ClinicalTrials.gov number NCT00830895.

High-quality Si3N4 circuits as a platform for graphene-based nanophotonic devices.

Hybrid circuits combining traditional nanophotonic components with carbon-based materials are emerging as a promising platform for optoelectronic devices. We demonstrate such circuits by integrating single-layer graphene films with silicon nitride waveguides as a new architecture for broadband optical operation. Using high-quality microring resonators and Mach-Zehnder interferometers with extinction ratios beyond 40 dB we realize flexible circuits for phase-sensitive detection on chip. Hybrid graphene-photonic devices are fabricated via mechanical transfer and lithographic structuring, allowing for prolonged light-matter interactions. Our approach holds promise for studying optical processes in low-dimensional physical systems and for realizing electrically tunable photonic circuits.

Ultrafast and widely tuneable vertical-external-cavity surface-emitting laser, mode-locked by a graphene-integrated distributed Bragg reflector.

We report a versatile way of controlling the unsaturated loss, modulation depth and saturation fluence of graphene-based saturable absorbers (GSAs), by changing the thickness of a spacer between a single layer graphene (SLG) and a high-reflection mirror. This allows us to modulate the electric field intensity enhancement at the GSA from 0 up to 400%, due to the interference of incident and reflected light at the mirror. The unsaturated loss of the SLG-mirror-assembly can be reduced to ∼0. We use this to mode-lock a vertical-external-cavity surface-emitting laser (VECSEL) from 935 to 981 nm. This approach can be applied to integrate SLG into various optical components, such as output coupler mirrors, dispersive mirrors or dielectric coatings on gain materials. Conversely, it can also be used to increase the absorption (up to 10%) in various graphene based photonics and optoelectronics devices, such as photodetectors.

Effects of hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 polymorphisms on fat androstenone level and gene expression in Duroc pigs.

A high level of androstenone in porcine adipose tissue is a major factor contributing to boar taint. Porcine hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (3ß-HSD, also known as HSD3B1) plays a key role in the hepatic metabolism that catalyzes androstenone to ß-androstenol. Therefore, 3ß-HSD is a candidate gene for boar taint. This study aimed to investigate functional 3ß-HSD polymorphisms in Duroc pigs. We found eight single nucleotide polymorphisms (SNPs) in the full-length porcine 3ß-HSD. Four of the SNPs had restriction enzyme sites, and we genotyped them in 147 uncastrated male Duroc pigs using a polymerase chain reaction-restriction fragment length polymorphism method. Pigs with the GG genotype at the g.165262G>A locus (SNP5) had significantly lower androstenone levels than did those with other genotypes (P = 0.030). SNP5 also was associated with differences in 3ß-HSD mRNA levels: pigs with the GG genotype had higher levels than those with other genotypes (P = 0.019). The SNP5 polymorphism could affect the hepatic catabolism of androstenone and consequently impact androstenone accumulation in the adipose tissue. Therefore, SNP5 in the 3ß-HSD of Duroc pigs could be a useful selective marker for decreasing boar taint.