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Elastin arteriopathy-associated supravalvar pulmonary stenosis is characterized by a thick intraluminal ringlike obstruction at the sinotubular junction of the pulmonary valve. Extension of disease into the branch pulmonary arteries is common. A three-sinus pulmonary trunk augmentation combined with bilateral branch pulmonary augmentation is presented. This approach normalizes the pulmonary trunk and allows optimal augmentation of the central pulmonary arteries., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A generalized strategy for developing a hybrid two-dimensional nanostructured dual T 1 -T 2 MRI contrast agent (CA), by co-loading graphene oxide with both Mn-doped Fe 3 O 4 (T 2 agent) and MnO (T 1 agent) magnetic nanoparticles, is reported. Typical T 1 /T 2 signal quenching, due to magnetic coupling, was not observed because of the fair T 1 CA separation distance from the T 2 CA on the graphene oxide. The resultant two-dimensional nanostructured MRI CA complements the existing dual T 1 -T 2 MRI CA libraries.

Water dispersible two-dimensional magnetic nanocomposites are formed by phase-transferring hydrophobic manganese-doped ferrite nanoparticles (MFPs) into aqueous solvent using a one-step simple approach involving only graphene oxide (GO) as the phase transfer agent. The resultant hydrophilic magnetic nanocomposites (MFNs) are surprisingly stable in the aqueous phase despite its large hydrodynamic size (dhyd). Because of its unique construct that promotes water accessibility towards the MFP core, large MFNs loaded with an 18 nm MFP core (MFN-18; dhyd = 577.9 nm) exhibits transverse relaxivity (r2) up to ∼6.8 times (r2 = 800.8 mM [Mn + Fe](-1) s(-1)) higher than the typical individually coated MFP-18 with amphiphilic brush copolymers (r2 = 117.3 mM [Mn + Fe](-1) s(-1)). Meanwhile, the overall nanocomposites dhyd can be further reduced by employing a smaller pre-sonicated GO sheet phase transfer agent. As a result of using small GO sheets with enhanced hydrophilicity, the r2 of small MFN-18* nanocomposites (dhyd = 224.9 nm) increases by approximately 37% (r2 = 1097.4 mM [Mn + Fe](-1) s(-1)) as compared to larger MFN-18. From a simple comparative study among various magnetic nanocomposites involving a MFP-18 core, the high MFN-18 r2 relaxivity value can be attributed to enhanced water diffusion and exchange due to the GO sheet, allowing better interaction between magnetic the MFP core and water protons. The proposed method can be readily extended to convert other types of hydrophobic nanoparticles into water-dispersible nanocomposites.

Magnetic resonance imaging (MRI) has become an integral part of modern clinical imaging due to its non-invasiveness and versatility in providing tissue and organ images with high spatial resolution. With the current MRI advancement, MRI imaging probes with suitable biocompatibility, good colloidal stability, enhanced relaxometric properties and advanced functionalities are highly demanded. As such, MRI contrast agents (CAs) have been an extensive research and development area. In the recent years, different inorganic-based nanoprobes comprising inorganic magnetic nanoparticles (MNPs) with an organic functional coating have been engineered to obtain a suitable contrast enhancement effect. For biomedical applications, the organic functional coating is critical to improve colloidal stability and biocompatibility. Simultaneously, it also provides a building block for generating a higher dimensional secondary structure. In this review, the combinatorial design approach by a self-assembling pre-formed hydrophobic inorganic MNPs core (from non-polar thermolysis synthesis) into various functional organic coatings (e.g. ligands, amphiphilic polymers and graphene oxide) to form water soluble nanocomposites will be discussed. The resultant magnetic ensembles were classified based on their dimensionality, namely, 0-D, 1-D, 2-D and 3-D structures. This classification provides further insight into their subsequent potential use as MRI CAs. Special attention will be dedicated towards the correlation between the spatial distribution and the associated MRI applications, which include (i) coating optimization-induced MR relaxivity enhancement, (ii) aggregation-induced MR relaxivity enhancement, (iii) off-resonance saturation imaging (ORS), (iv) magnetically-induced off-resonance imaging (ORI), (v) dual-modalities MR imaging and (vi) multifunctional nanoprobes.

This Letter describes the synthesis and biological evaluation of a number of functionalized bisimidazoles bearing annulated tricyclic motifs as potent inhibitors of HCV NS5A protein. Compound 4 h, which contains a substituted tricyclic 6-6-6 xanthene, demonstrated broad genotypic spectrum, compelling potency, and good oral bioavailability with dose-dependent drug exposure level in multiple animal species., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This Letter describes the discovery of a number of functionalized bisimidazoles bearing a cyclohexylphenyl, piperidylphenyl, or bicyclo[2,2,2]octylphenyl motif as HCV NS5A inhibitors. Compounds 2c, 4b and 6 have demonstrated low single-digit nM potency in gt-1a replicon and double-digit pM potency in gt-1b replicon, respectively. Moreover, both 4b and 6 have, respectively, exhibited good oral bioavailability in rats with a favorable liver/plasma ratio of the drug concentration., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The systemic morphologic right ventricle (RV) in congenitally corrected transposition of the great arteries or after atrial switch for transposition of the great arteries is associated with late ventricular failure. Although the role of the left ventricular assist device (LVAD) in supporting the failing LV is established, the indications and outcomes of using LVAD in a systemic RV remain unclear. We assessed the role of a third-generation LVAD for systemic RV support., Methods: Seven patients (mean age, 36 years) received the HeartWare (HeartWare International Inc, Framingham, MA) VAD for systemic RV failure (congenitally corrected transposition of the great arteries in 1 and after atrial switch in 6). Four patients (57%) had severe subpulmonic LV failure, and aggressive perioperative diuresis with or without hemofiltration was used to offload the subpulmonic LV. The indications of VAD were (1) bridge to transplant in 3 and (2) bridge to decision for a high transpulmonary gradient in 4. Transplantation outcome was compared with systemic RV failure without VAD bridge in 19 patients (years 1989 to 2013)., Results: Systemic RV support alone was achieved in all patients, with no early deaths (≤30 days). Overall, 6 (86%) returned home, 3 (44%) received a transplant, 2 (28%) died of noncardiac causes, and 2 (28%) continue on VAD support (median support, 232 days). Repeat catheterization (n = 4) showed an improved median transpulmonary gradient in 3 patients (median 18.5 mm Hg pre-VAD vs 8.0 mm Hg post-VAD). Two bridge-to-decision patients received transplants at 640 and 685 days. The stroke rate on VAD support was 43% (2 thromboembolic and 1 hemorrhagic; 3 with satisfactory recovery). De novo aortic regurgitation was 29% (n = 2; 1 valve replacement). All patients (n = 3) survived transplantation (vs 10.5% early mortality without VAD bridge; p = 1.00) and were well at follow-up (range, 53 to 700 days)., Conclusions: The third-generation VAD provides durable support for systemic RV failure as a bridge to transplant and as a strategy to reduce pulmonary vascular resistance. Although concomitant subpulmonic LV failure is common, systemic RV support alone was achieved in all patients., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: It is unclear whether novice trainees can be taught safely to perform adult cardiac surgery without any impact on early or late outcomes., Methods: All patients (n = 1305) data were obtained from an externally validated, mandatory institutional database (2003-2010). 'Novice' is defined as a trainee who required substantial assistance or supervision to perform part or whole of the specified procedure (Intercollegiate Surgical Curriculum Programme UK, Competency Level ≤2). Outcome measures were in-hospital mortality, composite score of in-hospital mortality-morbidities, mid-term survival and revascularisation rate after CABG. Follow-up up to 7 years (median 3.2 years) was determined., Results: Some 39 % (n = 510) of the cases involved novice (28 %-part, 11 %-whole procedure), 12 % (n = 157) competent trainees and 49 % (n = 638) consultant. Median EuroSCORE was higher in consultant group (p < 0.001). Without risk adjustment, composite outcome score and mid-term mortality were higher in consultant group (p = 0.03). With adjustment using EuroSCORE and propensity scores, EuroSCORE was significantly predictive of in-hospital mortality [odd ratio (OR) 1.38, 95 %CI 1.20-1.57, p < 0.001], composite outcome (OR 1.26, 95 %CI 1.15-1.37, p < 0.001) and mid-term mortality (HR 1.24, 95 %CI 1.18-1.31, p < 0.001) but not the operator categories. Further analysis of subcohort undergoing first-time, isolated CABG (n = 1070) showed that EuroSCORE remained predictive of adjusted in-hospital mortality (OR 1.39, 95 %CI 1.13-1.71, p = 0.002), composite outcome (OR 1.33, 95 %CI 1.19-1.49, p < 0.001) and mid-term mortality (HR 1.22, 95 %CI 1.10-1.35, p < 0.001). The operator categories were not associated with adjusted outcome measures including revascularisation rate after CABG., Conclusion: Supervised training in adult cardiac surgery can be achieved safely at the early learning curve phase without compromising both early and mid-term clinical outcomes.

Ectopic thyroid is a rare embryogenic anomaly that occurs during its migration from foramen caecum to its pretracheal position. An intracardiac ectopic location is even rarer and found most commonly in the right ventricular outflow tract in sporadic reports. While surgery in symptomatic patients seems appropriate, resection of non-neoplastic ectopic tissue remains a clinical equipoise. Its occurrence is often unsuspected by clinicians, but its possibility should be considered due to its typical location in the right ventricular outflow tract. Unlike true neoplastic intracardiac tumour which mandates surgical resection, both surgical and non-surgical approach may be considered for an intracardiac ectopic thyroid mass.

The essence of tissue engineering is the fabrication of autologous cells or induced stem cells in naturally derived or synthetic scaffolds to form specific tissues. Polymer is thought as an appealing source of cell-seeded scaffold owing to the diversity of its physicochemical property and can be electrospun into nano-size to mimic natural structure. Poly (L-lactic acid) (PLLA) and poly (ε-caprolactone) (PCL) are both excellent aliphatic polyester with almost "opposite" characteristics. The controlling combination of PLLA and PCL provides varying properties and makes diverse applications. Compared with the copolymers of the same components, PLLA/PCL blend demonstrates its potential in regenerative medicine as a simple, efficient and scalable alternative. In this study, we electrospun PLLA/PCL blends of different weight ratios into nanofibrous scaffolds (NFS) and their properties were detected including morphology, porosity, degradation, ATR-FTIR analysis, stress-stain assay, and inflammatory reaction. To explore the biocompatibility of the NFS we synthesized, human adipose-derived stem cells (hASCs) were used to evaluate proliferation, attachment, viability and multi-lineage differentiation. In conclusion, the electrospun PLLA/PCL blend nanofibrous scaffold with the indicated weight ratios all supported hASCs well. However, the NFS of 1/1 weight ratio showed better properties and cellular responses in all assessments, implying it a biocompatible scaffold for tissue engineering.

Rationale: Chronic obstructive pulmonary disease (COPD) guidelines make no recommendations for allergy diagnosis or treatment., Objectives: To determine whether an allergic phenotype contributes to respiratory symptoms and exacerbations in patients with COPD., Methods: Two separate cohorts were analyzed: National Health and Nutrition Survey III (NHANES III) and the COPD and domestic endotoxin (CODE) cohort. Subjects from NHANES III with COPD (n = 1,381) defined as age > 40 years, history of smoking, FEV1/FVC < 0.70, and no diagnosis of asthma were identified. The presence of an allergic phenotype (n = 296) was defined as self-reported doctor diagnosed hay fever or allergic upper respiratory symptoms. In CODE, former smokers with COPD (n = 77) were evaluated for allergic sensitization defined as a detectable specific IgE to perennial allergens. Bivariate and multivariate models were used to determine whether an allergic phenotype was associated with respiratory symptoms and exacerbations., Measurements and Main Results: In NHANES III, multivariate analysis revealed that individuals with allergic phenotype were more likely to wheeze (odds ratio [OR], 2.1; P < 0.01), to have chronic cough (OR, 1.9; P = 0.01) and chronic phlegm (OR, 1.5; P < 0.05), and to have increased risk of COPD exacerbation requiring an acute doctor visit (OR, 1.7; P = 0.04). In the CODE cohort, multivariate analysis revealed that sensitized subjects reported more wheeze (OR, 5.91; P < 0.01), more nighttime awakening due to cough (OR, 4.20; P = 0.03), increased risk of COPD exacerbations requiring treatment with antibiotics (OR, 3.79; P = 0.02), and acute health visits (OR, 11.05; P < 0.01). An increasing number of sensitizations was associated with a higher risk for adverse health outcomes., Conclusions: Among individuals with COPD, evidence of an allergic phenotype is associated with increased respiratory symptoms and risk of COPD exacerbations.

A simple and versatile synthesis method to form water soluble multifunctional nanoclusters using polyethylene glycol (PEG) functionalized poly(maleic anhydride-alt-1-octadecene) amphiphilic brush copolymers (PMAO-g-PEG) was presented. Simply by tuning the core size and the initial nanocrystal concentration, manganese ferrite nanoparticles (MFNPs) were used to demonstrate the versatility of tuning the loading amount of the nanoclusters. The resultant nanoclusters were found to have a well-controlled spherical shape. When Zn-doped AgInS2 quantum dots (AIZS QDs) were loaded together with the MFNP nanocrystals, bi-functional nanoclusters with fluorescent and magnetic behaviors were obtained. Such bi-functional nanoclusters were also successfully demonstrated for cellular bio-imaging. Moreover, the presence of another type of nanocrystals together with MFNPs was found to have a negligible effect on the overall properties of the nanoclusters as demonstrated by the MR relaxivity test. From the time-dependent colloidal stability test, it was found that the presence of the PEG chain grafted onto PMAO was able to reduce protein adsorption onto the nanocluster surface. An in vitro study on NIH/3T3 demonstrated the biocompatibility of the nanoclusters. Such biocompatible and colloidally stable nanoclusters with an approximate size of 80-120 nm were suitable for both MRI and cell labeling applications.

Carbon based 2-D material graphene oxide (GO) is a promising platform for preparing composites for biomedical applications because of its superior water solubility and low toxicity. Herein, we reported a convenient route to prepare fluorescent nanocomposites incorporating water-soluble GO sheets and Zn doped AgInS 2 nanoparticles. According to the study, the photoluminescence of the Zn doped AgInS 2 nanoparticles was well maintained after the hybridization using GO. No obvious emission shift was observed and the PL intensity was stable for over three months with negligible quenching. The PEGylated AIZS-GO nanocomposites could be readily up-taken by NIH/3T3 cells (mouse embryonic fibroblast cell line) while no distinct cytotoxicity was observed. The subsequent in vitro cellular imaging of NIH/3T3 cells proved that the as-prepared AIZS-GO-PEG nanocomposites were potential fluorescent probes for biomedical targeting and imaging.

In this study, MnFe(2)O(4) nanoparticle (MFNP)-decorated graphene oxide nanocomposites (MGONCs) are prepared through a simple mini-emulsion and solvent evaporation process. It is demonstrated that the loading of magnetic nanocrystals can be tuned by varying the ratio of graphene oxide/magnetic nanoparticles. On top of that, the hydrodynamic size range of the obtained nanocomposites can be optimized by varying the sonication time during the emulsion process. By fine-tuning the sonication time, MGONCs as small as 56.8 ± 1.1 nm, 55.0 ± 0.6 nm and 56.2 ± 0.4 nm loaded with 6 nm, 11 nm, and 14 nm MFNPs, respectively, are successfully fabricated. In order to improve the colloidal stability of MGONCs in physiological solutions (e.g., phosphate buffered saline or PBS solution), MGONCs are further conjugated with polyethylene glycol (PEG). Heating by exposing MGONCs samples to an alternating magnetic field (AMF) show that the obtained nanocomposites are efficient hyperthermia agents. At concentrations as low as 0.1 mg Fe mL(-1) and under an 59.99 kA m(-1) field, the highest specific absorption rate (SAR) recorded is 1588.83 W g(-1) for MGONCs loaded with 14 nm MFNPs. It is also demonstrated that MGONCs are promising as magnetic resonance imaging (MRI) T(2) contrast agents. A T(2) relaxivity value (r(2) ) as high as 256.2 (mM Fe)(-1) s(-1) could be achieved with MGONCs loaded with 14 nm MFNPs. The cytotoxicity results show that PEGylated MGONCs exhibit an excellent biocompatibility that is suitable for biomedical applications., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Polycrystalline graphene grown by chemical vapor deposition (CVD) on metals and transferred onto arbitrary substrates has line defects and disruptions such as wrinkles, ripples, and folding that adversely affect graphene transport properties through the scattering of the charge carriers. It is found that graphene assembled with metal nanowires (NWs) dramatically decreases the resistance of graphene films. Graphene/NW films with a sheet resistance comparable to that of the intrinsic resistance of graphene have been obtained and tested as a transparent electrode replacing indium tin oxide films in electrochromic (EC) devices. The successful integration of such graphene/NW films into EC devices demonstrates their potential for a wide range of optoelectronic device applications.

We report the successful use of MitroFast® annuloplasty ring in the setting of active endocarditis to preserve the native valve mechanism despite complete posterior leaflet destruction. This patient remained well at 20 month follow-up after her surgery.

Tissue engineering is clinically promising for missing and damaged tissues. Adipose-derived stem cells (ASCs), a type of mesenchymal stem cells, represent a reliable source of seed cells for tissue engineering with multiple merits such as minimal invasion, abundant yield, little immunity, low morbidity, easy isolation, and rapid expansion. However, because the properties of adipose tissue-derived cells differ depending on the fat depot from which they are derived, we compared the ASCs from three anatomic sites of New Zealand white rabbits: subcutaneous inguinal (SI), subcutaneous dorsocervical (SD), and retroperitoneal perinephric (RP) regions. We investigated cellular behaviors including proliferation, viability, and differentiation. The ASCs of the subcutaneous regions (SI and SD) had higher performances in all assessments compared to those of the RP region. Moreover, the SI and SD ASCs had significant differences, with SI ASCs having better properties than SD ASCs. We conclude that the different anatomic distributions of fat contribute to the different behaviors of ASCs. The SI region offers the most applicable cell source reservoir for ASC tissue engineering., (Copyright © 2011 S. Karger AG, Basel.)

Immunotherapy which has been in practice for more than 20 years proves effective for the treatment of metastatic renal cell carcinoma (mRCC). Anti-angiogenesis-targeted therapy has recently been identified as a promising therapeutic strategy for mRCC. This study was aimed to evaluate the effectiveness of vascular endothelial growth factor (VEGF) pathway-targeted therapy for mRCC by comparing its effectiveness with that of immunotherapy. The electronic databases were searched. Randomized controlled trials (RCTs) on comparison of VEGF inhibiting drugs (sorafenib, sunitinib and bevacizumab) with interferon (IFN) or placebo for mRCC treatment were included. Data were pooled to meta-analyze. A total of 7 RCTs with 3451 patients were involved. The results showed that anti-VEGF agents improved progression-free survival (PFS) and offered substantial clinical benefits to patients with mRCC. Among them, sunitinib had a higher overall response rate (ORR) than IFN (47% versus 12%, P<0.000001). Bevacizumab plus IFN produced a superior PFS [risk ratio (RR): 0.86, 95% confidence interval (CI): 0.76-0.97; P=0.01] and ORR (RR: 2.19; 95% CI: 1.72-2.78; P<0.00001) in patients with mRCC over IFN, but it yielded an increase by 31% in the risk of serious toxic effects (RR: 1.31; 95% CI: 1.20-1.43; P<0.00001) as compared with IFN. The overall survival (OS) was extended by sorafenib (17.8 months) and sunitinib (26.4 months) as compared with IFN (13 months). It was concluded that compared with IFN therapy, VEGF pathway-targeted therapies improved PFS and achieved significant therapeutic benefits in mRCC. However, the risk to benefit ratio of these agents needs to be further evaluated.

In a randomised trial, we compared the effects of oral sildenafil (0.5 mg.kg(-1) ) and placebo, administered the day before cardiac surgery, in 24 children. In sildenafil vs placebo patients, pre-cardiopulmonary bypass median (IQR [range]) cyclic-guanosine-monophosphate was not significantly different (29.9 (2.1-208.1 [0.5-391.5]) vs 5.2 (0.3-54.6 [0-628.9]) pmol.ml(-1) , respectively). Post-cardiopulmonary bypass, nitrate/nitrite levels were also not significantly different (0.7 (0-8.0 [0-142.8]) vs 0 (0-2.7 [0-52.7]) μM, respectively). Postoperatively, mean (SD) pulmonary vascular resistance (2.64 (2.28) vs 1.90 (1.12) WU.m(-2) , respectively and oxygenation index (5.29 (4.60) vs 3.38 (2.54), respectively) remained unchanged, whilst oxygen delivery (57.18 (21.24) vs 74.13 (35.46) ml.min(-1) .m(-2) , respectively) and bi-ventricular systolic function (left ventricle 3.78 (0.94) vs 4.55 (1.08) cm.s(-1) , respectively; p=0.002; right ventricle 6.93 (1.47) vs 8.09 (2.25) cm.s(-1) , respectively; p<0.001) were significantly reduced in the sildenafil group. In this trial, pre-operative sildenafil did not affect postoperative pulmonary vascular resistance. There was, however, a negative impact on ventricular function and oxygenation., (© 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.)

Objective: To compare the myogenic differentiation ability in vitro of rabbit adipose-derived stem cells (ADCSs) from different sites so as to provide ideal seed cells for repair and reconstruction of urinary tract., Methods: Adipose tissues were obtained from the nape of the neck, post peritoneum, and vicinity of epididymis of a 4-month-old male New Zealand rabbit and ADSCs were harvested through collagenase digestion. ADSCs were purified by differential attachment method. The protein marker CD44 of rabbit ADSCs was used to identify the stem cells by immunocytochemistry, then the 5th generation of ADSCs were induced to differentiate into adipogenic, osteogenic, and myogenic cells. Multi-differentiation was confirmed by Oil red O staining, von Kossa staining, and RT-PCR. Myogenic differentiation abilities of ADSCs from 3 different sites were compared between the control group (L-DMEM medium containing 10%FBS) and the experimental group (myogenic medium) by RT-PCR method., Results: ADSCs could be easily isolated from adipose tissues of the nape of the neck, post peritoneum, and vicinity of epididymis. ADSCs displayed a typical cobblestone morphology. Brown particles could be seen in ADSCs by CD44 immunocytochemistry staining. Oil red O staining showed red fat drops in ADSCs after 14 days of adipogenic culture. Black matrix could be seen in ADSCs by von Kossa staining after 28 days of osteogenic culture. RT-PCR detection showed moderate alpha-actin expression in the control group and strong alpha-actin expression in the experimental group after 42 days of myogenic culture. The growth rate of alpha-actin from the adipose tissue of post peritoneum (28.622% +/- 4.879%) was significantly lower (P < 0.05) than those from the adipose tissues of the nape of the neck (35.471% +/- 3.434%) and vicinity of epididymis (38.446% +/- 4.852%)., Conclusion: The ADSCs from different sites show different myogenic differentiation abilities in vitro. ADSCs from the adipose tissues of the nape of the neck and vicinity of epididymis can be used as ideal seed cells for tissue engineering of lower urinary tract.

Numerous studies have shown that mammalian target of rapamycin (mTOR) inhibitor activates Akt signaling pathway via a negative feedback loop while inhibiting mTORC1 signaling. In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin-mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors. Moreover, we analyzed the effect of mTORC1 and mTORC2 on regulating cell cycle progression. We found that low concentrations rapamycin increased Akt and ERK phosphorylation through a mTORC1-dependent mechanism because knockdowned raptor induced the activation of Akt and ERK, but higher doses of rapamycin inhibited Akt and ERK phosphorylation mainly via the mTORC2 signaling pathway because that the silencing of rictor led to the inhibition of Akt and ERK phosphorylation. We further showed that mTORC2 was tightly associated with the development of cell cycle through an Akt-dependent mechanism. Therefore, we combined PI3K and ERK inhibitors prevent rapamycin-induced Akt activation and enhanced antitumor effects of rapamycin. Collectively, we conclude that mTORC2 plays a much more important role than mTORC1 in rapamycin-mediated phosphorylation of Akt and ERK, and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin-based therapeutic approaches in cancer cells., ((c) 2010 Wiley-Liss, Inc.)

Objective: The national guideline recommends selective case finding as the main strategy by identification of high risk people. This study assessed whether high risk patients were identified before their presentation with fragility fracture., Methods: A prospective study for 3.5 consecutive months on patients with low energy hip fractures to Brighton and Sussex University Hospital NHS Trusts, which serves a population of 460,000. Data were collected by interview using standardised form, medical record review, and communication with family physicians. Definition of high risk: (1) untreated hypogonadism (2) corticosteroid users (3) disorders with increased bone loss (4) previous fragility fractures., Results: 98 patients were admitted with hip fracture. Thirty nine (40%) had at least one high risk factor. High risk patients (7 of 39, 18%) were no more likely to receive prophylaxis compared with patients without high risk factor (5 of 59, 8%) (p = 0.21). Previous fragility fracture (23) was the commonest risk factor followed by disorders with increased bone loss (10), premature menopause (10), and corticosteroid users (5). Fifteen patients (15%) had susceptibility to frequent falls and two had maternal history of osteoporosis. The proportion of treated patients were 20% (2 of 10) in premature menopause, 10% (1 of 10) in diseases with secondary osteoporosis, 13% (3 of 23) in previous fragility fracture, and 80% (4 of 5) in corticosteroid users (p = 0.01), Conclusion: Prevention of hip fracture is still inadequate in high risk patients. Discrepancy seemed to exist in treatment frequency among different high risk groups suggesting that emphasis on prevention of osteoporosis has not been reinforced in all people at risk.

Tectal plate cysts are very rare. We report two adult patients with benign tectal plate cyst and secondary hydrocephalus. The first patient had an unusual eye movement disorder with bilateral upper eyelid retraction (Collier's sign), limited upgaze, severe upgaze evoked nystagmus and retraction nystagmus. The second patient presented with ataxia and failure of upward gaze. Endoscopic fenestration of the tectal plate cyst and endoscopic third ventriculostomy in both cases result in neurological improvement. To the best of our knowledge, similar lesions at this site have not been reported in adults. The differential diagnosis with arachnoid cysts of the quadrigeminal CSF cistern is discussed.

A precolumn derivatization liquid chromatography (LC) method was developed for the analysis of various dietary supplement formulations and raw materials for glucosamine. A 1 mL sample or standard water solution (containing about 0.05 mg glucosamine) was mixed with 1 mL pH 8.3 buffer, 1 mL 5% phenylisothiocyanate methanolic solution, and derivatized at 80 degrees C in a water bath for 30 min. After derivatization, the solution was cooled in a cold water bath and centrifuged at 3000-5000 rpm. The clear upper layer was ready for injection. The LC system was equipped with a C18 reversed-phase column and an ultraviolet detector set at 240 nm. The column was developed with a linear gradient composed of 0.1% phosphoric acid in deionized water and 0.1% phosphoric acid in methanol. The method was subjected to Single Laboratory Validation. The method precision was 0.50% relative standard deviation, accuracy was less than +/-1.5%, method linearity in the range 0-2 mg glucosamine/mL was 1.00, the detection limit was 0.0705 microg/mL, and the quantitation limit was 0.235 microg/mL. Chondroitin sulfate, amino acids, and excipients did not interfere with glucosamine testing. After derivatization, both standard and sample preparations were stable for at least 48 h. Due to its high sensitivity, this method can be used to assay glucosamine in functional foods and pet foods. The validation data will be published separately.

Microsatellite instability is present in over 80% of the hereditary non-polyposis colorectal carcinoma and about 15-20% of the sporadic cancer. Microsatellite instability is caused by the inactivation of the mismatch repair genes, such as primarily hMLH1, hMSH2. To study the mechanisms of the inactivation of mismatch repair genes in colorectal cancers, especially the region-specific methylation of hMLH1 promoter and its correlation with gene expression, we analysed microsatellite instability, expression and methylation of hMLH1 and loss of heterozygosity at hMLH1 locus in these samples. Microsatellite instability was present in 17 of 71 primary tumours of colorectal cancer, including 14 of 39 (36%) mucinous cancer and three of 32 (9%) non-mucinous cancer. Loss of hMLH1 and hMSH2 expression was detected in nine and three of 16 microsatellite instability tumours respectively. Methylation at CpG sites in a proximal region of hMLH1 promoter was detected in seven of nine tumours that showed no hMLH1 expression, while no methylation was present in normal mucosa and tumours which express hMLH1. However, methylation in the distal region was observed in all tissues including normal mucosa and hMLH1 expressing tumours. This observation indicates that methylation of hMLH1 promoter plays an important role in microsatellite instability with a region-specific manner in colorectal cancer. Loss of heterozygosity at hMLH1 locus was present in four of 17 cell lines and 16 of 54 tumours with normal hMLH1 status, while loss of heterozygosity was absent in all nine cell lines and nine tumours with abnormal hMLH1 status (mutation or loss of expression), showing loss of heterozygosity is not frequently involved in the inactivation of hMLH1 gene in sporadic colorectal cancer.

We report the discovery of three cool brown dwarfs that fall in the effective temperature gap between the latest L dwarfs currently known, with no methane absorption bands in the 1-2.5 µm range, and the previously known methane (T) dwarfs, whose spectra are dominated by methane and water. The newly discovered objects were detected as very red objects in the Sloan Digital Sky Survey imaging data and have JHK colors between the red L dwarfs and the blue Gl 229B-like T dwarfs. They show both CO and CH(4) absorption in their near-infrared spectra in addition to H(2)O, with weaker CH(4) absorption features in the H and K bands than those in all other methane dwarfs reported to date. Due to the presence of CH(4) in these bands, we propose that these objects are early T dwarfs. The three form part of the brown dwarf spectral sequence and fill in the large gap in the overall spectral sequence from the hottest main-sequence stars to the coolest methane dwarfs currently known.

We describe the lasing characteristics of an external-cavity 1.3-microm-wavelength traveling-wave semiconductor laser that uses a tilted-stripe optical amplifier. It was found that within a 45-nm-wavelength tuning range the power level does not suffer any discontinuous change. The lasing spectrum remains single mode within a 35-nm range, and the linewidth is less than 50 kHz. The lasing frequency is stable and changes by only 25 MHz/ degrees C and by approximately 1.6 MHz/mA. For cw operation the intracavity power reaches 24 mW, and for long-pulse operation the power level is as high as 175 mW. The lasing power level exhibits long-term stability. Moreover the intracavity power level is found to be insensitive to the coupled output power.