Sequential differentiation of mesenchymal stem cells in an agarose scaffold promotes a physis‐like zonal alignment of chondrocytes

Chondrocytes of the epiphyseal growth plate (physis) differentiate and mature in defined linear zones. The current study examines the differentiation of human bone marrow derived mesenchymal stem cells (hBMSCs) into zonal physeal cartilage. hBMSCs were embedded in an agarose scaffold with only the surface of the scaffold in direct contact with the culture medium. The cells were differentiated using a two‐step system involving the sequential addition of TGFβ followed by BMP2. The resultant samples displayed a heterogenic population of physis‐like collagen type 2 positive cells including proliferating chondrocytes and mature chondrocytes showing hypertrophy, expression of early bone markers and matrix mineralization. Histological analysis revealed a physis‐like linear zonal alignment of chondrocytes in varying stages of differentiation. The less mature chondrocytes were seen at the base of the construct while hypertrophic chondrocytes and matrix mineralization was observed closer to the surface of the construct. The described differentiation protocol using hBMSCs in an agarose scaffold can be used to study the factors and conditions that influence the differentiation, proliferation, maturation, and zonal alignment of physeal chondrocytes. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1753–1759, 2012     

Hypnotizability and the use of traditional dhami-jhankri healing in nepal

This study examined the role of hypnotic responsiveness in the practice of a dhami-jhankri, a traditional Nepali healer. The hypnotic capacity of 248 male patients was measured in an allopathic (Western) clinic, an Ayurvedic (ancient Hindu healing art) clinic, and a dhami-jhankri's practice. Hypnotizability was assessed using the Hypnotic Induction Profile (HIP). The Induction scores of the HIP were significantly higher among the dhami-jhankri's patients than among either the Ayurvedic or allopathic patients. Furthermore, patients who returned to the dhami-jhankri were more highly hypnotizable than first-time dhami-jhankri patients. In addition, treatment satisfaction as reported by dhami-jhankri patients was positively correlated with HIP scores. The authors conclude that hypnotic phenomena as measured in the West might be an important component of the dhami-jhankri's treatment in the East.     

First transcatheter aortic valve implantation for severe pure aortic regurgitation in Asia

Transcatheter aortic valve implantation (TAVI) has become the standard of care for inoperable patients with symptomatic severe aortic stenosis (AS), and an alternative to open aortic valve replacement for patients at high surgical risk. TAVI has also been performed in several groups of patients with off-label indications such as severe bicuspid AS, and as a valve-in-valve therapy for a degenerated surgical bioprosthesis. Although TAVI with CoreValve® prosthesis is technically challenging, and global experience in the procedure is limited, the procedure could be a treatment option for well-selected patients with severe pure aortic regurgitation (AR). Herein, we report Asia''s first case of TAVI for severe pure AR in a patient who was at extreme surgical risk, with good clinical outcome at six months.     

The bicalutamide Early Prostate Cancer Program. Demography

BACKGROUND: The optimal treatment for early prostate cancer has yet to be established. A well-tolerated hormonal therapy such as bicalutamide could be a useful treatment option in this setting, either as adjuvant or immediate therapy. A major collaborative clinical trials program was set up to investigate bicalutamide as a treatment option for local prostate cancer (localized or locally advanced disease). METHODS: The bicalutamide Early Prostate Cancer program comprises three randomized, double-blind, placebo-controlled trials of similar design that are being conducted in distinct geographical areas (North America; Australia, Europe, Israel, South Africa and Mexico; and Scandinavia). Men with T1b-4N0-1M0 (TNM 1997) prostate cancer have been randomized on a 1:1 basis to receive bicalutamide 150 mg daily or placebo. Recruitment to the program closed in July 1998, and follow-up is ongoing. Study endpoints include time to clinical progression, overall survival and tolerability. RESULTS: 8113 men aged 38 to 93 years (mean 66.9) were randomized over a 3-year period. 67.4% of the enrolled patients had localized disease (T1-2) and 66.4% had a Gleason score 相似文献   

Selective formation of pyridinic-type nitrogen-doped graphene and its application in lithium-ion battery anodes

We report a high-yield single-step method for synthesizing nitrogen-doped graphene nanostripes (N-GNSPs) with an unprecedentedly high percentage of pyridinic-type doping (>86% of the nitrogen sites), and investigate the performance of the resulting N-GNSPs as a lithium-ion battery (LIB) anode material. The as-grown N-GNSPs are compared with undoped GNSPs using scanning electron microscopy (SEM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), helium ion-beam microscopy (HIM), and electrochemical methods. As an anode material we find that pyridinic-type N-GNSPs perform similarly to undoped GNSPs, suggesting that pyridinic sites alone are not responsible for the enhanced performance of nitrogen-doped graphene observed in previous studies, which contradicts common conjectures. In addition, post-mortem XPS measurements of nitrogen-doped graphene cycled as a lithium-ion battery anode are conducted for the first time, which reveal direct evidence for irreversible chemical changes at the nitrogen sites during cycling. These findings therefore provide new insights into the mechanistic models of doped graphene as LIB anodes, which are important in improving the anode designs for better LIB performance.

Selectively pyridinic type nitrogen-doped graphene is fabricated and applied as a lithium ion battery anode including post mortem characterization.     

Pharmacokinetics and Tissue Distribution of Pilocarpine After Application to Eyelid Skin of Rats

Extending the delivery of drugs into the eyes while reducing systemic bioavailability is of utmost importance in the management of chronic ocular diseases. Topical application onto the lower eyelid skin, as an alternative to eye drops, is seen to be a valuable strategy in the treatment of chronic eye diseases. To elucidate the critical value of delivering drugs in solution onto the eyeball through the eyelid skin, pharmacokinetic studies of pilocarpine were conducted, and the results were verified using a direct pharmacodynamic study in rats. The mean residence time of pilocarpine after topical eyelid application to the eyelid skin, conjunctiva, eyeball, and plasma were 14.9, 8.50, 6.29, and 8.11 h, respectively. Conjunctiva and eyeball concentrations of pilocarpine at 8 h were 80-fold and 8-fold higher after topical eyelid application, respectively, than those for eye drops. Pupillary constriction was sustained over 8 h after topical eyelid application. Topical eyelid skin application exhibited a localized drug absorption and specific drug accumulation in the ocular tissues. Hence, it is rational to prepare topical formulations directed onto the eyelid skin, which is suitable for drugs required for long-term treatment.     

Striatal Dopamine Transporter Availability in Drug-Naive Patients With Schizophrenia: A Case-Control SPECT Study With [99mTc]-TRODAT-1 and a Meta-Analysis

Central dopaminergic hyperactivity has been one of the main hypotheses of the pathophysiology of schizophrenia since the 1970s. Excess dopamine (DA) neurotransmission in the striatum is hypothesized to alter the processing of information and result in psychotic symptoms in schizophrenia. Single photon emission computerized tomography (SPECT) provides in vivo indices of DA neurotransmission. Our study aimed to compare dopamine transporter (DAT) availability between drug-naive patients with schizophrenia and controls using SPECT. DAT availability through [^99mTc]-TRODAT-1 SPECT was compared between 47 drug-naive patients with recent-onset schizophrenia and 112 healthy controls. We also conducted a random-effects meta-analysis of the available literature synthesizing the results of 6 comparable published articles as well as our current data. The mean specific striatal binding showed a statistical trend for a reduction among the patients compared with controls (estimated difference = 0.071; 95% CI −0.01, 0.15; P = .08). There was an effect of gender, whereby females had a higher ratio of specific striatal binding than males. Age was negatively correlated with the ratio of specific striatal binding, both in patients and controls. The meta-analysis provided a pooled standardized effect size (Cohen’s d) of −0.07 (95% CI −0.31, 0.18; P = .60) for the patient vs control comparison in TRODAT binding, with no evidence of heterogeneity between studies or publication bias. Our findings suggest that striatal DAT levels are not altered in the early stages of schizophrenia before medication is introduced. We identified gender differences and aging effects that could have significance for future studies.