Temporal dynamics of lactate concentration in the human brain during acute inspiratory hypoxia.

Purpose: To demonstrate the feasibility of measuring the temporal dynamics of cerebral lactate concentration and examine these dynamics in human subjects using magnetic resonance spectroscopy (MRS) during hypoxia.

Materials And Methods: A respiratory protocol consisting of 10-minute baseline normoxia, 20-minute inspiratory hypoxia, and ending with 10-minute normoxic recovery was used, throughout which lactate-edited MRS was performed. This was repeated four times in three subjects.

Nanotwinning and structural phase transition in CdS quantum dots.

Nanotwin structures are observed in high-resolution transmission electron microscopy studies of cubic phase CdS quantum dots in powder form by chemical co-precipitation method. The deposition of thin films of nanocrystalline CdS is carried out on silicon, glass, and TEM grids keeping the substrates at room temperature (RT) and 200°C by pulsed laser ablation. These films are then subjected to thermal annealing at different temperatures.

Opto-structural studies of well-dispersed silicon nano-crystals grown by atom beam sputtering.

Synthesis and characterization of nano-crystalline silicon grown by atom beam sputtering technique are reported. Rapid thermal annealing of the deposited films is carried out in Ar + 5% H2 atmosphere for 5 min at different temperatures for precipitation of silicon nano-crystals. The samples are characterized for their optical and structural properties using various techniques.

Does the axillary lymph node ratio have any added prognostic value over pN staging for South East Asian breast cancer patients?

Introduction: Lymph node ratio (LNR, i.e. the ratio of the number of positive nodes to the total number of nodes excised) is reported to be superior to the absolute number of nodes involved (pN stage) in classifying patients at high versus low risk of death following breast cancer.

Differential activities of the two closely related withanolides, Withaferin A and Withanone: bioinformatics and experimental evidences.

Background And Purpose: Withanolides are naturally occurring chemical compounds. They are secondary metabolites produced via oxidation of steroids and structurally consist of a steroid-backbone bound to a lactone or its derivatives. They are known to protect plants against herbivores and have medicinal value including anti-inflammation, anti-cancer, adaptogenic and anti-oxidant effects.

Breast cancer in South East Asia: comparison of presentation and outcome between a middle income and a high income country.

Background: There are large differences in socio-economic growth within the region of South East Asia, leading to sharp contrasts in health-systems development between countries. This study compares breast cancer presentation and outcome between patients from a high income country (Singapore) and a middle income country (Malaysia) in South East Asia.

Methods: Within the Singapore Malaysia Breast Cancer Registry we identified all consecutive patients diagnosed with breast cancer between 1993 and 2007 at the National University Hospital in Singapore (high income country, n=2,141) and the University of Malaya Medical Center in Kuala Lumpur, Malaysia (middle income country, n=3,320).

Identification and structural elucidation of two process impurities and stress degradants in darifenacin hydrobromide active pharmaceutical ingredient by LC-ESI/MS(n).

The present study describes the identification and characterization of two process impurities and major stress degradants in darifenacin hydrobromide using high performance liquid chromatography (HPLC) analysis. Forced degradation studies confirmed that the drug substance was stable under acidic, alkaline, aqueous hydrolysis, thermal and photolytic conditions and susceptible only to oxidative degradation. Impurities were identified using liquid chromatography coupled with ion trap mass spectrometry (LC-MS/MS(n)).

Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis.

A number of factors have been identified that increase the risk of hepatocellular carcinoma (HCC). Recently it has become appreciated that type II diabetes increases the risk of developing HCC. This represents a patient population that can be identified and targeted for cancer prevention.

Comparison of aprotinin and tranexamic acid in adult scoliosis correction surgery.

Purpose: A retrospective review of consecutive adult patients undergoing scoliosis correction surgery was performed to compare the effects of aprotinin and tranexamic acid in blood conservation and to define a comprehensive blood conservation strategy for such surgery.

Methods: Medical records of all patients who underwent scoliosis correction surgery in this unit between January 2003 and December 2008 were reviewed. The patients were divided into three cohorts: group 1 receiving no antifibrinolytics, group 2 aprotinin and group 3 tranexamic acid.

Adjuvant! Online is overoptimistic in predicting survival of Asian breast cancer patients.

Background: Adjuvant! Online is a free web-based tool which predicts 10-year breast cancer outcomes and the efficacy of adjuvant therapy in patients with breast cancer. As its prognostic performance has only been validated in high income Caucasian populations, we validated the model in a middle income Asian setting.

Methods: Within the University Malaya Hospital-Based Breast Cancer Registry, all 631 women who were surgically treated for invasive non-metastatic breast cancer between 1993 and 2000 were identified.

Ethnic differences in survival after breast cancer in South East Asia.

Background: The burden of breast cancer in Asia is escalating. We evaluated the impact of ethnicity on survival after breast cancer in the multi-ethnic region of South East Asia.

Methodology/principal Findings: Using the Singapore-Malaysia hospital-based breast cancer registry, we analyzed the association between ethnicity and mortality following breast cancer in 5,264 patients diagnosed between 1990 and 2007 (Chinese: 71.

Honokiol activates AMP-activated protein kinase in breast cancer cells via an LKB1-dependent pathway and inhibits breast carcinogenesis.

Introduction: Honokiol, a small-molecule polyphenol isolated from magnolia species, is widely known for its therapeutic potential as an antiinflammatory, antithrombosis, and antioxidant agent, and more recently, for its protective function in the pathogenesis of carcinogenesis. In the present study, we sought to examine the effectiveness of honokiol in inhibiting migration and invasion of breast cancer cells and to elucidate the underlying molecular mechanisms.

Methods: Clonogenicity and three-dimensional colony-formation assays were used to examine breast cancer cell growth with honokiol treatment.

Med1 plays a critical role in the development of tamoxifen resistance.

Understanding the molecular pathways that contribute to the development of tamoxifen resistance is a critical research priority as acquired tamoxifen resistance is the principal cause of poor prognosis and death of patients with originally good prognosis hormone-responsive breast tumors. In this report, we provide evidence that Med1, an important subunit of mediator coactivator complex, is spontaneously upregulated during acquired tamoxifen-resistance development potentiating agonist activities of tamoxifen. Phosphorylated Med1 and estrogen receptor (ER) are abundant in tamoxifen-resistant breast cancer cells due to persistent activation of extracellular signal-regulated kinases.

Hysteroscopic metroplasty in women with primary infertility and septate uterus: reproductive performance after surgery.

Objective: To assess reproductive performance in women with septate uterus and otherwise unexplained infertility after hysteroscopic metroplasty.

Study Design: A total of 72 women with septate uterus and otherwise unexplained primary infertility were included in the study. All of the women underwent hysteroscopic septal resection.

Lumbar peritoneal shunt in idiopathic intracranial hypertension.

Aim: Treatment options for idiopathic intracranial hypertension (IIH) are lumbar peritoneal shunt (LP), optic nerve fenestration, ventriculoperitoneal shunt and venous stenting. We report our experience of 24 cases of LP shunt. MATERIAL and

Methods: All the patients had preoperative fundus examination, cerebrospinal fluid pressure estimation and examination, visual field charting, CT scan and MR venography.

Leptin-induced epithelial-mesenchymal transition in breast cancer cells requires β-catenin activation via Akt/GSK3- and MTA1/Wnt1 protein-dependent pathways.

Perturbations in the adipocytokine profile, especially higher levels of leptin, are a major cause of breast tumor progression and metastasis; the underlying mechanisms, however, are not well understood. In particular, it remains elusive whether leptin is involved in epithelial-mesenchymal transition (EMT). Here, we provide molecular evidence that leptin induces breast cancer cells to undergo a transition from epithelial to spindle-like mesenchymal morphology.

Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells.

Background: Scopolamine is a well-known cholinergic antagonist that causes amnesia in human and animal models. Scopolamine-induced amnesia in rodent models has been widely used to understand the molecular, biochemical, behavioral changes, and to delineate therapeutic targets of memory impairment. Although this has been linked to the decrease in central cholinergic neuronal activity following the blockade of muscarinic receptors, the underlying molecular and cellular mechanism(s) particularly the effect on neuroplasticity remains elusive.

Glp-1 analog, liraglutide, ameliorates hepatic steatosis and cardiac hypertrophy in C57BL/6J mice fed a Western diet.

The aims of this study were designed to determine whether liraglutide, a long-acting glucagon-like peptide, could reverse the adverse effects of a diet high in fat that also contained trans-fat and high-fructose corn syrup (ALIOS diet). Specifically, we examined whether treatment with liraglutide could reduce hepatic insulin resistance and steatosis as well as improve cardiac function. Male C57BL/6J mice were pair fed or fed ad libitum either standard chow or the ALIOS diet.

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells.

Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells.

Role of mitogen activated protein kinases in skin tumorigenicity of patulin.

WHO has highlighted the need to evaluate dermal toxicity of mycotoxins including Patulin (PAT), detected in several fruits. In this study the skin carcinogenic potential of topically applied PAT was investigated. Single topical application of PAT (400 nmol) showed enhanced cell proliferation (~2 fold), along with increased generation of ROS and activation of ERK, p38 and JNK MAPKs, in mouse skin.

GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy.

Background: Nonalcoholic fatty liver disease (NAFLD) is a known outcome of hepatosteatosis. Free fatty acids (FFA) induce the unfolded protein response (UPR) or endoplasmic reticulum (ER) stress that may induce apoptosis. Recent data indicate ER stress to be a major player in the progression of fatty liver to more aggressive lesions.

Effect of acetaminophen on international normalized ratio in patients receiving warfarin therapy.

Warfarin is known to have extensive interactions with many classes of drugs. The literature suggesting a relevant interaction between acetaminophen and warfarin is inconsistent. Considering the ubiquitous use of acetaminophen, a review of the effects on international normalized ratio (INR) in patients taking warfarin was necessary.

Adiponectin inhibits leptin signalling via multiple mechanisms to exert protective effects against hepatic fibrosis.

Adiponectin is protective against hepatic fibrosis, whereas leptin promotes fibrosis. In HSCs (hepatic stellate cells), leptin signals via a JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) pathway, producing effects that enhance ECM (extracellular matrix) deposition. SOCS-3 (suppressor of cytokine signalling-3) and PTP1B (protein tyrosine phosphatase 1B) are both negative regulators of JAK/STAT signalling, and recent studies have demonstrated a role for adiponectin in regulating SOCS-3 expression.

Engineering articular cartilage with spatially-varying matrix composition and mechanical properties from a single stem cell population using a multi-layered hydrogel.

Despite significant advances in stem cell differentiation and tissue engineering, directing progenitor cells into three-dimensionally (3D) organized, native-like complex structures with spatially-varying mechanical properties and extra-cellular matrix (ECM) composition has not yet been achieved. The key innovations needed to achieve this would involve methods for directing a single stem cell population into multiple, spatially distinct phenotypes or lineages within a 3D scaffold structure. We have previously shown that specific combinations of natural and synthetic biomaterials can direct marrow-derived stem cells (MSC) into varying phenotypes of chondrocytes that resemble cells from the superficial, transitional, and deep zones of articular cartilage.