Cancer-associated fibroblasts (CAFs) secrete various pro-tumorigenic cytokines, yet the role of these cytokines in the progression of endometrial cancer remains unclear. We found that CAFs isolated from human endometrial cancer (EC) tissues secreted high levels of interleukin-6 (IL-6), which promotes EC cell proliferation in vitro. Neutralizing IL-6 in CAF-conditioned media reduced (47% inhibition) while IL-6 recombinant protein increased cell proliferation (~2.4 fold) of both EC cell lines and primary cultures. IL-6 receptors (IL-6R and gp130) were expressed only in EC epithelial cells but not in CAF, indicating a one-way paracrine signaling. In the presence of CAF-conditioned media, Janus kinase/signal transducers and activators of transcription (JAK/STAT3) pathway was activated in EC cells. Treatment with JAK and STAT3 specific inhibitors, AD412 and STATTIC, respectively, significantly abrogated CAF-mediated cell proliferation, indicating the role of IL-6 activation in EC cell proliferation. We further showed that one of STAT-3 target genes, c-Myc, was highly induced in EC cells after exposure to CAF-conditioned medium at both mRNA (>105-fold vs. control) and protein level (>2-fold vs. control). EC cell proliferation was dependent on c-Myc expression, as RNAi-mediated c-Myc down-regulation led to a significant 46% reduction in cell viability when compared with scrambled control. Interestingly, CAF-conditioned media failed to promote proliferation in EC cells with reduced c-Myc expression, suggesting that CAF-mediated cell proliferation was also dependent on c-Myc expression. Subcutaneous tumor xenograft model showed that EC cells grew at least 1.4 times larger when co-injected with CAF, when compared to those injected with EC cells alone. Mice injected with EC cells with down-regulated c-Myc expression, however, showed at least 2.5 times smaller tumor compared to those in control group. Notably, there was no increase of tumor size when co-injected with CAFs. Further immunohistochemical staining on human tissues showed positive expression of IL-6 receptors, phosphorylated-STAT3 and c-Myc in human EC tissues with less signals in benign endometrium. Taken together, our data suggests that IL-6 secreted by CAF induces c-Myc expression to promote EC proliferation in vitro and in vivo. IL-6 pathway can be a potential target to disrupt tumor-stroma interaction in endometrial cancer progression.
Purpose: The aim of this paper is to demonstrate fundamental photographic techniques and standardized views in oculoplastic disease and surgery outside of a photographic studio.
Methods: A Canon EOS 60D digital single lens reflex (DSLR) camera, which was fitted with a Canon EF-S 60 mm USM macro lens, was used to photograph the subject. A Canon MR-14EX Macro Ringlite was used to illuminate the subject. Informed written consent was obtained for publication of the photographs used in this study. The photographs were taken in an ophthalmology clinic using standardized photographic settings at various magnification ratios. The magnification ratios were recalibrated and adjusted to accommodate the smaller sensor size in-line with standardized medical photography guidelines.
Results: We present a series of core views for various oculoplastic and orbital disease presentations.
Conclusions: It is possible to capture quality standardized digital photographs in a busy clinical environment without the need for a dedicated photographic studio.
In this paper, a revised optimal homotopy asymptotic method (OHAM) is applied to derive an explicit analytical solution of the Falkner-Skan wedge flow problem. The comparisons between the present study with the numerical solutions using (fourth order Runge-Kutta) scheme and with analytical solution using HPM-Padé of order [4/4] and order [13/13] show that the revised form of OHAM is an extremely effective analytical technique.
'Smoker's paradox' is a controversial phenomenon of an unexpected favourable outcome of smokers post acute myocardial infarction. There are conflicting evidences from the literature so far. We investigate for the existence of this phenomenon in our post acute myocardial infarction patients.
Two-wheeled wheelchairs are considered highly nonlinear and complex systems. The systems mimic a double-inverted pendulum scenario and will provide better maneuverability in confined spaces and also to reach higher level of height for pick and place tasks. The challenge resides in modeling and control of the two-wheeled wheelchair to perform comparably to a normal four-wheeled wheelchair. Most common modeling techniques have been accomplished by researchers utilizing the basic Newton's Laws of motion and some have used 3D tools to model the system where the models are much more theoretical and quite far from the practical implementation. This article is aimed at closing the gap between the conventional mathematical modeling approaches where the integrated 3D modeling approach with validation on the actual hardware implementation was conducted. To achieve this, both nonlinear and a linearized model in terms of state space model were obtained from the mathematical model of the system for analysis and, thereafter, a 3D virtual prototype of the wheelchair was developed, simulated, and analyzed. This has increased the confidence level for the proposed platform and facilitated the actual hardware implementation of the two-wheeled wheelchair. Results show that the prototype developed and tested has successfully worked within the specific requirements established.
Optimal nutrition is essential for healthy growth during adolescence. This study aims to investigate the baseline nutritional intake of Malaysian adolescents by gender, body mass index, and places of residence, both urban and rural. A cohort study was conducted consisting of 794 adolescents (aged 13-years) attending 15 public secondary schools from the Central (Kuala Lumpur and Selangor) and Northern (Perak) Regions of Peninsular Malaysia. Qualified dietitians conducted a 7-day historical assessment of habitual food intakes. Facilitated by flipcharts and household measurement tools, detailed information on portion sizes and meal contents were recorded. Nutritionist Pro™ Diet Analysis software was also used to analyze the dietary records.The mean age of the adolescents was 12.86 ± 0.33 y; the mean energy intake was 1659.0 ± 329.6 kcal/d. Males had significantly (P < .001) higher energy intake than females (1774.0 ± 369.8 vs 1595.2 ± 320.6 kcal/d); adolescents in rural schools consumed more energy and cholesterol (P < .001) compared to adolescents in urban schools (1706.1 ± 377.7 kcal/d and 244.1 ± 100.2 mg/d, respectively). Obese adolescents in rural schools consumed more energy and sugar (1987.6 ± 374.0 kcal/d and 48.9 ± 23.0 g/d) (p-value <0.001).The dietary intake of normal weight versus obese adolescents differs by the location of their school. Thus, the implementation of a structured and tailored intervention is recommended to help minimize this nutritional inequality.
MeSH terms: Adolescent; Energy Intake*; Diet Surveys*; Female; Humans; Income*; Life Style; Longitudinal Studies; Malaysia/epidemiology; Male; Nutritional Status; Risk Factors; Socioeconomic Factors; Diet Records; Body Mass Index; Public Health Surveillance*
Diabetes is a metabolic disease with a prolonged elevated level of glucose in the blood leads to long-term complications and increases the chances for cardiovascular diseases. The present study describes the fabrication of a ZnO nanowire (NW)-modified interdigitated electrode (IDE) to monitor the level of blood glucose. A silver IDE was generated by wet etching-assisted conventional lithography, with a gap between adjacent electrodes of 98.80 μm. The ZnO-based thin films and NWs were amended by sol-gel and hydrothermal routes. High-quality crystalline and c-axis orientated ZnO thin films were observed by XRD analyses. The ZnO thin film was annealed for 1, 3 and 5 h, yielding a good-quality crystallite with sizes of 50, 100 and 110 nm, and the band gaps were measured as 3.26, 3.20 and 3.17 eV, respectively. Furthermore, a flower-modeled NW was obtained with the lowest diameter of 21 nm. Our designed ZnO NW-modified IDE was shown to have a detection limit as low as 0.03 mg/dL (correlation coefficient = 0.98952) of glucose with a low response time of 3 s, perform better than commercial glucose meter, suitable to instantly monitor the glucose level of diabetes patients. This study demonstrated the high performance of NW-mediated IDEs for glucose sensing as alternative to current glucose sensors.
Coastal vegetated ecosystems play an important role in carbon cycling and bacterial communities inhabiting coastal sediments are responsible for the remineralization and processing of organic carbon (OC). We collected 1 m-long sediment cores in Posidonia seagrass meadows from coastal and estuarine sites in Australia that differed in their sedimentary organic and inorganic carbon, nitrogen and mud contents. The metabolic diversity of sediment heterotrophic bacterial communities was characterized at different sediment depths, based on the utilization pattern of 31 individual carbon substrates using Biolog EcoPlatesTM . High metabolic diversity was recorded at both sites, but the carbon substrate utilization rates and the use of carbohydrates were higher at the coastal site compared to the estuarine site. The heterotrophic bacterial community in the coastal sediment appeared to metabolize a more diverse OC pool compared to the estuarine site, which might partly explain the differences in OC storage among the seagrass habitats studied. The Biolog EcoPlatesTM provided a useful tool for characterising the sediment heterotrophic bacterial communities in the meadows and sediment characteristics and biochemical composition of the organic matter played an important role in shaping heterotrophic bacterial communities and their carbon utilization rates, potentially affecting carbon accumulation and preservation within seagrass sediments.
BACKGROUND: Antibiotic overuse is driving the emergence of antibiotic resistance worldwide. Good data on prescribing behaviours of healthcare providers are needed to support antimicrobial stewardship initiatives. This study examined the differences in antibiotic prescribing rates of public and private primary care clinics in Malaysia.
METHODS: We used data from the National Medical Care Survey (NMCS), a nationwide cluster sample of Malaysian public and private primary care clinics in 2014. NMCS contained demographic, diagnoses and prescribing from 129 public clinics and 416 private clinics. We identified all encounters who were prescribed antibiotic and analyse the prescribing rate, types of antibiotics, and diagnoses that resulted in antibiotic.
RESULTS: Five thousand eight hundred ten encounters were prescribed antibiotics; antibiotic prescribing rate was 21.1 % (public clinics 6.8 %, private clinics 30.8 %). Antibiotic prescribing was higher in private clinics where they contributed almost 87 % of antibiotics prescribed in primary care. Upper respiratory tract infection (URTI) was the most frequent diagnosis in patients receiving antibiotic therapy and accounted for 49.2 % of prescriptions. Of the patients diagnosed with URTI, 46.2 % received antibiotic treatment (public 16.8 %, private 57.7 %). Penicillins, cephalosporins and macrolides were the most commonly prescribed antibiotics and accounted for 30.7, 23.6 and 16.0 % of all antibiotics, respectively. More recently available broad-spectrum antibiotics such as azithromycin and quinolones were more frequently prescribed in private clinics.
CONCLUSIONS: Antibiotic prescribing rates are high in both public and private primary care settings in Malaysia, especially in the latter. This study provides evidence of excessive and inappropriate antibiotic prescribing for self-limiting conditions. These data highlights the needs for more concerted interventions targeting both prescribers and public. Improvement strategies should focus on reducing inappropriate prescribing.
Despite its recognized importance for cultural transmission, little is known about the role imitation plays in language learning. Three experiments examine how rates of imitation vary as a function of qualitative differences in the way language is used in a small indigenous community in Oaxaca, Mexico and three Western comparison groups. Data from one hundred thirty-eight 3- to 10-year-olds suggests that children selectively imitate when they understand the function of a given linguistic element because their culture makes frequent use of that function. When function is opaque, however, children imitate faithfully. This has implications for how children manage the imitation-innovation trade-off, and offers insight into why children imitate in language learning across development.
Ionic liquids have been objects of extensive research for physical sorption of CO2 and a number of myths have been perpetuated in the literature, for lack of a critical analysis, concerning their potential for CO2 capture. This study carries a critical analysis of a number of widely accepted ideas and others not so well accepted that have been repeatedly expressed in the literature concerning the CO2 physical sorption in ionic liquids. Using the CO2 solubility in eicosane as benchmark, it will be shown that there is no evidence that ILs display a physical sorption of CO2 larger than n-alkanes when analyzed in adequate concentration units; the fluorination of the ions has no impact on the CO2 solubility and the oxygenation will marginally contribute to a decrease of the solubility. Ionic liquid-based deep eutectic systems are also shown to have a poor CO2 solubility. Although these widely used approaches to physically enhance the CO2 solubility in ILs do not seem to have any positive influence, this does not mean that other types of interaction cannot provide enhanced CO2 solubility as in the case of the anion [B(CN)4] confirmed here by a critical analysis of the published data. The mechanism of CO2 physical sorption in ionic liquids is discussed based on the results analyzed, supported by spectroscopic measurements and molecular simulations previously reported and further suggestions of possibilities for enhanced physical sorption based on fluorinated aromatic rings, other cyano based anions, mixtures with other ILs or solvents or the use of porous liquids are proposed.
OBJECTIVE: Translation of developmental-behavioral screening tools for use worldwide can be daunting. We summarize issues in translating these tools. METHODS: Instead of a theoretical framework of "equivalence" by Pena and International Test Commission guidelines, we decided upon a practical approach used by the American Association of Orthopedic Surgeons (AAOS). We derived vignettes from the Parents' Evaluation of Developmental Status manual and published literature and mapped them to AAOS. RESULTS: We found that a systematic approach to planning and translating developmental-behavioral screeners is essential to ensure "equivalence" and encourage wide consultation with experts. CONCLUSION: Our narrative highlights how translations can result in many challenges and needed revisions to achieve "equivalence" such that the items remain consistent, valid, and meaningful in the new language for use in different cultures. Information sharing across the community of researchers is encouraged. This narrative may be helpful to novice researchers.
The objectives of the present study were to determine the mechanisms of antinociceptive effect of methanol extract of Clinacanthus nutans (Acanthaceae) leaves (MECN) using various animal nociceptive models. The antinociceptive activity of orally administered 10% DMSO, 100 mg/kg acetylsalicylic acid (ASA), 5 mg/kg morphine, or MECN (100, 250, and 500 mg/kg) was determined using the acetic acid-induced abdominal constriction (ACT), formalin-induced paw licking (FT), and hot plate tests (HPT). The role of opioid and nitric oxide/cyclic guanosine monophosphate (NO/cGMP) systems was also investigated. The results showed that MECN produced a significant (p < 0.05) antinociceptive response in all nociceptive models with the recorded ED50 value of 279.3 mg/kg for the ACT, while, for the early and late phases of the FT, the value was >500 mg/kg or 227.7 mg/kg, respectively. This antinociceptive activity was fully antagonized by naloxone (a nonselective opioid antagonist) but was partially reversed by l-arginine (l-arg; a nitric oxide [NO] precursor), Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME; an NO synthase inhibitor), or their combinations thereof. In contrast, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ; a soluble guanylyl cyclase inhibitor) enhanced the extract's antinociception. UHPLC analysis revealed the presence of several flavonoid-based compounds with antinociceptive action. In conclusion, MECN exerted the peripherally and centrally mediated antinociceptive activity via the modulation of the opioid/NO-mediated, but cGMP-independent, systems.
The fish parasites collected from Lutjanus erythropterus fish species showed a correlation with parasitic intensity, fish size, and temperature, and statistical model summary was produced using SPSS version 20, statistical software. Statistical model summary concluded that among the variables which significantly predict the prevalence of Neobenedenia melleni parasites are fish length and water temperature, both significant at 1% and 5%. Furthermore, the increase in one unit of fish length, holding other variables constant, increases the prevalence of parasite by approximately 1 (0.7≈1) unit. Also, increasing the temperature from 32°C to 33°C will positively increase the number of parasites by approximately 0.32 units, holding other variables constant. The model can be summarized as estimated number of Neobenedenia melleni parasites = 8.2 + 0.7 ⁎ (fish length) + 0.32 ⁎ (water temperature). Next, this study has also shown the DNA sequence and parasitic morphology of Neobenedenia melleni. Nucleotide sequence for 18s ribosomal gene RNA in this study showed 99% similarity with N. melleni EU707804.1 from GenBank. Finally, all the sequence of Neobenedenia melleni in this study was deposited in GenBank with accession numbers of KU843501, KU843502, KU843503, and KU843504.
Objective. To compare ultrasound synovial thickness of the 2nd, 3rd and 4th metacarpophalangeal joints (MCPJ) in a group of patients with proven rheumatoid arthritis (RA) and a control group of normal individuals. Materials and Methods. This is a cross-sectional study comprising 30 rheumatoid arthritis patients and 30 healthy individuals. Ultrasound scans were performed at the dorsal side of 2nd, 3rd, and 4th MCPJ of both hands in RA patients and the healthy individuals. Synovial thickness was measured according to quantitative method. The synovial thickness of RA patients and healthy individuals was compared and statistical cut-off was identified. Results. Maximum synovial thickness was most often detected at the radial side of the 2nd MCPJ and 3rd MCPJ and ulnar side of the 4th MCPJ of both hands which is significantly higher (p < 0.05) in RA patients compared to healthy individuals. With high specificity (96%) and sensitivity (90%) the optimum cut-off value to distinguish RA patients and healthy individuals' synovial thickness differs for the radial side of the 2nd and 3rd MCPJ and ulnar side of the 4th MCPJ. Conclusion. Patients with early RA appear to exhibit a characteristic pattern of synovitis which shows radial side predominance in the 2nd and 3rd MCPJ and ulnar side in the 4th MCPJ.
Study site: University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Cocoa is a rich source of polyphenols that has been traditionally used as the treatment of several types of inflammation related disease. The response to inflammation comprises the consecutive release of mediators and the enlistment of circulating leukocytes, such as macrophages. Currently, Cocoa-derived polyphenolics have shown anti-inflammatory effects in vivo, but the therapeutic benefits in vitro remain unclear. Therefore, in this study, the effect of cocoa polyphenolic extract (CPE) on RAW 264.7 macrophage cells sensitized by lipopolysaccharide as in vitro inflammatory model was investigated. The anti-inflammatory activity of CPE was assessed by measuring its ability to inhibit the pro-inflammatory enzyme 5-lipoxygenase (5-LOX) and the pro-inflammatory mediators prostaglandin E2 (PGE2), reactive oxygen species (ROS), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α). The results show that CPE significantly inhibits 5-LOX activity (p
The purpose of the present study was to investigate the interaction between H2S and NO (nitric oxide) in the kidney and to evaluate its impact on the functional contribution of α1A and α1B-adrenoreceptors subtypes mediating the renal vasoconstriction in the kidney of rats with left ventricular hypertrophy (LVH). In rats the LVH induction was by isoprenaline administration and caffeine in the drinking water together with intraperitoneal administration of H2S. The responsiveness of α1A and α1B to exogenous noradrenaline, phenylephrine and methoxaminein the absence and presence of 5-methylurapidil (5-MeU) and chloroethylclonidine (CEC) was studied. Cystathione gamma lyase (CSE), cystathione β synthase (CBS), 3-mercaptopyruvate sulphar transferase (3-MST) and endothelial nitric oxide synthase (eNOS) were quantified. There was significant up regulation of CSE and eNOS in the LVH-H2S compared to the LVH group (P<0.05). Baseline renal cortical blood perfusion (RCBP) was increased (P<0.05) in the LVH-H2S compared to the LVH group. The responsiveness of α1A-adrenergic receptors to adrenergic agonists was increased (P<0.05) after administration of low dose 5-Methylurapidil in the LVH-H2S group while α1B-adrenergic receptors responsiveness to adrenergic agonists were increased (P<0.05) by both low and high dose chloroethylclonidine in the LVH-H2S group. Treatment of LVH with H2S resulted in up-regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways in the kidney. These up regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways enhanced the responsiveness of α1A and α1B-adrenoreceptors subtypes to adrenergic agonists in LVH-H2S. These findings indicate an important role for H2S in modulating deranged signalling in the renal vasculature resulting from LVH development.
Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.
MeSH terms: Breast Neoplasms/diagnosis; Breast Neoplasms/metabolism*; Cell Survival; Doxorubicin/chemistry; Female; Fibroblast Growth Factors/metabolism*; Humans; Phosphorylation; Prognosis; Signal Transduction; Gene Silencing; RNA, Small Interfering/metabolism; Cell Line, Tumor; Proto-Oncogene Proteins c-akt/metabolism; Receptor, Fibroblast Growth Factor, Type 4/metabolism*; MCF-7 Cells
Dental amalgam in fillings exposes workers to mercury. The exposure to mercury was investigated among 1871 dental health care workers. The aim of the study was to evaluate the risk of mercury exposure among dental compared to nondental health care workers and to determine other risk factors for mercury exposure. Respondents answered questionnaires to obtain demographic, personal, professional, and workplace information and were examined for their own amalgam fillings. Chronic mercury exposure was assessed through urinary mercury levels. In total, 1409 dental and 462 nondental health care workers participated in the study. Median urine mercury levels for dental and nondental health care workers were 2.75 μg/L (interquartile range [IQR] = 3.0175) and 2.66 μg/L (IQR = 3.04) respectively. For mercury exposure, there were no significant risk factor found among the workers involved within the dental care. The Mann-Whitney test showed that urine mercury levels were significantly different between respondents who eat seafood more than 5 times per week compared to those who eat it less frequently or not at all (p = 0.003). The urinary mercury levels indicated significant difference between dental workers in their practice using squeeze cloths (Mann-Whitney test, p = 0.03). Multiple logistic regression showed that only the usage of cosmetic products that might contain mercury was found to be significantly associated with the urinary mercury levels (odds ratio [OR] = 15.237; CI: 3.612-64.276). Therefore, mean urinary mercury levels of health care workers were low. Exposure to dental amalgam is not associated with high mercury exposure. However, usage of cosmetic products containing mercury and high seafood consumption may lead to the increase of exposure to mercury.
IMPLICATIONS: Exposure to the high levels of mercury from dental amalgam can lead to serious health effects among the dental health care workers. Nationwide chronic mercury exposure among dental personnel was assessed through urinary mercury levels. Findings suggest low urinary mercury levels of these health care workers. Exposure to dental amalgam is not associated with high mercury exposure. However, the usage of cosmetic products containing mercury and high seafood consumption may lead to the increase of exposure to mercury.