Miracle-dz/UniFAR-FTUs huggingface dataset:
Fucoidan inhibits smooth muscle cell proliferation and reduces mitogen-activated protein kinase activity.

OBJECTIVES AND DESIGN fucoidan has previously been shown to inhibit the proliferation of arterial smooth muscle cells both in animal models and in vitro. However, the mechanisms behind the anti-proliferative effects of this polysulfated polysaccharide are not known in detail. Here, the inhibitory effect of fucoidan on rat aortic smooth muscle cell proliferation was examined and compared with the effects of heparin after stimulation with fetal calf serum, platelet-derived growth factor BB, basic fibroblast growth factor, heparin-binding epidermal growth factor, and angiotensin II. MATERIALS AND METHODS the cultures were analysed with respect to cell proliferation and DNA synthesis by cell counting and measurement of(3)H-thymidine incorporation. Phosphorylation of mitogen-activated protein kinase and nuclear translocation of phosphorylated mitogen-activated protein kinase were studied by immunoblotting and immunocytochemistry. RESULTS fucoidan was shown to be a more potent inhibitor of smooth muscle cell proliferation than heparin. Fucoidan also reduced growth factor-induced activation of mitogen-activated protein kinase and prevented nuclear translocation of phosphorylated mitogen-activated protein kinase. CONCLUSION fucoidan is a more potent anti-proliferative polysulphated polysaccharide than heparin and may mediate its effects through inhibition of the mitogen-activated protein kinase pathway in a similar manner as heparin.
Developmental control of nuclear morphogenesis and anchoring by charleston, identified in a functional genomic screen of Drosophila cellularisation

Morphogenesis of epithelial tissues relies on the precise developmental control of cell polarity and architecture. In the early Drosophila embryo, the primary epithelium forms during cellularisation, following a tightly controlled genetic programme where specific sets of genes are upregulated. Some of them, for example, control membrane invagination between the nuclei anchored at the apical surface of the syncytium. We used microarrays to describe the global programme of gene expression underlying cellularisation and identified distinct classes of upregulated genes during this process. Fifty-seven genes were then tested functionally by RNAi. We found six genes affecting various aspects of cellular architecture: membrane growth, organelle transport or organisation and junction assembly. We focus here on charleston (char), a new regulator of nuclear morphogenesis and of apical nuclear anchoring. In char-depleted embryos, the nuclei fail to maintain their elongated shape and, instead, become rounded. In addition, together with a disruption of the centrosome-nuclear envelope interaction, the nuclei lose their regular apical anchoring. These nuclear defects perturb the regular columnar organisation of epithelial cells in the embryo. Although microtubules are required for both nuclear morphogenesis and anchoring, char does not control microtubule organisation and association to the nuclear envelope. We show that Char is lipid anchored at the nuclear envelope by a farnesylation group, and localises at the inner nuclear membrane together with Lamin. Our data suggest that Char forms a scaffold that regulates nuclear architecture to constrain nuclei in tight columnar epithelial cells. The upregulation of Char during cellularisation and gastrulation reveals the existence of an as yet unknown developmental control of nuclear morphology and anchoring in embryonic epithelia.
Correlation Between Third Trimester Glycemic Variability in Non-Insulin-Dependent Gestational Diabetes Mellitus and Adverse Pregnancy and Fetal Outcomes

Background: Gestational diabetes mellitus (GDM) is a pregnancy-related metabolic complication. Despite optimal glycemic control from self-monitoring blood glucose (SMBG) in non-insulin-dependent GDM, variations in pregnancy outcomes persist. Glycemic variability is believed to be a factor that causes adverse pregnancy outcomes. Continuous glucose monitoring system (CGMS) detects interstitial glucose values every 5 minutes, and glycemic variability data from CGMS during the third trimester may be a predictor of fetal birth weight and pregnancy outcomes. The aim of this study was to investigate correlation between third trimester glycemic variability in non-insulin-dependent GDM and fetal birth weight. Method: This prospective study was conducted in 55 pregnant volunteers with non-insulin-dependent GDM that were recruited at 28 to 32 weeks’ gestation from the outpatient clinic of the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital during the study period of August 1 to December 31, 2016. Patients had CGMS installed for at least 72 hours and glycemic variability data were analyzed. Results: Of 55 enrolled volunteers, the data from 47 women were included in the analysis. Mean CGMS duration was 85.5 ± 12.83 hours. No statistically significant correlation was identified between glycemic variability in third trimester and birth weight percentiles, or between third trimester CGMS parameters and pregnancy outcomes in the study. Conclusion: Based on these findings, third trimester glycemic variability data from CGMS are not a predictor of fetal birth weight percentile, and no significant association was found between CGMS parameters and adverse pregnancy outcomes; thus, CGMS is not necessary in non-insulin-dependent GDM.
Antitumor activities of a cephalosporin prodrug in combination with monoclonal antibody-beta-lactamase conjugates.

7-(Phenylacetamido)cephalosporin mustard (CM) and 7-(4-carboxybutanamido)cephalosporin mustard (CCM) were developed as anticancer prodrugs that could be activated site selectively by monoclonal antibody-beta-lactamase conjugates targeted to antigens present on tumor cell surfaces. Both CM and CCM were hydrolyzed by purified beta-lactamases from Escherichia coli (EC beta L), Bacillus cereus (BC beta L), and Enterobacter cloacae (ECl beta L). This resulted in the release of phenylenediamine mustard (PDM), a potent cytotoxic drug. The Km and kcat values of the reactions were determined, and it was found that ECl beta L effected the hydrolysis of CM and CCM more rapidly than the other enzymes. Conjugates of ECl beta L were prepared by reacting maleimide-substituted F(ab')2 fragments of the monoclonal antibodies L6 and P1.17 to ECl beta L that had been modified with sulfhydryl groups. In vitro experiments indicated that CCM (IC50 = 25-45 microM) was less toxic than PDM (IC50 = 1.5 microM) to H2981 lung adenocarcinoma cells (L6 antigen positive, P1.17 antigen negative) and that immunologically specific prodrug activation took place when the cells were treated with L6-ECl beta L. In vivo experiments in nude mice demonstrated that CCM was less toxic than CM, and that both prodrugs were much less toxic than PDM. Neither CCM nor PDM exerted antitumor activity on subcutaneous H2981 tumors in vivo. However, a significant antitumor effect was obtained in mice that received L6-ECl beta L 96 h prior to the administration of CCM. The effect was immunologically specific (P < 0.05), since a smaller degree of antitumor activity was obtained in mice that received the nonbinding control conjugate P1.17-ECl beta L prior to CCM. (ABSTRACT TRUNCATED AT 250 WORDS)
Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis.

AIMS Atrial fibrillation (AF) is an important morbidity-mortality risk factor, especially in patients with heart failure (HF). Beta-blockers reduce morbidity and mortality in HF. The study was designed to estimate the preventive efficacy of beta-blocker treatment on AF occurrence in patients with HF. METHODS AND RESULTS A systematic review of the literature was performed to identify all clinical trials evaluating beta-blockers' efficacy in HF. Eligible studies had to be randomized, placebo-controlled and providing information on the incidence of AF during follow-up among those with sinus rhythm at baseline. A total of seven studies which included 11 952 patients receiving a background treatment with angiotensin-converting enzyme-inhibitors could be found. Overall, beta-blockers significantly reduced incidence of onset of AF from 39 to 28 per 1000 patient-years: relative risk reduction=27% (95% confidence interval 14-38, P<0.001); heterogeneity test: P=0.096. A same trend of efficacy was observed in all trials except the SENIORS study. In this trial which included aged patients (>70 years) with systolic or diastolic HF, a higher prevalence of AF at baseline (35%) was observed compared with the mean baseline prevalence (13%). CONCLUSION Beta-blockers appear to effectively prevent occurrence of AF in patients with systolic HF.
Non‐palpable breast carcinomas: Correlation of mammographically detected malignant‐appearing microcalcifications and molecular prognostic factors

Screening mammography has greatly increased the number of non‐palpable breast carcinomas diagnosed in asymptomatic women. Malignant‐appearing microcalcifications represent one of the earliest mammographic findings of non‐palpable breast carcinomas. Many studies have attempted to correlate radiological and histological features of malignant‐appearing microcalcifications. In the present study, we evaluated the association between mammographically detected malignant‐appearing microcalcifications and the expression profile of selected biological markers in non‐palpable breast carcinomas. Two hundred and eighty patients with non‐palpable suspicious breast lesions that were detected during screening mammography were studied. All patients underwent mammographically‐guided needle localization‐excision breast biopsy. Histological examination showed 74 (26.4%) carcinomas of various subtypes. Immunohistochemistry was carried out in 58/74 carcinomas by using a panel of monoclonal and polyclonal antibodies against estrogen receptor (ER), progesterone receptor (PR), HER‐2/neu, Bcl‐2, Bax, Fas and DNA fragmentation factor (DFF). Malignant‐appearing microcalcifications was the major mammographic finding in 45/58 (77%) patients. Nuclear ER positivity (65.5%) and PR positivity (46.5%) of non‐palpable breast carcinomas were statistically correlated with malignant‐appearing microcalcifications (p < 0.01 and p < 0.05, respectively). Statistically significant associations were also found between malignant‐appearing microcalcifications and HER‐2/neu positivity (p < 0.01), Bax positivity (p < 0.01), Fas positivity (p < 0.05) and DFF positivity (p < 0.01), whereas no statistical correlation was found with Bcl‐2 positivity (p > 0.05). Malignant‐appearing microcalcifications detected during screening mammography represent a diagnostic, prognostic and therapeutic challenge. The mammographic/biological associations and their potential implications in the management of women with non‐palpable breast carcinomas are thoroughly discussed. © 2002 Wiley‐Liss, Inc.
Hepatocyte antigen expression in subtypes of intestinal metaplasia of the stomach.

OBJECTIVE Recently, hepatocyte antigen (Hep) was introduced as a sensitive and reliable marker of intestinal metaplasia (IM). However, the distribution of Hep expression in subtypes of IM was not described. METHODS We examined the expression of Hep in 58 cases of chronic gastritis associated with IM by immunohistochemical staining. Cases were classified as: 19 of IM Type I (complete) cases, 16 cases of IM Type II (incomplete) and 23 cases of IM Type III (incomplete). The distribution of Hep expression was classified into four groups according to the intensity of Hep expressing metaplastic cells: negative, low, moderate and high. We also compared expression of Hep with that of MUC-1, MUC-2 and MUC-5AC. RESULTS Hep expression showed granular cytoplasmic staining and was specifically identified in columnar cells, but not in goblet cells. There was no significant difference between Hep expression and subtypes of IM (p > 0.005). However the difference between the distribution of Hep expression among three subtypes of IM was significant (p < 0.001). No relationship was observed among the expression of Hep, MUC-1, MUC-2 and MUC-5AC. CONCLUSION Results of the present study revealed that the distribution of Hep expression is high in the majority of the complete type (Type I) IM cases, moderate in the majority of the incomplete Type II IM cases and low in all of the incomplete Type III IM cases and suggest that besides its role as a sensitive marker in IM, the evaluation of the distribution of Hep expression might be useful in the classification of IM.
Heme oxygenase 1 expression induced by IL‐10 requires STAT‐3 and phosphoinositol‐3 kinase and is inhibited by lipopolysaccharide

Heme‐oxygenase 1 (HO‐1) is a stress‐response protein with anti‐inflammatory activity. This study has examined the regulation of HO‐1 expression by the anti‐inflammatory factor, interleukin (IL)‐10 and whether HO‐1 could account for the function of the cytokine. IL‐10‐induced expression of HO‐1 required the activation of signal transducer and activator of transcription (STAT)‐3 but not p38 mitogen‐activated protein kinase. However, expression of HO‐1 also required the activation of the phosphatidylinositol‐3 kinase pathway, a signaling mechanism not required for the anti‐inflammatory activity of IL‐10. Moreover, induction of HO‐1 expression was not restricted to IL‐10, as IL‐6, a cytokine known to activate STAT‐3, could also induce the protein. In human macrophages, lipopolysaccharide inhibited HO‐1 expression induced by IL‐10 Also, inhibition of HO‐1 activity by the specific inhibitor zinc‐II‐protoporphyrin‐IX had no effect on the anti‐inflammatory function of IL‐10. In summary, although IL‐10 does regulate HO‐1 expression, it does not appear to play a significant role in the anti‐inflammatory activity of the cytokine.
Comparisons of sexual behaviors and STD prevalence among older and younger individuals with HIV infection

Abstract Knowledge of an HIV-infected individual's sexual behaviors and routine sexually transmitted diseases (STDs) testing greatly facilitates HIV prevention efforts, but current data in older individuals are lacking. This study was developed to compare sexual behaviors and STD prevalence between older HIV-infected individuals and their younger counterparts. We conducted a cross-sectional cohort study of HIV-infected individuals ≥18 years who completed an annual behavioral assessment. A total of 541 individuals completed the assessment. Analyses were performed to examine differences in sexual behaviors and STD prevalence between age groups: younger (18–35 years) (30%), middle-aged (36–49 years) (46%), and older (≥50 years) (24%). Older individuals were most likely to be male and Caucasian with longest time since HIV diagnosis, greatest receipt of highly active antiretroviral therapy (HAART), and highest rates of HIV RNA <50 copies/mL (all p<0.001). Reports of recent sexual activity decreased with age, younger (56%) vs. middle-aged (43%) vs. older (27%) (p<0.001). The median number of recent sex partners was one (range 1–25) and 68% overall reported using condoms consistently; these parameters did not differ by age group. STD prevalence was 8% (gonorrhea [9], chlamydia [7], and syphilis [20]) and was highest among younger individuals (younger [11%] vs. middle-aged [7%] vs. older [3%]). Our results demonstrated that with older age, sexual activity declines but inconsistent condom use remains commonly reported. Furthermore, STDs were identified among all age groups. This latter finding reinforces the need for secondary prevention efforts among all individuals living with HIV/AIDS.
Results from AMBER, a randomized phase 2 study of bevacizumab and bortezomib versus bortezomib in relapsed or refractory multiple myeloma

Newer systemic therapies have significantly advanced the treatment of multiple myeloma, but additional agents are needed. Bortezomib is a proteasome inhibitor with efficacy in relapsed/refractory multiple myeloma that inhibits tumor angiogenesis, a process that has been implicated in multiple myeloma pathogenesis.
Comparison of macular choroidal thickness among patients older than age 65 with early atrophic age-related macular degeneration and normals.

PURPOSE To compare macular choroidal thickness between patients older than 65 years with early atrophic age-related macular degeneration (AMD) and normals. METHODS This was a consecutive, cross-sectional observational study. Enhanced depth imaging spectral-domain optical coherence tomography using horizontal raster scanning at 12 locations throughout the macula was performed in one eye of consecutive patients presenting with large soft drusen alone, drusen with additional features of early AMD, or a normal fundus. Choroidal thickness was measured at 7 points for each raster scan in the central 3 mm of the macula (total 84 points per eye). In addition, a single subfoveolar measurement was obtained for each eye. RESULTS One hundred fifty eyes of 150 patients were included. There was no significant difference between mean refractive error for each diagnosis category via one-way ANOVA (P = 0.451). Mean macular choroidal thickness (CT) was 235 ± 49 μm (range, 125-334 μm; median 222 μm) for normals, 161 ± 39 μm (range, 89-260 μm; median = 158 μm) for the drusen group, and 115 ± 40 μm (range, 22-256 μm; median = 112 μm) for patients with AMD. Mean macular CT was significantly different via one-way ANOVA among all diagnosis categories (P < 0.001). CONCLUSIONS The presence of features of early AMD without geographic atrophy and/or soft drusen alone is associated with decreased mean macular CT in vivo compared to that in patients with no chorioretinal pathology. Using enhanced depth imaging, measurement of a single subfoveolar choroidal thickness is highly correlated to mean central macular CT.
The effectiveness of psychological treatments for chronic pain in older adults: cautious optimism and an agenda for research

Purpose of review To explores the potential role of psychological treatments for older people who are affected by chronic pain. Recent findings It is now widely recognized that chronic pain is a highly prevalent health problem among older people, and guidelines have evolved to assist with the assessment and management of chronic pain. However, despite the fact that psychological treatments have been shown to be effective for a range of other conditions such as depression and anxiety, there is a relative paucity of studies focused on pain management. Although more evidence is needed, the trend from existing studies indicates that older people find psychological treatments for chronic pain to be relevant, acceptable in content, and beneficial in reducing distress and disability. Particular challenges arise for the delivery of psychological interventions to people with pain and cognitive impairment associated with dementia. There is a growing interest in this population and a good deal of research has focused on the assessment of pain, but with a small number of exceptions, almost no research activity as yet in developing psychological treatments for people with pain and dementia. Summary We conclude that there is sufficient evidence that psychological interventions are efficacious for older people with chronic pain. We propose a number of areas for research focus over the next 10 years that will help to consolidate our knowledge and to explore new avenues for the psychological management of chronic pain in older people.
A comparative study of Simple Mail Transfer Protocol (SMTP), Post Office Protocol (POP) and X.400 Electronic Mail Protocols

We present the main features and functionality of the three most widely used message transfer protocols. We study actual implementations and base our analysis on benchmarking. The performance of the protocols is compared in terms of end to end delay, volume of traffic and number of frames generated at the physical layer and frame length distribution. An analytical model is proposed for the approximation of the upper and lower bounds of volume generated by SMTP which can easily be extended for POP3. The model considers both explicit and piggyback acknowledgements at the TCP layer.
Lipopolysaccharide alters suckling rat liver glycogenolysis.

Gram-negative sepsis/septic shock in the newborn continues to be a major medical problem, causing high mortality. Hyperglycemia followed by hypoglycemia is a common symptom in endotoxic shock. However, the mechanism of newborn glucoregulatory response to endotoxin has not been well understood. Paradoxically, monocyte-phagocytes can contribute to shock by overwhelming secretion of cytokines and also host defense by detoxifying endotoxin. Since monocyte-phagocyte function is immature in the newborn, this study was performed to evaluate Kupffer cell's role in liver glycogenolysis during endotoxic shock. Endotoxin (LPS) induced hyperglycemia in 10-day-old rats, and increased net glucose output in the isolated perfused liver. 1) Cytarabine decreased Kupffer cell function (decreased hepatic colloid carbon uptake) and blunted LPS-increased liver net glucose output in the Cytarabine + LPS-treated group (104 +/- 4 vs. 146 +/- 3 micrograms/min/g wet liver in the LPS-treated group: P < .001). 2) Indomethacin (IND) suppressed LPS-induced liver net glucose output in the LPS + IND-treated group (133 +/- 5 vs. 146 +/- 3 micrograms/min/g wet liver, P < .05). Thus, prostaglandins were suggested to contribute to glycogenolysis in the 10-day-old rat liver. 3) Phorbol 12-myristate 13-acetate (PMA) increased liver net glucose output (166 +/- 4 micrograms/min/g wet liver), and H-7, a protein kinase C inhibitor, blunted PMA-induced liver glucose output (140 +/- 2 micrograms/min/g wet liver, P < .05). H-7 enhanced LPS-induced liver net glucose output (196 +/- 9 micrograms/min/g wet liver, P < .01). Therefore, protein kinase C may not be the dominant cell signaling system for LPS stimulation in suckling rat Kupffer cells.
A First Cut Estimate of the Equity Risk Premium in India

We estimate the equity risk premium in India using data for the last 25 years. We address the shortcomings of existing indices by constructing our own total return index for the 1980s and early 1990s. We use our estimates of the extent of financial repression during this period to construct a series of the risk free rate in India going back to the early 1980s. We find that the equity risk premium is about 8¾% on a geometric mean basis and about 12½% on an arithmetic mean basis. There is no significant difference between the pre reform and post reform period: the premium has declined marginally on a geometric mean basis and has risen slightly on an arithmetic mean basis. The reason for this divergence between the sub period behaviour of the two means is the increase in the annualized standard deviation of stock market returns from less than 20% in the pre reform period to about 25% in the post reform period. The higher standard deviation depresses the geometric mean in the post reform period.