The gene for the mouse low affinity receptor for IgE (Fc epsilon RII, also known as CD23) was mapped on Chromosome (Chr) 8 proximal to Plat. This gene, symbolized Fcer2 (formerly Fce2) resides in a region of Chr 8 with linkage homology with human chromosomes 8 and 19. The mouse Fc epsilon RII was examined for the presence of alternate N-terminal forms such as seen in humans. An antisense RNA probe was prepared from the 5' end of the cDNA through the first 660 bp of the cDNA and was used to analyze message from Fc epsilon RII+ B cells and B cell hybridomas both before and after treatment with interleukin 4 (IL-4). Using RNase protection analysis, a major 640 bp band corresponding to the full length probe was seen, even after activation of the cells with LPS in the presence of IL-4, which is known to give high expression levels of the Fc epsilon RII. This result suggests that the mouse does not produce significant levels of an alternate IL-4 inducible Fc epsilon RII, as seen in man, and this may explain the more restricted cell lineage expression of the Fc epsilon RII in the mouse.

Although lung protection with low tidal volume and limited plateau pressure (P_plat) improves survival in acute respiratory distress syndrome patients (ARDS), the best way to set positive end-expiratory pressure (PEEP) is still debated.

This study aimed to compare two strategies using individual PEEP based on a maximum P_plat (28-30 cmH₂O, the Express group) or on keeping end-expiratory transpulmonary pressure positive (0-5 cmH₂O, P_Lexpi group). We estimated alveolar recruitment (Vrec), end-expiratory lung volume and alveolar distension based on elastance-related end-inspiratory transpulmonary pressure (P_L,EL).

Nineteen patients with moderate to severe ARDS (PaO₂/FiO₂ < 150 mmHg) were included with a baseline PEEP of 7.0 ± 1.8 cmH₂O and a PaO₂/FiO₂ of 91.2 ± 31.2 mmHg. PEEP and oxygenation increased significantly from baseline with both protocols; PEEP Express group was 14.2 ± 3.6 cmH₂O versus 16.7 ± 5.9 cmH₂O in P_Lexpi group. No patient had the same PEEP with the two protocols. Vrec was higher with the latter protocol (299 [0 to 875] vs. 222 [47 to 483] ml, p = 0.049) and correlated with improved oxygenation (R² = 0.45, p = 0.002). Two and seven patients in the Express and P_L,expi groups, respectively, had P_L,EL > 25 cmH₂O.

There is a great heterogeneity of P_Lexpi when P_plat is used to titrate PEEP but with limited risk of over-distension. A PEEP titration for a moderate positive level of P_Lexpi might slightly improve alveolar recruitment and oxygenation but increases the risk of over-distension in one-third of patients.

BACKGROUND

In the murine cornea, which is an established model for analyzing pathologic lymphatic vessel growth, phenotypic heterogeneity of the endogenous lymphatic vessels in the limbus of the cornea was previously described. In this study, the cornea of BALB/c, C57BL/6, and FVB mice with different limbal lymphangiogenic phenotypes was analyzed to identify novel candidates potentially influencing lymphatic vessel growth.

RESULTS

Pathway specific expression analysis of the cornea was performed to identify novel candidate genes. Corneal protein expression of the respective candidates was analyzed by fluorescent immunohistochemistry. The effect of the candidates on proliferation of human dermal lymphatic endothelial cells (HDLECs) was analyzed by BrdU proliferation ELISA. Thirteen genes were differentially regulated in corneas of mouse strains with more endogenous limbal lymphatic vessels (high-lymphangiogenic) (C57BL/6) compared to mouse strains with less endogenous limbal lymphatic vessels (low-lymphangiogenic) (BALB/c, FVB). Two candidates, Tumor necrosis factor (ligand) superfamily member 10 (Tnfsf10/Trail) and Plasminogen activator, tissue (Plat/tPA) were expressed in the cornea of BALB/c and C57BL/6 mice on the protein level. In vitro, Trail and recombinant tPA inhibited the proliferation of human dermal lymphatic endothelial cells.

CONCLUSIONS

Molecular analysis of the naive cornea in mouse strains with different limbal lymphatic phenotypes is a valuable model to identify novel endogenous regulators of lymphangiogenesis.

The follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) are malignant and benign thyroid neoplasms, respectively. MicroRNA (miRNA) expressions have been touted as an indicator for prognostic outcome in thyroid cancer. The study objective was to explore genes suppressed by miRNA-21-3p and miRNA-21-5p for potential therapeutic insights. Differentially expressed genes and their functional enrichment were obtained from 25 FTA and 27 FTC gene microarray dataset GSE82208 using R and Bioconductor tools. The miRNA target sites were obtained from miR-TarBase database. A unique gene list of differentially expressed FTC and FTA were entered into miR-TarBase database to obtain target genes for both miRNA-21-3p and miRNA-21-5p. The result showed that miRNA-21-3p and miRNA-21-5p downregulated TIMP3, MAT2A, TGFBR2, and PLAT gene in FTC and FTA leading to significant expression of acute phase-response to metallothionein, metal ions, and unfolded protein response (UPR). The computational analysis suggests that the suppression of miRNA-21-3p and miRNA-21-5p could be an intervention strategy for therapeutically targeting FTC and FTA treatments.

Keywords: Gene expression; microRNA; molecular markers; thyroid tumor.

SARS-CoV-2 has spread rapidly across the world and is negatively impacting the global human population. COVID-19 patients display a wide variety of symptoms and clinical outcomes, including those attributed to genetic ancestry. Alu retrotransposons have played an important role in human evolution, and their variants influence host response to viral infection. Intronic Alus regulate gene expression through several mechanisms, including both genetic and epigenetic pathways. With respect to SARS-CoV-2, an intronic Alu within the ACE gene is hypothesized to be associated with COVID-19 susceptibility and morbidity. Here, we review specific Alu polymorphisms that are of particular interest when considering host response to SARS-CoV-2 infection, especially polymorphic Alu insertions in genes associated with immune response and coagulation/fibrinolysis cascade. We posit that additional research focused on Alu-related pathways could yield novel biomarkers capable of predicting clinical outcomes as well as patient-specific treatment strategies for COVID-19 and related infectious diseases.

Keywords: ACE; COVID-19; F13B; Human evolution; PGR; PLAT; SARS-CoV-2.

Genes of the PLAT protein family, including PLAT and ATS3 subfamilies of higher plants and homologs of liverwort, are involved in plant defense against insects. Laticifer cells in plants contain large amounts of anti-microbe or anti-insect proteins and are involved in plant defense against biotic stresses. We previously found that PLAT proteins accumulate in laticifers of fig tree (Ficus carica) at comparable levels to those of chitinases, and the transcript level of ATS3, another PLAT domain-containing protein, is highest in the transcriptome of laticifers of Euphorbia tirucalli. In this study, we investigated whether the PLAT domain-containing proteins are involved in defense against insects. Larvae of the lepidopteran Spodoptera litura showed retarded growth when fed with Nicotiana benthamiana leaves expressing F. carica PLAT or E. tirucalli ATS3 genes, introduced by agroinfiltration using expression vector pBYR2HS. Transcriptome analysis of these leaves indicated that ethylene and jasmonate signaling were activated, leading to increased expression of genes for PR-1, β-1,3-glucanase, PR5 and trypsin inhibitors, suggesting an indirect mechanism of PLAT- and ATS3-induced resistance in the host plant. Direct cytotoxicity of PLAT and ATS3 to insects was also possible because heterologous expression of the corresponding genes in Drosophila melanogaster caused apoptosis-mediated cell death in this insect. Larval growth retardation of S. litura occurred when they were fed radish sprouts, a good host for agroinfiltration, expressing any of nine homologous genes of dicotyledon Arabidopsis thaliana, monocotyledon Brachypodium distachyon, conifer Picea sitchensis and liverwort Marchantia polymorpha. Of these nine genes, the heterologous expression of A. thaliana AT5G62200 and AT5G62210 caused significant increases in larval death. These results indicated that the PLAT protein family has largely conserved anti-insect activity in the plant kingdom (249 words).

Keywords: Anti-herbivore protein; Anti-pest protein; Insecticidal protein; Latex; Raphanus sativus; Tsukuba system.

Neovastat® is a standardized extract of marine cartilage, an avascular tissue, which contains many biologically active molecules and has multiple antiangiogenic properties. In addition to VEGFR2 and MMPs inhibition, shark cartilage extract (SCE) has recently been shown to induce tissue plasminogen activator gene (PLAT) expression in bovine endothelial cells in a TNF like manner, by inducing the typical mediators NF-κB and JNK. There is now compelling evidences that the NF-κB and JNK pathways are activated by cytokines induced generation of reactive oxygen species (ROS). We used macroarray genes expression analysis on human umbilical vein endothelial cells, to investigate if that mechanism could mediate the effect of SCE. Transcriptomic results showed that SCE induced expression of several cytokines. Their impact must be important, given that treatment of endothelial cells with the cytokine TNF-α was able to reproduce most of the effects of cartilage extract on genes expression. In addition, most of the genes, known to be inducible by NF-κB or JNK following cytokines stimulation, were less induced by SCE when endothelial cells were pretreated with the antioxidant N-Acetylcysteine (NAC), suggesting a role of ROS in endothelial cell activation by SCE. Finally, the possible effects of PLAT, PLG, SELE, IL8 and PRDX2 (those validated by q-PCR) on angiogenesis, will also be discussed.

Purpose: To test the efficacy of a plateau in heart rate (HR_plat) as an effective indicator for confirming [Formula: see text]max attainment in a middle-aged to older sample.

Methods: Nine men and eleven women (age 60 ± 8.5 years, [Formula: see text]max 35.9 ± 9.4 ml/kg/min, N = 20) completed a single [Formula: see text]max test on both the treadmill and cycle ergometer.[Formula: see text]max was confirmed using a plateau in [Formula: see text] ([Formula: see text]_plat) of ≤ 150 ml/min, a verification bout, and HR_plat (≤ 4 bpm).

Results: [Formula: see text]_plat occurred in 100% and 95% of participants on the treadmill and cycle ergometer, respectively. Verification criteria ([Formula: see text]max during verification ≤ 2% of [Formula: see text]max during incremental test) were met by 80% of participants on both modalities. HR_plat was achieved by 90% and 70% of participants on the treadmill and cycle ergometer, respectively.

Conclusion: These results suggest that a verification bout is reliable for confirming [Formula: see text]max in older adults on both modalities. In our sample of middle-aged and older adults, [Formula: see text]_plat was the most robust method to assess [Formula: see text]max when indirect calorimetry is available. Although more research is warranted, when indirect calorimetry is not available, a HR_plat of ≤ 4 bpm may be a useful alternative to get an accurate representation of maximal effort in middle-aged and older adults.

Keywords: Age; Criteria; Plateau; Verification; max; peak.

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has developed into a pandemic causing major disruptions and hundreds of thousands of deaths in wide parts of the world. As of July 3, 2020, neither vaccines nor approved drugs for effective treatment are available. In this article, we showcase how to individuate drug targets and potentially repurposable drugs in silico using CoVex a recently presented systems medicine platform for COVID-19 drug repurposing. Starting from initial hypotheses, CoVex leverages network algorithms to individuate host proteins involved in COVID-19 disease mechanisms, as well as existing drugs targeting these potential drug targets. Our analysis reveals GLA, PLAT, and GGCX as potential drug targets, and urokinase, argatroban, dabigatran etexilate, betrixaban, ximelagatran and anisindione as potentially repurposable drugs.

Keywords: SARS-CoV-2; network-based drug repurposing; systems medicine.

Objective: Solid tumors often establish a procoagulable state that can lead to venous thromboembolism (VTE). Although some of the key genes involved in this process are known, no previous study has compared the "coagulome", i.e., the expression of coagulation/fibrinolysis genes, across different primary tumor types. It is also unclear whether the coagulome is associated with specific characteristics of the tumor microenvironment (TME). We aimed to address this question.

Methods: We analyzed the expression of the genes F3, PLAU, PLAT, PLAUR, SERPINB2, and SERPINE1 in 32 cancer types using data from The Cancer Genome Atlas (TCGA) and other freely available resources.

Results: We identified specific expression patterns of procoagulant and fibrinolytic genes. The expression of the Tissue Factor (F3) was found to be tumor type dependent, with the highest expression in glioblastoma (GBM), a highly procoagulable tumor type. Conversely, high expression of the fibrinolysis gene cluster PLAU, PLAUR, SERPINE1 was consistently linked to the characteristics of the TME (monocytic infiltration) and high expression of important checkpoints of the immune response, such as PD-L2 and CD276/B7-H3.

Conclusion: These tumor-specific patterns of expression might partially explain the differences in VTE risk among tumor types. We propose that biomarkers of coagulation fibrinolysis might provide valuable information about the TME in cancer patients.

Keywords: Cancer-associated thrombosis; Coagulome; Fibrinolysis; The Cancer Genome Atlas (TCGA); Tissue factor; Tumor microenvironment.

OBJECTIVE

To investigate the morphological characteristics of the mandibular first premolars in people from Pearl River Delta region in Guangdong province using three techniques, including periapical radiographs, the radiographs with files inserted the canals and the clearing technique.

METHODS

A total of 363 extracted mandibular first premolars were collected and numbered. Two preoperative radiographs were taken in buccolingual and mesiodistal directions respectively. After access opening, the files were placed in the canals and two other radiographs were taken. The mandibular first premolars with multi-canal system were selected and observed under dental operating microscope (DOM). The mandibular first premolars were made transparent and were categorized using the Vertucci's classification.

RESULTS

There were different results among the three approaches. Periapical radiographs could be used to distinguish only between one and multiple canals systems. The incidence of multiple canals was 33.33% from the radiographs with file. The mandibular first premolars had a high frequency (34.44%) of multi-canal system by clearing method. The root canal morphology of the mandibular first premolars showed great variance. The canal orifices of the mandibular first premolars with one or two canal distributed in a buccolingual line. The floor of pulp chamber of the mandibular first premolars with three or four canals was a plat form.

CONCLUSIONS

The mandibular first premolars have a high frequency multi-canal system and could be classified in many categories. Using DOM and radiographs with file is a useful way in judging the canal numbers and categories.

BACKGROUND

Central serous chorioretinopathy (CSC) is a common chorioretinal disease, characterized by choroidal hyperpermeability leading to neurosensory and/or retinal pigment epithelial detachments. Hypofibrinolysis due to higher plasma concentrations of plasminogen activator type 1 (PAI-1) or lower activity of tissue-type plasminogen activator (t-PA) has been implicated in the pathogenesis of CSC. Functional polymorphisms in the PAI-1 (SERPINE1) and t-Pa (PLAT) are thus potential risk factors for CSC. The aim of the present study was therefore to investigate a hypothesized association between the PAI-1 4G/5G and the t-PA -7351C>> T gene variants and the presence of CSC.

METHODS

The present study comprised 172 CSC patients and 313 control subjects. Genotypes of the PAI-1 4G/5G and the t-PA -7351C>> T polymorphisms were determined by TaqManTM fluorogenic 5'-exonuclease assays.

RESULTS

Allelic frequencies or genotype distributions of neither the PAI-1 4G/5G nor the t-PA -7531C>> T polymorphisms were significantly different between patients with CSC and control subjects (PAI-1 4G/4G: 24.4% vs. 20.4, p = 0.36; t-PA -7351CC: 42.4% vs. 46.0%, p = 0.50). After adjusting for age and gender presence of the PAI-1 4G/4G genotype was associated with a non-significant odds ratio (OR) of 1.21 (95% confidence interval [95% CI]: 0.77-1.92, p = 0.41), while homozygosity for the t-PA -7351C allele yielded a non-significant OR of 0.91 (95% CI: 0.62-1.33, p = 0.62) for CSC.

CONCLUSIONS

The present study suggests that both the t-PA -7351C>> T and the PAI-1 4G/5G gene variants are unlikely major risk factors for CSC.

Embryonic stem (ES) cells have been considered as a valuable renewable source of materials in regenerative medicine. Recently, we identified the homeoprotein EGAM1 both in preimplantation mouse embryos and mouse ES cells. Expression of the Egam1 transcript and its encoded protein was detectable in differentiating mouse ES cells, while it was almost undetectable in undifferentiated cells. In the present study, in order to clarify the effect of forced expression of EGAM1 on the differentiation of mouse ES cells in vitro, transfectants expressing exogenous EGAM1 were generated. Egam1 transfectants promoted differentiation into cell types expressing Gata6, Gata4, Afp, or Plat, genes associated with emergence of the extra-embryonic endoderm lineages. On the other hand, Egam1 transfectants inhibited the expression of specific genes for the embryonic lineages, including Fgf5 (epiblast) and T (mesoderm), in addition to Cdx2, a specific gene for the extra-embryonic trophectoderm lineages. Changes in the percentage of cells recognizing by antibodies against specific marker proteins closely correlated with the expression patterns of their transcripts. Taken together, the results obtained in this study suggested that mouse ES cells expressing exogenous EGAM1 preferentially differentiate into extra-embryonic primitive endoderm lineages, rather than embryonic lineages or extra-embryonic trophectoderm lineages.

The concepts of power and representation hold a particular significance for the nursing profession. Joanna Du Plat-Jones examines their effects for both nurses and clients.

The objective of this study was to explore the effects of mulching patterns on soil water, growth, photosynthetic characteristics, grain yield and water use efficiency (WUE) of broomcorn millet in the dryland of Loess Plateau in China. In a three-year field experiment from 2011 to 2013, we compared four different mulching patterns with traditional plat planting (no mulching) as the control (CK). The mulching patterns included W ridge covered with common plastic film + intredune covered with straw (SG), common ridge covered with common plastic film + intredune covered with straw (LM), double ridges covered with common plastic film + intredune covered with straw (QM), and the traditional plat planting covered with straw (JG). The results showed that the soil water storage in 0-100 cm layer was significantly higher in all mulching patterns than in CK, particularly in SG then followed by LM, QM and JG, and the differences among the mulching patterns reached a significant level at the different growth stages of broomcorn millet. Among all mulching patterns, SG had the greatest effect on the growth and photosynthesis of broomcorn millet, respectively increasing the yield and WUE by 55.9% and 64.9% over CK, and the differences among the mulching patterns also reached a significant level. Therefore, SG was recommended as an efficient planting pattern for broomcorn millet production in the dryland of Loess Plateau in China.

The National Children's Study (NCS) is a longitudinal study that will examine the influence of environmental and social factors on the health and development of 100,000 children, following them from before birth until age 21. Proposed participant recruitment methods call for locating and listing all dwelling units (DUs) located within randomly selected segments within the 105 NCS sites. One of seven Vanguard Centers of the NCS includes four rural counties that span approximately 2,500 square miles. The size of this sampling area presents unique geographic challenges. In order to determine the most efficient method for listing DUs within this large area, a study was undertaken to investigate the differences in the percent of DUs identified and the cost of four different approaches. It compared the on-site listing method of physically identifying each DU with three other methods: plat maps, postal listings, and Geographic Information Systems (GIS)/satellite imagery techniques. The on-site method had the strongest kappa (.85) in terms of identifying true DUs. There was a moderate agreement (.59) with the plat map method, fair agreement (.34) with the postal method, and only a slight agreement (.14) with the GIS/satellite imagery method. The plat map, postal listing, and GIS/satellite methods were less time-consuming than the on-site method.

OBJECTIVE

The aim of the study was compare the prognostic value, efficacy and safety ofpositive end-expiratory pressure (PEEP) adjustment in conformity with lower inflection point of static "pressure-volume" loop (LIP) or end-expiratory esophageal pressure (EEEP) in parenchymal respiratory failure.

METHODS

We included in the study 56 patients (39 males) at age 47 +/- 17.8 years with parenchymal respiratory failure (PaO2/FiO2 < 250 mmHg, bilateral infiltrates on chest X-ray or lung CT scan, no signs of left ventricular failure), who were mecAanically ventilated for less than 48 hours. All patients were sedated and paralyzed. We measured intra- Sabdominal pressure, PaO2/FiO2, PaCO2, alveolar dead space (Vdalv), plotted static "pressure-volume" loop by low flow technique in range of 0 to 40 mbar, recording LIP Then we placed nasogastric tube with balloon for esophageal pressure measurement and measured esophageal pressure at PEEP range from 8 to 20 mbar (with 2 mbar steps) and recorded plateau pressure (Pplat), transpulmonary plateau pressure (Ptp plat), transpulmonary pressure at PEEP level (Ptp PEEP), static compliance of respiratory system (Cstat), lung compliance (Clung), chest wall compliance (Ccw) at every step. Also by volumetric capnography technique we measured end-tidal carbon dioxide concentration (EtCO2), minute volume of exhaled carbon dioxide (VCO2) volume of exhaled carbon dioxide by single breath (VtCO2) and calculate VC2/EtCO2 as a surrogate marker of pulmnonary perfusion. After that we set PEEP at EEEP level (at zero end-expirato- my ranspulmonary pressure) and recorded changes of PaO2/FiO2 and Vdalv.

RESULTS

LIP value was 5 (6-10) mbar and it was less than empirically set PEEP in most of patients before enrollment and had no prognostic value for PEEP setting. EEEP level was 14 (12-18.25) mbar and it was higher than LIP in 96.4% patients. Distribution of EEEP values was close to normal unlike LIP Chest wall compliance was less than normal (100 ml/mbar) in 46% of patients. EEEP has correlation with body mass index (rho 0.554, p=0.002). We did not find any correlation between intra-abdominal pres- sure (IAP) and EEEP (p=0.376) or IAP and LIP (p=0.464). PEEP levels higher than 14 mbar led to significant decrease in Cstat and Clung (p<0.001). We observed significant decrease in VCO at PEEP levels more than 16 mbar, i.e., more than EEEP median. PEEP levels more than 16 mbar decreased VCO2/EtCO2, (decreased pulmonary perfusion) from 7.47 (6.54-8.7) at PEEP 14 mbar to 7.32 (6.35-8.76) at PEEP 20 mbar (p=0.004). PEEP setting at EEEP level increased PaO/FiO2 from 205 (154-235) to 280 (208-358) mmHg (p<0.001), did hot change Vdalv (p=0.093) and decreased Cstat and Clung in the most of patients (64.3%).

CONCLUSIONS

L1P was lower than empirically set PEEP in most patients and did not help to optimize gas exchange. PEEP setting at EEEP level in patients with parenchimal respiratory failure increases PaO/FiO, (reflects opening of collapsed alveoli), decreases volume of expired carbon dioxide and decreases lung compliance (reflects overdistenion of opened alveoli). VCO2/EtCO2 ratio decreases (decreased pulmonary perfusion) at PEEP levels more than 16 mbar, which was more than EEEP.

Elevated plasma levels of lipoprotein(a) [Lp(a)] have been associated with an increased risk of cardiovascular disease. The aim of the present study was to investigate whether Lp(a) plasma levels were associated with subsequent ischemic events and with fibrinolytic variables in patients with established atherosclerotic disease enrolled in the prospective PLAT study. Lp(a) levels and fibrinolytic variables in 37 atherosclerotic patients who subsequently developed an atherothrombotic event during the first year of follow-up (cases) were compared with those in paired controls, matched for age, sex, diagnosis at enrollment and lipid pattern, who remained free from vascular events during the same time frame. Median and mean Lp(a) levels were similar in cases (6.05 mg/dl; 13.8 +/- 19.4 mg/dl) and controls (6.05 mg/dl; 17.1 +/- 21.6 mg/dl). In the whole group plasma Lp(a) levels correlated significantly with the increase of t-PA antigen (r = 0.368; p = 0.002) and fibrinolytic activity (r = 0.410; p = 0.001) induced by venous stasis but not with baseline fibrinolytic variables. These findings indicate that in patients with established atherosclerotic disease Lp(a) may interfere in vivo with the fibrinolytic process but is not predictive of subsequent ischemic events.

Electromagnetic fields play an essential role in cellular functions interfering with cellular pathways and tissue physiology. In this context, Quantum Molecular Resonance (QMR) produces waves with a specific form at high-frequencies (4-64 MHz) and low intensity through electric fields. We evaluated the effects of QMR stimulation on bone marrow derived mesenchymal stromal cells (MSC). MSC were treated with QMR for 10 minutes for 4 consecutive days for 2 weeks at different nominal powers. Cell morphology, phenotype, multilineage differentiation, viability and proliferation were investigated. QMR effects were further investigated by cDNA microarray validated by real-time PCR. After 1 and 2 weeks of QMR treatment morphology, phenotype and multilineage differentiation were maintained and no alteration of cellular viability and proliferation were observed between treated MSC samples and controls. cDNA microarray analysis evidenced more transcriptional changes on cells treated at 40 nominal power than 80 ones. The main enrichment lists belonged to development processes, regulation of phosphorylation, regulation of cellular pathways including metabolism, kinase activity and cellular organization. Real-time PCR confirmed significant increased expression of MMP1, PLAT and ARHGAP22 genes while A2M gene showed decreased expression in treated cells compared to controls. Interestingly, differentially regulated MMP1, PLAT and A2M genes are involved in the extracellular matrix (ECM) remodelling through the fibrinolytic system that is also implicated in embryogenesis, wound healing and angiogenesis. In our model QMR-treated MSC maintained unaltered cell phenotype, viability, proliferation and the ability to differentiate into bone, cartilage and adipose tissue. Microarray analysis may suggest an involvement of QMR treatment in angiogenesis and in tissue regeneration probably through ECM remodelling.

OBJECTIVE

In contrast to prepared natural dentin abutments,little is known concerning factors influencing the retention of fixed prostheses cemented to implant abutments. The aim of this study was to investigate the effect of im-plant abutment height on the retention of single castings cemented to wide and narrow platform implant abutments.

METHODS

Thirty-six parallel-sided abutments (Biohorizon Straight Abutment) of narrow platform (NP) and wide platform (WP) sizes with their analogs were used. In each group of platform size, abutments were prepared with axial wall heights of 5, 4, 3, 2 mm (n=9). On the whole 72 castings were constructed, which incorporated an attachment to allow removal. Castings were cemented to abutments with TempBond®. A uniaxial tensile force was applied to the crown using an Instron machine until cement failure occurred. Analysis of variance of the models were fit to determine the effect of height of abutment of the restorations on the mean tensile strength (α=0.05).

RESULTS

The mean peak removal force for corresponding abutments was significantly different (P < 0.05): (1) with plat-form sizes: WP>> NP; (2) with alteration of axial wall height for NP: 5 mm>> 4 mm>> 3 mm = 2 mm and for WP: 5 mm>> 4 mm = 3 mm = 2 mm.

CONCLUSIONS

The retention of NP cement-retained restorations is influenced by the wall height but not in same manner as WP. Restorations of narrow-platform size with longer abutment exhibited higher tensile resistance to dislodgement.

A total of 215 subjects comprising 95 Chinese, 66 Malays and 54 Indians were investigated for restriction fragment length polymorphisms of the tissue-type plasminogen activator (PLAT) gene at an EcoRI site using the probe ptPA-4352. The phenotypic distribution showed a good agreement with the Hardy-Weinberg equilibrium. The gene frequencies of PLAT*1 were found to be 0.47 in the Chinese, 0.52 in the Malays and 0.41 in South Indians.

Obesity impairs reproductive functions through multiple mechanisms, possibly through disruption of ovarian function. We hypothesized that increased adiposity will lead to a proinflammatory gene signature and upregulation of Egr-1 protein in ovaries from obese (OB; n = 7) compared with lean (LN; n = 10) female Sprague-Dawley rats during the peri-implantation period at 4.5 days postcoitus (dpc). Obesity was induced by overfeeding (40% excess calories for 28 days) via total enteral nutrition prior to mating. OB dams had higher body weight (P < 0.001), greater fat mass (P < 0.001), and reduced lean mass (P < 0.05) and developed metabolic dysfunction with elevated serum lipids, insulin, leptin, and CCL2 (P < 0.05) compared with LN dams. Microarray analyses identified 284 differentially expressed genes between ovaries from LN vs. OB dams (±1.3 fold, P < 0.05). RT-qPCR confirmed a decrease in expression of glucose transporters GLUT4 and GLUT9 and elevation of proinflammatory genes, including CCL2, CXCL10, CXCL11, CCR2, CXCR1, and TNFα in ovaries from OB compared with LN (P < 0.05). Protein levels of PI3K and phosphorylated Akt were significantly decreased (P < 0.05), whereas nuclear levels of Egr-1 (P < 0.05) were increased in OB compared with LN ovaries. Moreover, Egr-1 was localized to granulosa cells, with the highest expression in cumulus cells of preovulatory follicles. mRNA expression of VCAN, AURKB, and PLAT (P < 0.05) correlated with %visceral fat weight (r = 0.51, -0.77, and -0.57, respectively, P ≤ 0.05), suggesting alterations in ovarian function with obesity. In summary, maternal obesity led to an upregulation of inflammatory genes and Egr-1 expression in peri-implantation ovarian tissue and a concurrent downregulation of GLUTs and Akt and PI3K protein levels.

OBJECTIVE

To evaluate the impact of dipyrone administration in the first days of the disease on the severity of dengue infection.

METHODS

Prospective cohort study in adults >> 12 years) with dengue virus infection, confirmed by specific IgM titers in paired samples or isolation of the virus. The patients were enrolled in the first 96 hours of the disease. Basic demographic details, symptoms, drugs received and examination findings were recorded at admittance. A detailed clinical examination and hematocrit determination were done every day by a member of the study team until day 7 of disease. Platelet count was performed at baseline and with the development of spontaneous bleeding or evidence of plasma leakage. The association between dipyrone use in the first 96 hours of disease and the risk of dengue hemorrhagic fever (DHF) was evaluated.

RESULTS

Seven of the 110 patients enrolled developed DHF. At admission, 17 patients had received dipyrone and administration of this drug was not related to the clinical manifestations of dengue, or the use of other medication. Dipyrone was associated with an increased risk of presenting DHF (RR = 7.29; 95% CI: 1.79-29.34; P = 0.0016). Minimum platelet count in the dipyrone group (median: 105,588.2 plat/microl), was significantly smaller than that of the control group (median: 145,698.9 plat/microl): difference = 40,110.69 plat/microl; 95% CI: 1597.36-78,624.02; P = 0.0414.

CONCLUSIONS

Our data suggest that early administration of dipyrone in patients with disease caused by dengue virus is associated with lower platelet counts and an increased risk of developing DHF.