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['During continuous epidural anesthesia with lidocaine, plasma monoethylglycinexylidide (MEGX), an active metabolite of lidocaine, increases continuously. We assessed the effect of epinephrine on the absorption of lidocaine and the accumulation of MEGX during continuous epidural anesthesia in children.', 'Anesthesia was administered as an initial bolus of 5 mg x kg(-1) of 1% lidocaine solution followed by continuous infusion at 2.5 mg x kg(-1) x hr(-1). Patients in the control group (n = 8) received lidocaine alone, while patients in the epinephrine group (n = 8) received lidocaine + epinephrine (5 microg x mL(-1)). Concentrations of lidocaine and its active metabolite, MEGX, were measured in plasma samples obtained after 15 min, 30 min, and one, two, three, four, and five hours of infusion using high-performance liquid chromatography with ultraviolet detection.', 'Plasma lidocaine concentrations were higher in samples from the control group for the first hour; however, after two hours the levels were the same in all samples. Plasma MEGX levels increased continuously in both groups and were significantly higher in the control group samples. The sum of lidocaine + MEGX was higher in the control group for the first two hours but there was no significant difference between groups after three hours.'] |
['Ursodeoxycholic acid prevents gallstone formation in selected patients. The aim of this study was to examine whether decreased concentration and nucleation-promoting activity of various proteins contribute to this beneficial effect.', 'Gallbladder bile of 13 patients with cholesterol gallstones treated with ursodeoxycholic acid (10 mg/kg(-1)/day(-1)) and of 13 untreated patients were compared.', 'Total protein concentration in gallbladder bile (2.8 +/- 0.6 vs. 6.7 +/- 1.3 mg/mL; P=0.008) and concanavalin A-binding fraction (0.16 +/- 0.03 vs. 0.42 +/- 0.07 mg/mL; P=0.003) were strongly decreased by ursodeoxycholic acid therapy. Significant decreases were also found for gallbladder bile alpha1-acid glycoprotein, haptoglobin, immunoglobulin (Ig) A, IgG, gamma-glutamyl transpeptidase, and aminopeptidase N but not for IgM, mucin, or beta-glucuronidase. Decreases were most pronounced for proteins of canalicular membrane origin. Gallbladder bile total protein correlated with cholesterol saturation index (r=0.54; P=0.0047) but not with bile salt hydrophobicity index. Crystallization-promoting activity of the concanavalin A-binding fraction (assessed by nephelometry and microscopic examination) was also significantly decreased by ursodeoxycholic acid.'] |
['Cerebral regional oxygen saturation (rSO(2)) measured with near-infrared spectroscopy (NIRS) has a well-proven clinical utility. A goal-oriented treatment based on the rSO(2) resulted in a significant reduction in major morbidity and in a shortening of postoperative hospital stay in patients undergoing coronary revascularization. In this study, we have compared the values of superior vena cava saturation (ScvO(2)) continuously measured with a Pediasat catheter and the corresponding NIRS rSO(2) values obtained during cardiac operations in pediatric patients.', 'This was a prospective observational study enrolling fifteen pediatric patients (age: 6 days-7 years) undergoing cardiac operations. ScvO(2) data obtained with the Pediasat during the operation were compared with simultaneously recorded NIRS rSO(2) values.', 'One hundred and seventeen matched sets of data were obtained during the operation. ScvO(2) continuously measured with the Pediasat was significantly correlated with the corresponding NIRS rSO(2) values. However, there was a constant positive bias (ScvO(2) values were higher than NIRS rSO(2) values) of 5.6%, with a precision of 10.4%. Time-related percentage changes of NIRS rSO(2) were significantly correlated with the corresponding ScvO(2) percentage changes. A decrease in ScvO(2) is predictive for a decrease in rSO(2) with a sensitivity of 73.7% and a specificity of 85.7%.'] |
['The loss of skeletal muscle mass with aging has been attributed to a decline in muscle fiber number and muscle fiber size.', 'To define to what extent differences in leg muscle cross-sectional area (CSA) between young and elderly men are attributed to differences in muscle fiber size.', 'Quadriceps muscle CSA and type I and type II muscle fiber size were measured in healthy young (n=25; 23 ± 1 y) and older (n=26; 71 ± 1 y) men. Subsequently, the older subjects performed 6 months of resistance type exercise training, after which measurements were repeated. Differences in quadriceps muscle CSA were compared with differences in type I and type II muscle fiber size.', 'Quadriceps CSA was substantially smaller in older versus young men (68 ± 2 vs 80 ± 2 cm(2), respectively; P<0.001). Type II muscle fiber size was substantially smaller in the elderly vs the young (29%; P<0.001), with a tendency of smaller type I muscle fibers (P=0.052). Differences in type II muscle fiber size fully explained differences in quadriceps CSA between groups. Prolonged resistance type exercise training in the elderly increased type II muscle fiber size by 24 ± 8% (P<0.01), explaining 100 ± 3% of the increase in quadriceps muscle CSA (from 68 ± 2 to 74 ± 2 cm(2)).'] |
['The human epidermal growth factor receptor (HER) family consists of four members: ErbB-1 (HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4). These receptors activate numerous downstream pathways in response to extracellular ligands, regulating diverse processes that include differentiation, migration, proliferation, and survival. Alterations in these genes play a role in the development and progression of many human cancers. In gastric carcinomas (GCs), expression of HER1 and HER2 is thought to be a prognostic factor and target of novel biologic agents. The effect of HER3 or HER4 expression in GC has not been sufficiently studied. In this study, we explored the gene and protein expression of the HER family in GC to establish new potential prognostic factors.', 'Immunohistochemistry and fluorescence in situ hybridization were performed in 221 patients with GC using tissue microarray. Correlation between the expression or amplification of HER genes and the clinicopathologic parameters was statistically analyzed.', 'Alterations of members of the HER family were significantly associated with the parameters involved in tumor progression, including depth of tumor invasion, involved lymph nodes, and tumor stage. In addition, HER2 amplification and HER3 expression were significantly related to worse survival.'] |
['A common variant in the FTO gene, rs9939609, associates with body mass index (BMI) in adults and in children aged 7 yr or older.', 'Our aim was to examine the associations of the FTO genotype with BMI, cardiovascular risk factors, energy intake, and leisure-time physical activity in children followed up since infancy.', 'Healthy participants of the STRIP Study, genotyped for rs9939609, were followed from age 7 months (n = 640) to 15 yr (n = 438). The children were randomly assigned to lifestyle intervention and control groups. Height, weight, blood pressure, and serum lipids were measured annually. Food records and physical activity index were obtained at age 15 yr.', 'The FTO genotype did not associate with BMI in children younger than 7 yr of age. From age 7 yr onward, the children homozygous for the A allele had progressively higher BMI than the children with one or two T alleles (P = 0.029 for FTO by age interaction). Furthermore, in longitudinal, BMI Z-score-adjusted analysis, the AA genotype associated with higher systolic and diastolic blood pressure and with elevated serum total and low-density lipoprotein-cholesterol (P = 0.01, P < 0.001, P = 0.05, and P = 0.04 for main effect, respectively). The FTO genotype did not associate with energy intake or physical activity index at age 15. The FTO *Study group interactions were not significant.'] |
['To assess whether deployment of an endograft limb in the external iliac artery (EIA) increases the rate of limb occlusion following endovascular aneurysm repair (EVAR).', 'Interrogation of a prospectively maintained database identified 661 patients (596 men; median age 73 years, range 37-93) with infrarenal abdominal aortic aneurysm who underwent EVAR between 1996 and 2010 using Zenith stent-grafts predominately. Of these, 567 patients [56 (9.9%) women] had both endograft limbs deployed in the CIA (1203 limbs at risk), while 94 patients [9 (9.6%) women] had at least 1 limb in the EIA (22 bilateral; 116 limbs at risk). An adjunctive bare metal stent was used in 8 (9%) limbs deployed in the EIA.', 'There were 31 limb occlusions, all unilateral: 17 (3%) patients in the CIA group had an occluded limb (1% of limbs at risk) vs. 14 (15%) patients in the EIA group (12% of limbs at risk; p<0.0001). The median time to occlusion was 3 months (0-60) in the CIA group and 1 month (0-36) in the EIA group. The majority of occlusions were treated by extra-anatomical revascularization, most often a femorofemoral crossover bypass. No legs were amputated following occlusion of a limb placed in the CIA, but there were 3 amputations in the EIA group (p=0.003).'] |
['The ability of intestinal helminths to manipulate the immune system of their host towards a Th2 response has been proposed to modulate auto-immune and allergic diseases.', 'This initial study investigated the anti-inflammatory potential of S. mansoni and soluble egg antigen (SEA) in a murine model of colitis.', 'Colitis was induced in female NMRI mice by 5% dextran sulfate sodium (DSS) for 7\xa0days, either 9\xa0weeks post-infection with S. mansoni or during treatment with SEA. In addition to clinical signs of colitis, colon histology, immunohistochemistry, and flow cytometry of leukocytes were performed. Colon cytokines were measured using a quantitative real-time technique.', 'Infection with cercariae of S. mansoni attenuated DSS-induced colitis. Clinical symptoms such as weight loss and shortening of colon length were significantly prevented. Histological scores and cell infiltration were affected and expression of pro-inflammatory cytokines in the colons of infected DSS colitis mice was reduced. In contrast, application of SEA failed to improve colitis, even though some findings like earlier manifestation of inflammation and local induction of Th2 cytokines were similar to the effects of cercarial infection.'] |
['SPAK (Ste20p-related proline alanine-rich kinase) phosphorylates and activates NKCC1 (Na-K-2Cl cotransporter) in the presence of another serine/threonine kinase WNK4 (With No lysine (K)). However, whether or not the docking of SPAK to NKCC1 is a requirement for cotransporter activation has not been fully resolved.', 'We mutated both SPAK binding motifs in the amino-terminal tail of NKCC1 and tested the interaction between SPAK and NKCC1 using a semi in vivo yeast two-hybrid assay, (32)P-ATP in vitro phosphorylation assays, and (86)Rb(+) uptake (a K(+) congener) assays in heterologously expressed Xenopus laevis oocytes. We also used site-directed mutagenesis to identify the principle phospho-regulatory threonine residues in the amino-terminal tail of NKCC1.', 'A single SPAK binding motif is necessary for isotonic NKCC1 activation. Mutation of the phenylalanine (F) residue within the motif abrogates binding and function. Phosphorylation of the cotransporter is markedly reduced in the absence of SPAK docking to NKCC1. Truncations of internal regions of the amino-terminus of NKCC1 do not disrupt protein structure enough to affect cotransporter function. Threonine residues (T(206) and T(211)) are both identified as phospho-regulatory sites of NKCC1 function.'] |
['Flavonoids are structurally heterogeneous, polyphenolic compounds present in high concentrations in fruits, vegetables, and other plant-derived foods. Currently, there is growing interest in the therapeutic applications of bioflavonoids for the treatment and prevention of diseases in humans. Myricetin is a naturally occurring flavonoid that is commonly found in tea, berries, fruits, vegetables, and medicinal herbs. Previous studies have shown that myricetin has antioxidant, anti-inflammatory and potent anticancer effects. It was interesting to investigate whether myricetin has the cooperative inhibitory effect combined with 5-fluorouracil on esophageal cancer cells.', 'EC9706 cells were treated with 5-fluorouracil combination with or without myricetin. Colony formation assays, CCK-8 assay and flow cytometry were used to evaluate the chemosensitization activity of myricetin combine with 5-fluorouracil on the cell growth and viability, cell proliferation and apoptosis in vitro. Western blot was engaged to detect changes of Survivin, Cyclin D, Bcl-2, Caspase-3 and P53 protein expression level, which were associated with cells proliferation and apoptosis. Nude mouse tumor xenograft model was built to assessed chemosensitization effect of myricetin combine with 5-fluorouracil in vivo.', 'Compared with the 5-fluorouracil group without myricetin treatment, the groups treated with 5-fluorouracil combine with myricetin showed significantly suppressed cell survival fraction and proliferation, increased the cell apoptosis. Decreased Survivin, Cyclin D, Bcl-2, and increased Caspase-3, P53 expression level were aslo confirmed by western blot in 5-fluorouracil combine with myricetin groups in vitro. And in vivo assay, growth speed of tumor xenografts was significantly decreased in the mice treated with 5-fluorouracil\u2009+\u2009myricetin combiantion group.'] |
['External lumbar drainage (ELD) of CSF is a test to determine the suitability of a shunt for patients with normal pressure hydrocephalus (NPH), but its effect on ventricular volume is not known. This study investigates the effect of 3-day ELD of 500 mL on ventricular size and clinical features in patients with idiopathic NPH.', 'Fifteen patients were investigated in a 1.5-T MRI scanner before and after ELD. Ventricular volume was measured manually. Clinical features involved motor and cognitive functions, testing primarily gait and attention. Reduction in ventricular volume was correlated to total drain volume and clinical parameters. Statistical tests were nonparametric, and p < 0.05 was required for significance.', 'Drain volume was 415 mL (median 470 mL, range 160-510 mL). Ventricular size was reduced in all patients, averaging 3.7 mL (SD 2.2 mL, p < 0.001), which corresponded to a 4.2% contraction. The ratio of volume contraction to drain volume was only 0.9%. Seven patients improved in gait and 6 in attention. Ventricular reduction and total drain volume correlated neither with improvement nor with each other. The 7 patients with the largest drain volumes (close to 500 mL), had ventricular changes varying from 1.3 to 7.5 mL.'] |
['We investigated the interaction between spinally administered bupivacaine and clonidine using an animal model of acute and inflammatory pain. Rats implanted with lumbar intrathecal catheters were injected intrathecally with saline (control), bupivacaine (1 to 100 microg), or clonidine (0.1 to 3 microg) and tested for their responses to thermal stimulation to the tail (tail flick test) and subcutaneous formalin injection into the hindpaw (formalin test). The effects of the combination of bupivacaine and clonidine on both stimuli were tested by isobolographic analysis. General behavior and motor function were examined as side effects. The 50% effective doses of bupivacaine and clonidine were significantly smaller when combined compared with each single drug in both the tail flick test (2.82 and 0.11 microg versus 7.1 and 0.29 microg, respectively) and phase 1 (0.24 and 0.009 microg versus 5.7 and 0.15 microg) and phase 2 (0.31 and 0.012 microg versus 3.2 and 0.16 microg) of the formalin test. Side effects were decreased by the combination. These results suggest a favorable combination of intrathecal bupivacaine and clonidine in the management of acute and inflammatory pain.'] |
['We aimed to investigate serum hepatitis B surface antigen (HBsAg) levels in patients with chronic hepatitis B virus (HBV) infection during peginterferon (PEG-IFN) and entecavir (ETV) monotherapy.', 'HBsAg was quantified (Abbott ARCHITECT) at baseline and during antiviral therapy (weeks 12, 24, 36, 48) in hepatitis B e antigen (HBeAg-) positive patients treated with ETV (n=33) or PEG-IFN (n=61) and in HBeAg-negative patients treated with ETV (n=37) or PEG-IFN (n=69).', 'Within the HBeAg-positive population, patients treated with PEG-IFN tended to have a steeper HBsAg decline than ETV-treated patients (mean decline 0.94 versus 0.38 log IU/ml at week 48, p=0.07 for comparison of the slope of HBsAg decline). The HBsAg decline was larger in those patients who became HBeAg negative, irrespective of the treatment regimen. A decline in HBsAg was confined to ETV-treated patients with elevated baseline alanine aminotransferase (ALT) levels, whereas HBsAg decline was not associated with baseline ALT in patients treated with PEG-IFN. Within the HBeAg-negative population, PEG-IFN induced a significant HBsAg decline, while HBsAg did not decrease in ETV-treated patients (0.56 versus -0.10 log IU/ml, p<0.001). Both in HBeAg-positive and HBeAg-negative patients, the decline in serum HBV DNA was larger in patients who received ETV as compared to patients treated with PEG-IFN.'] |
['Bacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB) challenge was investigated in six tissues.', 'The earliest responses and largest number of affected genes occurred in peripheral blood mononuclear cells (PBMC), spleen, and lung tissues with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney, and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Nine of the 85 genes were subsequently confirmed by RT-PCR in every tissue/organ at 24 h. These 85 transcripts, up-regulated in all tissues, annotated to the interferon (IFN)/antiviral-response and included genes belonging to the DNA/RNA sensing system, DNA damage repair, the immunoproteasome, and the ER/metabolic stress-response and apoptosis pathways. Overall, this shared program was identified as a type I and II interferon (IFN)-response and the promoters of these genes were highly enriched for IFN regulatory matrices. Several genes whose secreted products induce the IFN pathway were up-regulated at early time points in PBMCs, spleen, and/or lung. Furthermore, IFN regulatory factors including Irf1, Irf7 and Irf8, and Zbp1, a DNA sensor/transcription factor that can directly elicit an IFN innate immune response, participated in this host-wide SEB signature.'] |
['Metabolic syndrome has received great attention because it poses a potential cardiovascular hazard, which increases the risk of lower extremity atherosclerosis. However, the relationship between the components of metabolic syndrome and the onset of chronic venous disorder of the lower extremities remains unexplained.', 'This study investigated the characteristics of cardiometabolic risk factors of early chronic venous disorder of the lower extremities in subjects with cardiometabolic risk. The characteristics of risk factors and diabetes-related complications in diabetic patients with early chronic venous disorder of the lower extremities were also investigated. In addition, the association between early chronic venous disorder and atherosclerosis of the lower extremities was analysed. The study examined 782 subjects with cardiometabolic risk factors, including obesity, hypertension, diabetes mellitus and dyslipidaemia. Lower extremity venous function was measured by digital photoplethysmography.', 'Women had a higher prevalence of early chronic venous disorder than did men (p\u2009<\u20090.01). Male subjects with early chronic venous disorder had a higher systolic blood pressure than those with normal venous function (p\u2009<\u20090.01), and female subjects with early chronic venous disorder had a higher fasting plasma glucose level than did controls (p\u2009<\u20090.05). The prevalence of diabetes mellitus is also significantly higher in female patients with early chronic venous disorder (p\u2009=\u20090.000). Diabetic patients with early chronic venous disorder not only had higher fasting plasma glucose and total cholesterol levels but also had more serious macrovascular complications than the control group. The independent risk factors of early chronic venous disorder in female subjects with cardiometabolic risks were age and fasting plasma glucose in men it was only age Women face a two times greater risk than men. The independent risk factors of early chronic venous disorder in diabetic patients were age, gender, HbA1c and triglyceride levels Women had an almost 12 times greater risk of early chronic venous disorder than men. Among the diabetic patients, the prevalence of early chronic venous disorder did not differ by ankle-brachial index.'] |
['Chromosome 3q26-29 is a critical region of genomic amplification in lung squamous cell carcinomas (SCC). Identification of candidate drivers in this region could help uncover new mechanisms in the pathogenesis and potentially new targets in SCC of the lung.', 'We conducted a meta-analysis of seven independent datasets containing a total of 593 human primary SCC samples to identify consensus candidate drivers in 3q26-29 amplicon. Through integrating protein-protein interaction network information, we further filtered for candidates that may function together in a network. Computationally predicted candidates were validated using RNA interference (RNAi) knockdown and cell viability assays. Clinical relevance of the experimentally supported drivers was evaluated in an independent cohort of 52 lung SCC patients using survival analysis.', 'The meta-analysis identified 20 consensus candidates, among which four (SENP2, DCUN1D1, DVL3, and UBXN7) are involved in a small protein-protein interaction network. Knocking down any of the four proteins led to cell growth inhibition of the 3q26-29-amplified SCC. Moreover, knocking down of SENP2 resulted in the most significant cell growth inhibition and downregulation of DCUN1D1 and DVL3. Importantly, a gene expression signature composed of SENP2, DCUN1D1, and DVL3 stratified patients into subgroups with different response to adjuvant chemotherapy.'] |
['The transport of gametes as well as the zygote is facilitated by motile cilia lining the inside of the fallopian tube. Progesterone reduces the ciliary beat frequency within 30\xa0minutes in both cows and mice. This rapid reduction suggest the involvement of a non-genomic signaling mechanism, although it is not known which receptors that are involved. Here we investigated the possible involvement of the classical progesterone receptor in this process.', 'The ciliary beat frequency of mice fallopian tube was measured ex vivo using an inverted bright field microscope and a high speed camera. The effects of the agonists progesterone and promegestone and an antagonist, mifeprestone, were investigated in wildtype mice. The effect of progesterone was also investigated in mice lacking the classical progesterone receptor.', 'Progesterone, as well as the more specific PR agonist promegestone, significantly reduced the CBF at concentrations of 10-100 nanomolar within 10-30\xa0minutes. In the absence of progesterone, the PR antagonist mifeprestone had no effect on the ciliary beat frequency at a concentration of 1 micromolar. When ciliated cells were pre-incubated with 1 micromolar mifeprestone, addition of progesterone did not reduce the ciliary beat frequency. Accordingly, in ciliated cells from mice not expressing the classical progesterone receptor, exposure to 100 nanomolar progesterone did not reduce the ciliary beat frequency.'] |
['Xenorhabdus bacteria engage in a beneficial symbiosis with Steinernema nematodes, in part by providing activities that help kill and degrade insect hosts for nutrition. Xenorhabdus strains (members of a single species) can display wide variation in host-interaction phenotypes and genetic potential indicating that strains may differ in their encoded symbiosis factors, including secreted metabolites.', 'To discern strain-level variation among symbiosis factors, and facilitate the identification of novel compounds, we performed a comparative analysis of the genomes of 10 Xenorhabdus bovienii bacterial strains.', 'The analyzed X. bovienii draft genomes are broadly similar in structure (e.g. size, GC content, number of coding sequences). Genome content analysis revealed that general classes of putative host-microbe interaction functions, such as secretion systems and toxin classes, were identified in all bacterial strains. In contrast, we observed diversity of individual genes within families (e.g. non-ribosomal peptide synthetase clusters and insecticidal toxin components), indicating the specific molecules secreted by each strain can vary. Additionally, phenotypic analysis indicates that regulation of activities (e.g. enzymes and motility) differs among strains.'] |
["Peripheral vestibular hypofunction is a major cause of dizziness. When complicated with postural imbalance, this condition can lead to an increased incidence of falls. In traditional clinical practice, gaze stabilization exercise is commonly used to rehabilitate patients. In this study, we established a computer-aided vestibular rehabilitation system by coupling infrared LEDs to an infrared receiver. This system enabled the subjects' head-turning actions to be quantified, and the training was performed using vestibular exercise combined with computer games and interactive video games that simulate daily life activities.", 'Three unilateral and one bilateral vestibular hypofunction patients volunteered to participate in this study. The participants received 30 minutes of computer-aided vestibular rehabilitation training 2 days per week for 6 weeks. Pre-training and post-training assessments were completed, and a follow-up assessment was completed 1 month after the end of the training period.', 'After 6 weeks of training, significant improvements in balance and dynamic visual acuity (DVA) were observed in the four participants. Self-reports of dizziness, anxiety and depressed mood all decreased significantly. Significant improvements in self-confidence and physical performance were also observed. The effectiveness of this training was maintained for at least 1 month after the end of the training period.'] |
['Previously, we demonstrated that glucocorticoid (GC) treatment of asthmatic patients resulted in decreasing frequencies of monocyte subsets expressing CD16 and capable of releasing TNF-α. Here, we wished to analyze whether the active form of vitamin D, i.e. vitamin D3, referred to as 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can exert GC-like proapoptotic effects on CD16-positive monocytes and thus decrease the proinflammatory potential of these cells. Finally, we set out to investigate whether the addition of 1,25-(OH)2D3 would facilitate the use of lower doses of GC without decreasing their anti-inflammatory properties.', 'Peripheral blood mononuclear cells collected from healthy individuals and asthmatic patients were cultured with 1,25-(OH)2D3 and/or varying doses of GC in the presence or absence of caspase inhibition. The cells were either directly stained for extracellular markers or prestimulated with lipopolysaccharide for the assessment of intracellular cytokine production and then analyzed by flow cytometry.', 'We found that 1,25-(OH)2D3 alone (and in combination with GC) decreased the frequency of CD14++CD16+ and CD14+CD16++ monocytes from asthmatic patients and significantly diminished TNF-α production by the monocytes. With regard to the CD14+CD16++ subset, the monocyte-depleting effects of 1,25-(OH)2D3 were abrogated in the presence of pan-caspase inhibitor, suggesting a proapoptotic mechanism of 1,25-(OH)2D3 action. Interestingly, we found that a combined treatment of 1,25-(OH)2D3 and GC allowed for a 5-fold reduction of the GC dose while maintaining their anti-inflammatory effects.'] |
['Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) often provide dramatic responses in lung cancer patients with somatic EGFR mutation. However, acquired resistance to the drugs usually emerges within a few years. EGFR T790M secondary mutation, MET gene amplification, and transformation to small cell lung cancer are well-validated mechanisms that underlie acquisition of resistance to EGFR-TKIs. In addition, many molecular aberrations have been reported as candidates for mechanisms of acquired resistance to EGFR-TKIs. Amplification of the CRKL gene was reportedly observed in 1 of 11 lung cancer patients with EGFR mutations who acquired resistance to EGFR-TKI. This study is the first report, to our knowledge, that validated the role of CRKL gene amplification as a mechanism for acquisition of resistance to EGFR-TKIs.', 'We analyzed CRKL gene copy numbers, using a quantitative real-time PCR method, in 2 in vitro acquired-resistance cell-line models: 11 clinical samples from patients who developed acquired resistance to EGFR-TKIs, and 39 tumor specimens obtained from 7 autopsy patients whose cancers acquired resistance to EGFR-TKIs. Mutational status of EGFR codon 790 and copy numbers for the MET gene were also determined.'] |
['Monascus Adlay (MA) prepared from fungal fermentation of Monascus purpureus inoculating with cooked adlay contains high content of monakolin K (MK) and phenolic compounds. We explored whether MA and MK improve FeCl3-induced arterial thrombosis in rats.', 'The rats were divided into control, FeCl3-treated rat carotid artery occlusion (TTO), TTO determined with one-week MA, and TTO determined with one-week MK. We compared MA or MK effects on oxidative stress by chemiluminescence amplification and immunohistochemistry, TTO by a transonic system, NFκB, ICAM-1, endoplasmic reticulum stress CHOP and Nrf2 signaling by western blotting.', 'MA or MK efficiently depressed O2-, H2O2 and HOCl levels, platelet activation and aggregation and H2O2-enhanced ICAM-1 and VCAM-1 expression in the endothelial cells. FeCl3 significantly increased NFκB p65, 3-nitrotyrosine, CHOP and ICAM-1 expression, and decreased nuclear Nrf2 translocation and induces arterial thrombus formation. MA or MK pretreatment significantly elongated the level of FeCl3-induced TTO compared to TTO group, significantly decreased proinflammatory NF-κB/ICAM-1 signaling, endoplasmic reticulum stress CHOP expression and decreased thrombotic area. MA or MK significantly preserved nuclear Nrf2 translocation. MA and MK exerted a similar protective effect in attenuating thrombus formation.'] |
['We compared the association between economic status and the prevalence of diabetes mellitus (DM) using large nationwide datasets covering the previous 10 years in Korea.', 'We analyzed the association between economic status and DM using Korean National Health and Nutrition Examination Survey (KNHANES) data from 2001 to 2010 weighted to represent the Korean population between 30 and 59 years of age. The economic status of participants was classified into quartiles according to monthly family income with an equivalence scale.', 'In men, the prevalence of diabetes in the lowest income quartile (Q1) was significantly higher than that in the other quartiles in 2008 (age and body mass index-adjusted odds ratio [OR], 1.846; 95% confidence interval [CI], 1.126 to 3.027; P=0.015), 2009 (OR, 1.706; 95% CI, 1.094 to 2.661; P=0.019), and 2010 (OR, 1.560; 95% CI, 1.024 to 2.377; P=0.039) but not in 2001 or 2005. The data indicated that classification in the lowest economic status was an independent risk factor for diabetes even after adjusting for abdominal obesity, dyslipidemia, hypertension and education level in men of KNHANES 2008 to 2010. Although economic status was significantly associated with abdominal obesity, hypertriglyceridemia, and hypertension in women (P<0.001), there was no significant association between economic status and DM in women.'] |
['To assess the effect of media opacities on thickness measurements of the peripapillary retinal nerve fibre layer (pRNFL) and macular inner retinal layer (mIRL) performed with spectral-domain optical coherence tomography (SD-OCT) using a set of filters with known optical density.', 'Spectral-domain optical coherence tomography volume scans of the optic disc and the macular area were performed in 18 healthy volunteers, using Topcon-3DOCT-1000 Mark II. A set of five filters with optical density ranging from 0.04 to 0.69 was used. The correlation was calculated between the percentage change in thickness measurements (%ΔpRNFL and %ΔmIRL) and the change in optical density. All scans and measurements were performed in duplicate by one operator.', "Eighteen right eyes of 18 healthy volunteers were included in this study. Percentage decrease in pRNFL and mIRL thickness correlated with change in optical density (Spearman's rho r = 0.82; p < 0.001 and r = 0.89; p < 0.001, respectively). The measured decrease in pRNFL thickness differed from the decrease in mIRL thickness, not only between individuals, but also within the same individual."] |
["Infliximab is a monoclonal anti-TNF-α antibody that is used therapeutically to treat Crohn's disease (CD). High levels of pro-inflammatory cytokines, especially TNF-α, have been observed in the gastrointestinal tract of CD patients and were associated with alterations in the mesenteric adipose tissue, which also contributed to the high levels of adipokine release. The authors used a rat model of colitis that produces mesenteric adipose tissue alterations that are associated with intestinal inflammation to study the effects that infliximab treatment has on adipokine production, morphological alterations in adipose tissue and intestinal inflammation.", 'The ability of infliximab to neutralize rat TNF-α was evaluated in vitro using U937 cells. Colitis was induced by repeated intracolonic trinitrobenzene sulfonic acid instillations and was evaluated by macroscopic score, histopathological analysis, myeloperoxidase activity, TNF-α and IL-10 expression as well as iNOS (inducible NO synthase) expression and JNK phosphorylation in colon samples. The alterations in adipose tissue were assessed by TNF-α, IL-10, leptin, adiponectin and resistin levels as well as adipocyte size and peroxisome proliferator-activated receptor (PPAR)-γ expression.', 'Infliximab treatment controlled intestinal inflammation, which reduced lesions and neutrophil infiltration. Inflammatory markers, such as iNOS expression and JNK phosphorylation, were also reduced. In mesenteric adipose tissue, infliximab increased the production of IL-10 and resistin, which was associated with the restoration of adipocyte morphology and PPAR-γ expression.'] |
['Texture analysis has been applied to medical images to assist in tumor tissue classification and characterization. In this study, we obtained textural features from parametric (relative CBV) maps of dynamic susceptibility contrast-enhanced MR images in glioblastoma and assessed their relationship with patient survival.', 'MR perfusion data of 24 patients with glioblastoma from The Cancer Genome Atlas were analyzed in this study. One- and 2D texture feature ratios and kinetic textural features based on relative CBV values in the contrast-enhancing and nonenhancing lesions of the tumor were obtained. Receiver operating characteristic, Kaplan-Meier, and multivariate Cox proportional hazards regression analyses were used to assess the relationship between texture feature ratios and overall survival.', 'Several feature ratios are capable of stratifying survival in a statistically significant manner. These feature ratios correspond to homogeneity (P = .008, based on the log-rank test), angular second moment (P = .003), inverse difference moment (P = .013), and entropy (P = .008). Multivariate Cox proportional hazards regression analysis showed that homogeneity, angular second moment, inverse difference moment, and entropy from the contrast-enhancing lesion were significantly associated with overall survival. For the nonenhancing lesion, skewness and variance ratios of relative CBV texture were associated with overall survival in a statistically significant manner. For the kinetic texture analysis, the Haralick correlation feature showed a P value close to .05.'] |
['Tumor-associated microRNAs have been detected in cancer, though whether plasma microRNA-155 (miR-155) could be a potential biomarker for laryngeal squamous cell carcinoma (LSCC) prognosis is unclear. We aimed to determine how miR-155 can be used to predict the clinical characteristics of patients with LSCC and correctly diagnose them.', 'We collected tissue samples and peripheral blood samples before and after treatment from 280 LSCC cases and 560 controls. Real-time quantitative reverse transcription PCR was employed in this study to compare the relative expression of miR-155.', 'A total of 280 LSCC patients and 560 age- and sex-matched controls were included in the study. The miR-155 level was more up-regulated in LSCC tissue than in the non-tumor tissues (13.6 ± 2.4 vs. 3.1 ± 0.80, p<0.001). Additionally, a significantly higher miR-155 level in plasma samples from LSCC patients than in those of the controls (8.9 ± 1.25 vs. 1.8 ± 0.8, p<0.001) was reported. Tissue miR-155 showed an area under the curve (AUC) of 0.933, with a sensitivity of 82.6% and a specificity of 89.2%. The AUC for plasma miR-155 was 0.757, with a sensitivity of 58.4% and a specificity of 69.5%. When early LSCC in TNM I stage was considered, tissue miR-155 showed an area under the curve of 0.804, with a sensitivity of 85.2% and a specificity of 87.3%.'] |
['Medial knee osteoarthritis (OA) is characterized by pain and associated with abnormal knee moments during walking. The relationship between knee OA pain and gait changes remains to be clarified, and a better understanding of this link could advance the treatment and prevention of disease progression. This study investigated changes in knee moments during walking following experimental knee pain in healthy volunteers, and whether these changes replicated the joint moments observed in medial knee OA patients.', 'In a crossover study, 34 healthy subjects were tested on 3 different days; gait analyses were conducted before, during, and after pain induced by hypertonic saline injections (0.75 ml) into the infrapatellar fat pad. Isotonic saline and sham injections were used as control conditions. Peak moments in frontal and sagittal planes were analyzed. The results were compared with data from 161 medial knee OA patients. The patients were divided into less severe OA and severe OA categories, which was based on radiographic disease severity of the medial compartment.', 'Experimental knee pain led to reduced peak moments in the frontal and sagittal planes in the healthy subjects, which were similar to the patterns observed in less severe OA patients while walking at the same speed.'] |
['Glucagon-like peptide 1 (GLP-1) is a gut-brain hormone that regulates food intake, energy metabolism, and cardiovascular functions. In the brain, through a currently unknown molecular mechanism, it simultaneously reduces femoral artery blood flow and muscle glucose uptake. By analogy to pancreatic β-cells where GLP-1 activates protein kinase C (PKC) to stimulate insulin secretion, we postulated that PKC enzymes would be molecular targets of brain GLP-1 signaling that regulate metabolic and vascular function.', 'We used both genetic and pharmacological approaches to investigate the role of PKC isoforms in brain GLP-1 signaling in the conscious, free-moving mouse simultaneous with metabolic and vascular measurements.', 'In normal wild-type (WT) mouse brain, the GLP-1 receptor (GLP-1R) agonist exendin-4 selectively promotes translocation of PKC-δ (but not -βII, -α, or -ε) to the plasma membrane. This translocation is blocked in Glp1r(-/-) mice and in WT mice infused in the brain with exendin-9, an antagonist of the GLP-1R. This mechanism coordinates both blood flow in the femoral artery and whole-body insulin sensitivity. Consequently, in hyperglycemic, high-fat diet-fed diabetic mice, hypothalamic PKC-δ activity was increased and its pharmacological inhibition improved both insulin-sensitive metabolic and vascular phenotypes.'] |
['Identifying susceptibility genes for endophenotypes by studying analogous behaviors across species is an important strategy for understanding the pathophysiology underlying psychiatric disorders. This approach provides novel biological pathways plus validated animal models critical for selective drug development. One such endophenotype is avoidance behavior.', 'In the present study, novel automated registration methods for longitudinal behavioral assessment in home cages are used to screen a panel of recently generated mouse chromosome substitution strains that are very powerful in quantitative trait loci (QTL) detection of complex traits. In this way, we identified chromosomes regulating avoidance behavior (increased sheltering preference) independent of motor activity levels (horizontal distance moved). Genetic information from the mouse QTL-interval was integrated with that from the homologous human linkage region for a mood disorder.', 'We genetically mapped a QTL for avoidance behavior on mouse chromosome 15, homologous with a human genome region (8q24) linked to bipolar disorder. Integrating the syntenic mouse QTL-interval with genotypes of 1868 BPD cases versus 14,311 control subjects revealed two associated genes (ADCY8 and KCNQ3). Adenylyl cyclase 8 (Adcy8) was differentially expressed in specific brain regions of mouse strains that differ in avoidance behavior levels. Finally, we showed that chronic infusion of the human mood stabilizer carbamazepine (that acts via adenylyl cyclase activity) significantly reduced mouse avoidance behavior, providing a further link between human mood disorders and this mouse home cage behavior.'] |
['CD43 is a transmembrane glycoprotein expressed in different hematopoietic cells, including some subsets of B lymphocytes. About a quarter of diffuse large B-cell lymphomas (DLBCLs) express CD43, but its prognostic significance is unknown.', 'We analyzed the prognostic effect of immunohistochemically determined CD43 expression in 119 patients with newly diagnosed DLBCL. All were treated with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone)-like chemotherapy, 57 without and 62 with rituximab.', 'A total of 31 DLBCL cases (26%) expressed CD43. Patients with CD43+ and CD43- lymphomas did not differ regarding sex, International Prognostic Index (IPI) factors and score, rituximab treatment, presence of bulky disease, or germinal center subtype. Median follow-up was 45 months. Patients with CD43+ DLBCL had significantly lower complete response rates (59% vs. 80%; P = .019), 2-year event-free survival (EFS) rates (34% vs. 64%; P = .003), and overall survival (OS) rates (45% vs. 76%; P = .002). The prognostic significance of CD43 expression was retained in multivariate analysis (relative risk [RR] 2.04; P = .013 for EFS; RR 2.17; P = .016 for OS). In subgroup analysis, the effect of CD43 expression was significant in patients treated with rituximab and those with low IPI, whereas it was not reached in patients treated without rituximab. The effect was not observed in patients with high IPI.'] |
['The aim of this study was to define the relationship between physical activity and the magnitude of the percentage fall in blood pressure at night (nocturnal dip).', 'We simultaneously monitored 24-h ambulatory blood pressure and measured physical activity by actigraphy in 434 patients. Blood pressure was measured every 20 min; the actigraph integrated an activity score every 10 s. Mean daytime and night-time activity were calculated from mean scores for the 15 min preceding each blood pressure measurement. Nocturnal dip in systolic and diastolic blood pressure (SBP and DBP) were regressed on mean (log-transformed) daytime activity. Mean night-time activity, age, gender, smoking status, body mass index (BMI) and clinic blood pressure were added into a multiple linear regression.', 'The patient group was heterogeneous in age, gender and mean 24-h blood pressure. Mean daytime activity level was significantly and positively associated with the magnitude of the nocturnal dip in both SBP and DBP. Increased night-time activity was significantly associated with a smaller nocturnal dip. Older patients had a smaller nocturnal dip per log unit daytime activity. Nocturnal dip in SBP was greater in males, and smaller in those taking antihypertensive medications. Smoking, BMI and clinical blood pressure level were not associated with the extent of the nocturnal dip after adjustment for other factors.'] |
['Endotoxin and its purified derivative LPS are important contaminants of both domestic and occupational environments that have been related to airway diseases. A body of data suggests that there is considerable interindividual variability in LPS sensitivity.', 'The aim of the study was to relate the individual clinical responses to inhaled LPS with the inflammatory process and the atopic status.', 'Fifteen healthy subjects were challenged each week by inhalation with saline solution or LPS (0.5, 5, or 50 microg). The systemic response was defined by the increase in body temperature, blood neutrophilia, acute-phase proteins (C-reactive protein and LPS-binding protein [LBP]), and E-selectin. The LPS-induced airway response was defined as the increase in airway responsiveness and related to the cell count and concentration of TNF-alpha, myeloperoxidase, and eosinophil cationic protein in induced sputum. The atopic status was defined as an increase in IgE or a positive skin prick test result.', 'Subjects (n = 7) with a significant increase in body temperature had a larger increase in the systemic inflammatory response (blood neutrophilia; P <.01) and in blood concentrations of C-reactive protein (P <.02) and LBP (P <.01). Subjects with a significant increase in airway responsiveness (n = 8) had an increase in the sputum concentration of eosinophil cationic protein (P <.01). The amplitude of the systemic response (increase in body temperature [P <.001], blood neutrophilia [P <.02], and rise in LBP [P <.05] and decrease in FEV(1) [P <.01]) were inversely associated with the atopic status, suggesting a link between atopy and LPS responsiveness.'] |
['Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerosis. However, the degree of endothelial dysfunction and its relationship to traditional and novel cardiovascular risk factors have not been examined in SLE.', 'In a case-control design, 35 patients with clinically stable SLE and 35 control subjects matched for age, sex, body mass index and smoking status were studied. Arterial elasticity, lipid profile, homocysteine, measures of inflammation and oxidative stress were determined.', 'Among traditional vascular risk factors, there was a nonsignificant trend towards lower blood pressure in the control subjects, whereas low-density lipoprotein (LDL) cholesterol levels were significantly lower in the SLE group (2.5 vs 3.3 mmol/L, P < 0.001). Patients with SLE had significantly lower small artery elasticity (SAE; 4.9 vs 7.0 ml/mmHg x 100, P < 0.001) and higher plasma homocysteine (11.4 vs 8.3 mmol/L, P = 0.002) than control subjects. Levels of serum sVCAM-1 (614 vs 494 ng/mL, P = 0.002), oxidized LDL (144 vs 97, P < 0.001) and CD40 ligand (4385 vs 1373 pg/ml, P = 0.001) were significantly higher in SLE. Oxidized LDL levels, older age at SLE diagnosis and higher disease damage scores correlated inversely with SAE but not traditional risk factors.'] |
['A carbohydrate (CHO) drink given preoperatively changes the fasted state into a fed state. The ESPEN guidelines for perioperative care include preoperative CHO loading and re-establishment of oral feeding as early as possible after surgery. An intestinal ischaemia reperfusion (IR) animal model was used to investigate whether preoperative CHO loading increases spontaneous postoperative food intake, intestinal barrier function and the catabolic response.', 'Male Wistar rats (n = 65) were subjected to 16 h fasting with ad libitum water and: A) sham laparotomy (Sham fasted, n = 24); B) intestinal ischaemia (IR fasted, n = 27); and C) intestinal ischaemia with preoperatively access to a CHO drink (IR CHO, n = 14). Spontaneous food intake, intestinal barrier function, insulin sensitivity, intestinal motility and plasma amino acids were measured after surgery.', 'The IR CHO animals started eating significantly earlier and also ate significantly more than the IR fasted animals. Furthermore, preoperative CHO loading improved the intestinal barrier function, functional enterocyte metabolic mass measured by citrulline and reduced muscle protein catabolism, as indicated by normalization of the biomarker 3-methylhistidine.'] |
['Topical adverse events caused by inhaled corticosteroids (ICS) are suspected to be more common in females. Although gargling or mouth washing after inhalation is recommended as the gold standard for preventing adverse events due to ICS, the preventive effects of this method have not been confirmed in real-world studies. This study aimed to examine the association between gargling or mouth washing and the incidence of topical adverse symptoms in males and females in daily practice.', 'We analyzed a subpopulation of participants in the Drug Event Monitoring (DEM) project of the Japan Pharmaceutical Association. An anonymous survey was performed in February 2010, to assess the self-perception of topical adverse symptoms during ICS use by conducting interviews of pharmacists using structured questionnaires.', 'A total of 412 males and 480 females were included. The patients used a dry-powder inhaler (DPI) (71.2%), pressurized meter-dose inhaler (pMDI) with (7.5%) or without (16.6%) a spacer or inhalation solution (4.7%) as the delivery device. Topical adverse symptoms occurring after previous prescriptions were reported by 41 (4.6%) subjects. The common symptoms were hoarseness, stomatitis and dry mouth (1.3%, 1.1% and 1.1%, respectively). In the multiple regression model, the presence of symptoms was found to be significantly associated with the absence of gargling or mouth washing after inhalation [adjusted odds ratio (OR): 3.75, 95% confidence interval (95%CI): 1.33-10.59, p\u2009=\u20090.012]. When stratified by gender, the absence of gargling or mouth washing was identified to be a risk factor in females only (OR: 4.32, 95%CI: 1.11-16.87, p\u2009=\u20090.035) and not in males (OR: 3.26, 95%CI: 0.65-16.33, p\u2009=\u20090.151). Furthermore, the association between the absence of gargling or mouth washing and the incidence of topical adverse symptoms was significant in the patients using DPI (OR: 4.85, 95%CI: 1.66-14.14, p\u2009=\u20090.004), but not in those using the other devices.'] |
['Calcification of hypertrophic chondrocytes is the final step in the differentiation of growth plates, although the precise mechanism is not known. We have established two growth plate-derived chondrocyte cell lines, MMR14 and MMR17, from p53-/- mice (Nakamata T, Aoyama T, Okamoto T, Hosaka T, Nishijo K, Nakayama T, et al. In vitro demonstration of cell-to-cell interaction in growth plate cartilage using chondrocytes established from p53-/- mice. J Bone Miner Res 2003;18:97-107). Prolonged in vitro culture produced calcified nodules in MMR14, but not in MMR17. Factors responsible for the difference in calcification between the two cell lines may also be involved in the physiological calcification in growth plate.', 'Gene expression profiles of MMR14 and MMR17 were compared using a cDNA microarray to identify candidate genes involved in the calcification process.', 'Forty-five genes were identified as upregulated in MMR14, including the cadherin-11 (Cdh-11) gene. The expression of Cdh-11 in MMR14 was detected in cell-cell junctions, while no expression was observed in MMR17. Primary cultured chondrocytes from growth plate (GC) also expressed the Cdh-11, and the staining of Cdh-11 was observed in the late hypertrophic zone of growth plate. Cell aggregation assays showed that chondrocytes required Ca2+ to form nodules, and knockdown of the Cdh-11 gene expression using short interfering RNA inhibited the formation of calcified nodules in MMR14. The introduction of Cdh-11 into MMR17 failed to produce calcified nodules indicating that Cdh-11 is one, but not the sole, factor responsible for the production of calcified nodules.'] |
['We have previously demonstrated that chronic treatment with the hexapeptide angiotensin (Ang) IV significantly improved endothelium-dependent vasorelaxation in isolated aorta obtained from young adult apolipoprotein E-deficient (ApoE(-/-)) mice. The current study aimed to investigate whether this effect is evident using ApoE(-/-) mice with established atheroma.', 'ApoE(-/-) mice fed a high-fat diet for a period of 26 weeks displayed significantly impaired endothelial function compared to wild-type mice. Importantly, 2-week treatment with Ang IV, significantly improved endothelial function despite the abundance of atherosclerotic lesions. Endothelial nitric oxide synthase immunoreactivity was significantly increased, whereas superoxide levels assessed using dihydroethidium staining were concomitantly decreased, in aortic cross-sections taken from Ang IV treated mice compared with vehicle treated ApoE(-/-) mice. [(125)I] Ang IV autoradiographic analysis revealed an upregulation of AT(4)Rs in ApoE(-/-) mice fed a high-fat diet for 26 weeks compared to 8 weeks. Co-treatment with an AT(4)R antagonist, divalinal-Ang IV or an AT(2)R antagonist, PD123319 significantly abrogated these Ang IV-induced vasoprotective effects.'] |
The analyses presented here demonstrate that while general mechanisms by which X. bovienii bacterial strains interact with their invertebrate hosts are similar, the specific molecules mediating these interactions differ. Our data support that adaptation of individual bacterial strains to distinct hosts or niches has occurred. For example, diverse metabolic profiles among bacterial symbionts may have been selected by dissimilarities in nutritional requirements of their different nematode hosts. Similarly, factors involved in parasitism (e.g. immune suppression and microbial competition factors), likely differ based on evolution in response to naturally encountered organisms, such as insect hosts, competitors, predators or pathogens. This study provides insight into effectors of a symbiotic lifestyle, and also highlights that when mining Xenorhabdus species for novel natural products, including antibiotics and insecticidal toxins, analysis of multiple bacterial strains likely will increase the potential for the discovery of novel molecules. |
['An increase of matrix metalloproteinase-2 (MMP-2) has been found to improve outflow through the uveoscleral pathway. This experiment was designed to test whether reduction of inhibitor of nuclear factor kappa B alpha (IkappaBalpha) levels could enhance MMP-2 expression in human ciliary muscle (HCM) cells in vitro.', 'The small interfering RNA (siRNA) targeting inhibitor of nuclear factor kappa B (IkappaBalpha) was transfected into HCM cells. The mRNA and protein levels of IkappaBalpha, nuclear factor-kappa B (NF-kappaB)p65, MMP-2, tissue inhibitor of metalloproteinase-2 (TIMP-2), and membrane-type 1 matrix metalloproteinase (MT1-MMP) in HCM cells were examined 24 h, 48 h, and 72 h after IkappaBalpha siRNA transfection by real-time reverse transcription polymerase chain reaction (RT-PCR) and western blot. The activation of NF-kappaBp65 was determined through the translocation of NF-kappaBp65 by fluorescence microscope. Gelatin zymography was used to detect the secretion and activity of MMP-2.', "Real-time RT-PCR and western blot showed that transfection of IkappaBalpha siRNA led to gradual downregulation of IkappaBalpha and TIMP-2 both at the mRNA and protein level after 24 h, 48 h and 72 h. The IkappaBalpha and TIMP-2 mRNA levels decreased 92.7%+/-1.6% and 70.3%+/-13.1%, respectively, and the protein levels were reduced 87.3%+/-2.0% and 62.9%+/-0.8% (p<0.01), respectively, when compared to the control 72 h after siRNA transfection. Conversely, the MMP-2 and MT1-MMP mRNA and protein levels increased in the time-dependent manner after IkappaBalpha siRNA transfection. The MMP-2 and MT1-MMP mRNA levels increased 178%+/-4.6% and 165%+/-8.2%, respectively, while protein levels were raised to 162%+/-3.7% and 157.6%+/-5.7% (p<0.01), respectively, when compared to the control 72 h after IkappaBalpha siRNA transfection. Although no obvious changes were seen in either mRNA or protein levels of total NF-kappaBp65 (p>0.05), the protein level of NF-kappaBp65 increased dramatically in the nucleus as revealed by western blot and fluorescence staining 24 h, 48 h, and 72 h after IkappaBalpha siRNA transfection. Moreover, gelatin zymography indicated that the secretion and activity of MMP-2 in treated cells were higher than those in the control cells. The maximum increases of pro-MMP-2 and active-MMP-2 were 172%+/-15% and 151%+/-14% (p<0.01), respectively, when compared to the control at the experiment's conclusion 72 h after siRNA transfection."] |
['To evaluate the relationship between the nutritional habits of university students with health parameters related to cardiovascular risk.', 'Three hundred and twelve students (180 females and 132 males; mean age 21.1 +/- 2.8 years) attending King Saud University, Riyadh, KSA were randomly selected from the university register and invited to participate in the study during 2008-2009. Students who consented to participate completed a self-reported questionnaire including: nutritional screen, health habits, and lifestyle practice. Daily food consumption was recorded, and nutritional analysis was performed. Blood pressure (BP) was also measured.', 'A quarter of students was found to be overweight (21%) or obese (6.5%). The percentage of overweight and obese male students was 23% and 7% compared with female students who were 19% overweight and 6% obese. There was a positive correlation between fat consumption and BMI as well as BP in both genders, between economical status and BMI (p=0.05), and between salty food and BP (p=0.05). There was a negative correlation between consumption of fiber, grains, vegetables, fruits, beans, and BMI as well as BP in both genders (p=0.05).'] |
['To investigate the role of angiotensin converting enzyme (ACE) inhibition in bradykinin-mediated modulation of noradrenaline release in human and rat atrium.', 'Human and rat atrial slices were incubated with [3H]-noradrenaline, superfused with Krebs-Henseleit solution and stimulated electrically at 5 Hz. The stimulation-induced outflow of radioactivity was taken as an index of endogenous noradrenaline release.', 'In the absence of ACE inhibition 0.01-1 micromol/l bradykinin failed to alter the release of noradrenaline in human atrium. In contrast, 0.001-0.1 micromol/l bradykinin enhanced the release of noradrenaline in rat atrium. In the presence of 3 micromol/l of the ACE inhibitor captopril, however, bradykinin significantly enhanced the release of noradrenaline in human atrium. The bradykinin B1-receptor agonist (Des-Arg9)-bradykinin (0.01-1 micromol/l) had no effect on the release of noradrenaline in human atrium both in the absence and in the presence of 3 micromol/l captopril. Captopril (3 micromol/l) potentiated the facilitatory effect of bradykinin in rat atrium. The selective bradykinin B2-receptor antagonist D-Arg[Hyp3,Thi5, D-Tic7,Oic8]-bradykinin (Hoe 140, 0.3 micromol/l) and the cyclo-oxygenase inhibitor indomethacin (10 micromol/l) reduced the facilitatory effect of bradykinin significantly in the presence of captopril in rat and human atrium. Prostaglandin F2alpha (0.1 micromol/l), prostaglandin E2 (0.3 micromol/l) and the thromboxane A2 receptor agonist U-46 619 (0.1 micromol/l) enhanced the release of noradrenaline in human atria, whereas 0.1 micromol/l prostaglandin I2 had no effect.'] |
['In Fontan candidates, we have recently been aggressively performing the Damus-Kaye-Stansel procedure (DKS) to prevent increased afterload on the systemic ventricle. The present study investigated the efficacy of the DKS procedure in terms of the ventricular function following a Fontan operation.', 'Patients undergoing a Fontan operation were divided into three groups: DKS performed at the time of the bidirectional Glenn or Fontan operation (DKS group, n = 25); DKS not performed at any stage due to mild pulmonary stenosis (PS) (PS group, n = 23) and DKS not performed due to pulmonary atresia (PA) or severe PS (PA group, n = 24). Ventricular function, afterload on the systemic ventricle and atrioventricular valve regurgitation were compared between groups.', 'Cardiac catheterization before a Glenn or Fontan operation and at 1-year following the Fontan revealed significantly decreased ventricular end-diastolic pressure in the DKS group. The ventricular ejection fraction was significantly deteriorated in the PS group. Effective arterial elastance, as an index of total ventricular afterload, was increased after a Fontan in all groups, with a substantial increase in the PS group. As an index of ventricular mechanical efficiency, ventriculoarterial coupling was significantly increased only in the PS group. Cardiac ultrasonography revealed atrioventricular valve regurgitation above grade 3 persisting in many patients from the PS group. Semilunar valve function after DKS operation did not progress to moderate or worse in any patients.'] |
['It has been established that microRNA expression and function contribute to phenotypic features of malignant cells, including resistance to apoptosis. Although targets and functional roles for a number of microRNAs have been described in cholangiocarcinoma, many additional microRNAs dysregulated in this tumor have not been assigned functional roles. In this study, we identify elevated miR-25 expression in malignant cholangiocarcinoma cell lines as well as patient samples. In cultured cells, treatment with the Smoothened inhibitor, cyclopamine, reduced miR-25 expression, suggesting Hedgehog signaling stimulates miR-25 production. Functionally, miR-25 was shown to protect cells against TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Correspondingly, antagonism of miR-25 in culture sensitized cells to apoptotic death. Computational analysis identified the TRAIL Death Receptor-4 (DR4) as a potential novel miR-25 target, and this prediction was confirmed by immunoblot, cell staining, and reporter assays.'] |
["Activating ATP-sensitive potassium (K(ATP)) channels improves ischemia tolerance of adult rabbit hearts. We hypothesize that (a) endogenous activation of the K(ATP) channel accounts for better ischemia tolerance of neonatal hearts and (b) exogenous K(ATP) channel activation with pinacidil further improves the neonatal heart's tolerance to cardioplegic ischemia.", "Study 1: Seven (control) neonatal rabbits received intraperitoneal saline, whereas five others (Glib) received 0.3 mg/kg glibenclamide 10 min before sacrifice. They were perfused on Langendorff with Krebs-Henseleit buffer (KHB). Baseline left ventricle (LV) performance and coronary flow (CF) were measured. After 20 min of 37 degrees C ischemia and 10 min of reperfusion, recovery was measured. Study 2: Ten (control) neonatal hearts underwent 90 min of normothermic ischemia with St. Thomas' cardioplegia (STCP) solution administered every 30 min. Ten others were pretreated with a 10-min infusion of 1 microM pinacidil in KHB and received 1 microM pinacidil-enriched STCP. Recovery of LV performance and CF were measured after 60 min of reperfusion.", 'Study 1: Glib significantly reduced preischemia LV performance by 28%* compared to control hearts. Recovery of Glib-treated hearts was significantly less (67%*) than controls (81%*). Study 2: Pinacidil-treated hearts had significantly better recovery of LV performance (39%*) and CF (78%*) compared to 23 and 52%, respectively, in untreated controls (*P < 0.05 vs control hearts).'] |
['Complex karyotype (CK) is the poorest risk factor in patients with myelodysplastic syndrome (MDS). It has recently been reported that monosomal karyotype (MK) worsens the prognosis of patients with CK. PATIENTS AND METHODS; We analyzed 1,054 adult patients with MDS with an abnormal karyotype from the Spanish Registry of MDS. The aim of the study was to describe the incidence, characteristics, and prognosis of MK; the main end points were overall survival (OS) and leukemia-free survival.', 'MK was identified in 172 patients (16%), most of whom (88%) presented with CK. Variables significantly associated with OS were age (hazard ratio [HR], 1.90; P < .001), bone marrow (BM) blast percentage (HR, 1.05; P < .001), hemoglobin level (HR, 1.71; P < .001), platelet count (HR, 1.41; P < .001), karyotype complexity (CK [three abnormalities]: HR, 1.81; P = .003; very CK [> three abnormalities]: HR, 2; P < .001), and abnormalities of chromosome 5 and/or 7 (HR, 1.89; P < .001). Variables significantly related to the risk of transformation to acute myeloid leukemia (AML) were higher BM blast percentage (HR, 1.12; P < .001) and karyotype complexity (CK: HR, 2.53; P = .002; very CK: HR, 2.77; P < .001).'] |
['Recent investigations have reported improved myocardial function during hypothermia following resuscitation from cardiac arrest. The effects of hypothermia on myocyte contractility were investigated under conditions of normal perfusion and after a 10min interval of ischemia.', 'Ventricular myocytes were obtained from 10 male Sprague-Dawley rats weighing 400+/-50g. The myocytes were randomized to be perfused at: 37 degrees C, 34 degrees C, 32 degrees C, or 30 degrees C. A subsequent set of myocytes was subjected to 10min of ischemia at 37 degrees C, prior to being randomized to reperfusion at: 37 degrees C, 34 degrees C, 32 degrees C or 30 degrees C. Myocyte contractility was expressed as length-shortening percentage. Intracellular Ca(2+) transients were assessed in a separate group of myocytes preloaded with Fura-2/AM. Sensitivity to Ca(2+) was tested by increasing perfusate Ca(2+) content, i.e. 0.5mM, 1mM and 2mM.', 'During normal perfusion and following reperfusion after 10min of ischemia, myocyte contractility increased at 34 degrees C compared to 37 degrees C (P<0.01). When the perfusion temperature was decreased to 32 degrees C and 30 degrees C, contractility further increased (P<0.001). Intracellular Ca(2+) transients were greater during perfusion at 34 degrees C compared to those at 37 degrees C (P<0.001) and further increased at 30 degrees C (P<0.001). Increases in extracellular Ca(2+) concentration from 0.5mM to 2mM resulted in greater myocyte contractility during perfusion at 30 degrees C compared to that observed at 37 degrees C (P<0.001). Effects of hypothermia on intracellular Ca(2+) transients and sensitivity to Ca(2+) persisted after ischemia.'] |
['To prospectively compare a novel type of valveless trocar that creates a curtain of pressurized carbon dioxide [CO(2)] gas (which maintains pneumoperitoneum at a lower gas flow rate) with standard trocars; to quantify the volume of CO(2) used; and to characterize CO(2) elimination during laparoscopic renal surgery.', 'A total of 51 patients undergoing laparoscopic renal surgery by a single surgeon were prospectively evaluated using either the valveless trocar (n = 26) or standard trocars (n = 25). Patient demographics, operative time, volume of CO(2) gas consumed, CO(2) elimination, perioperative parameters, and postoperative complications were recorded and analyzed.', 'Both patient cohorts were comparable in their preoperative demographics, including body mass index, the number of patients with chronic obstructive pulmonary disease, and smoking history. Mean operative time was lower in the valveless trocar cohort (124.1 minutes) compared with the conventional trocar group (145.6 minutes), P = .047. Use of the valveless trocar was associated with a lower volume of intraoperative CO(2) consumed (120.0 ± 82.8 vs 300.6 ± 191.5; P < .001) and reduced CO(2) elimination compared with standard trocar use after the first 16 minutes of insufflation (P < .05). Minimal complications occurred, including 2 cases of subcutaneous emphysema in the valveless trocar group, and 1 case of respiratory acidosis in the conventional trocar group.'] |
['Comatose patients resuscitated after out-of-hospital cardiac arrest receive therapeutic hypothermia. Bradycardia is frequent during therapeutic hypothermia, but its impact on outcome remains unclear. We explore a possible association between bradycardia during therapeutic hypothermia and neurologic outcome in comatose survivors of out-of-hospital cardiac arrest.', 'Retrospective cohort study, from January 2009 to January 2011.', 'University hospital medical and cardiac ICUs.', 'One hundred eleven consecutive comatose out-of-hospital cardiac arrest patients treated with therapeutic hypothermia.', 'Patients treated with standardized treatment protocol after cardiac arrest.', "All out-of-hospital cardiac arrest patients' records were reviewed. Hemodynamic data were obtained every fourth hour during the first days. The patients were in temperature target range (32-34°C) 8 hours after out-of-hospital cardiac arrest and dichotomized into bradycardia and nonbradycardia groups depending on their actual heart rate less than or equal to 60 beats/min or more than 60 beats/min at that time. Primary endpoint was Cerebral Performance Category score at hospital discharge. More nonbradycardia group patients received epinephrine during resuscitation and epinephrine and norepinephrine in the early in-hospital period. They also had lower base excess at admission. Survival rate with favorable outcome was significantly higher in the bradycardia than the nonbradycardia group (60% vs 37%, respectively, p = 0.03). For further heart rate quantification, patients were divided into quartiles: less than or equal to 49 beats/min, 50-63 beats/min, 64-77 beats/min, and more than or equal to 78 beats/min, with respective proportions of patients with good outcome at discharge of 18 of 27 (67%), 14 of 25 (56%), 12 of 28 (43%), and 7 of 27 (26%) (p = 0.002). Patients in the lowest quartile had significantly better outcome than the higher groups (p = 0.027), whereas patients in the highest quartile had significantly worse outcome than the lower three groups (p = 0.013)."] |
["Auditory discrimination is significantly impaired in Wernicke's aphasia (WA) and thought to be causatively related to the language comprehension impairment which characterises the condition. This study used mismatch negativity (MMN) to investigate the neural responses corresponding to successful and impaired auditory discrimination in WA.", 'Behavioural auditory discrimination thresholds of consonant-vowel-consonant (CVC) syllables and pure tones (PTs) were measured in WA (n\xa0=\xa07) and control (n\xa0=\xa07) participants. Threshold results were used to develop multiple deviant MMN\xa0oddball paradigms containing deviants which were either perceptibly or non-perceptibly different from the standard stimuli. MMN analysis investigated differences associated with group, condition and perceptibility as well as the relationship between MMN responses and comprehension (within which behavioural auditory discrimination profiles were examined).', 'MMN waveforms were observable to both perceptible and non-perceptible auditory changes. Perceptibility was only distinguished by MMN amplitude in the PT condition. The WA group could be distinguished from controls by an increase in MMN response latency to CVC stimuli change. Correlation analyses displayed a relationship between behavioural CVC discrimination and MMN amplitude in the control group, where greater amplitude corresponded to better discrimination. The WA group displayed the inverse effect; both discrimination accuracy and auditory comprehension scores were reduced with increased MMN amplitude. In the WA group, a further correlation was observed between the lateralisation of MMN response and CVC discrimination accuracy; the greater the bilateral involvement the better the discrimination accuracy.'] |
["The purpose of the present study was to determine the effect of feeding nutrient-enriched preterm formula to preterm infants until 6 months' corrected age (CA) on growth and development in the first 18 months of life.", "Very low-birthweight preterm infants were fed preterm formula until term (40 weeks CA). Infants were then assigned to one of three groups and were fed term formula until 6 months' CA (group 1, n= 29); preterm formula to 3 months' CA and then term formula to 6 months' CA (group 2, n= 30); or preterm formula until 6 months' CA (group 3, n= 31). Anthropometry was performed at term, 3, 6, 9, 12, 15, and at s18 months' CA. Mental and psychomotor development were assessed using the Bayley Scales of Infant Development II at 18 months' CA.", "Although body weight, length, head circumference and z score for CA at term in group 3 were significantly lower than those of groups 1 and 2, growth rates of these parameters were significantly higher in group 3 up to 18 months CA', as compared to groups 1 and 2. The mental developmental index and psychomotor developmental index of the Bayley test were not significantly different between the three groups."] |
['Delivery room cardiopulmonary resuscitation is rare. Recent evidence suggests that effective ventilation may be compromised during chest compressions (CC).', 'To determine whether trained neonatal personnel can assess effective ventilation during CC in the setting of changing lung compliance.', 'Neonatal providers (n=30) provided CC using a 3:1 CC to ventilation ratio performed for 2\u2005min, with lung compliance adjusted every 30\u2005s from 0.5 (low) to 1.0\u2005mL/cmH2O (normal), followed by face mask ventilation (FMV) alone for 1\u2005min. A neonatal lung simulator connected to a neonatal manikin was used to simulate the volume/pressure relation at low and normal compliance.', 'Group analysis showed no difference in peak inflating pressure (PIP) at low versus normal compliance, but a threefold increase in tidal volume (TV) (p=0.00005) during synchronised CC. Paired analysis demonstrated minimal change in PIP, but a significant decrease in TV at low versus normal compliance. During FMV only, a significant decrease in PIP and increase in TV was noted with improved compliance. The face mask was incorrectly applied in 12 (40%) cases and in 20/30 (67%) providers did not perceive a change in compliance. During FMV only, 7/30 (23%) took corrective steps to achieve chest rise.'] |
['Limited research suggests that alcohol consumed with an artificially sweetened mixer (e.g., diet soft drink) results in higher breath alcohol concentrations (BrACs) compared with the same amount of alcohol consumed with a similar beverage containing sugar. The purpose of this study was to determine the reliability of this effect in both male and female social drinkers and to determine if there are measureable objective and subjective differences when alcohol is consumed with an artificially sweetened versus sugar-sweetened mixer.', 'Participants (n\xa0=\xa016) of equal gender attended 3 sessions where they received 1 of 3 doses (1.97\xa0ml/kg vodka mixed with 3.94\xa0ml/kg Squirt, 1.97\xa0ml/kg vodka mixed with 3.94\xa0ml/kg diet Squirt, and a placebo beverage) in random order. BrACs were recorded, as were self-reported ratings of subjective intoxication, fatigue, impairment, and willingness to drive. Objective performance was assessed using a cued go/no-go reaction time task.', 'BrACs were significantly higher in the alcohol\xa0+\xa0diet beverage condition compared with the alcohol\xa0+\xa0regular beverage condition. The mean peak BrAC was 0.091\xa0g/210\xa0l in the alcohol\xa0+\xa0diet condition compared with 0.077\xa0g/210\xa0l in the alcohol\xa0+\xa0regular condition. Cued go/no-go task performance indicated the greatest impairment for the alcohol\xa0+\xa0diet beverage condition. Subjective measures indicated that participants appeared unaware of any differences in the 2 alcohol conditions, given that no significant differences in subjective ratings were observed for the 2 alcohol conditions. No gender differences were observed for BrACs, and objective and subjective measures.'] |
['Early markers of axonal and clinical outcomes are required for early phase testing of putative neuroprotective therapies for multiple sclerosis (MS).', 'To assess whether early measurement of diffusion tensor imaging (DTI) parameters (axial and radial diffusivity) within the optic nerve during and after acute demyelinating optic neuritis (ON) could predict axonal (retinal nerve fibre layer thinning and multi-focal visual evoked potential amplitude reduction) or clinical (visual acuity and visual field loss) outcomes at 6 or 12 months.', 'Thirty-seven patients presenting with acute, unilateral ON were studied at baseline, one, three, six and 12 months using optic nerve DTI, clinical and paraclinical markers of axonal injury and clinical visual dysfunction.', 'Affected nerve axial diffusivity (AD) was reduced at baseline, 1 and 3 months. Reduced 1-month AD correlated with retinal nerve fibre layer (RNFL) thinning at 6 (R=0.38, p=0.04) and 12 months (R=0.437, p=0.008) and VEP amplitude loss at 6 (R=0.414, p=0.019) and 12 months (R=0.484, p=0.003). AD reduction at three months correlated with high contrast visual acuity at 6 (ρ = -0.519, p = 0.001) and 12 months (ρ = -0.414, p=0.011). The time-course for AD reduction for each patient was modelled using a quadratic regression. AD normalised after a median of 18 weeks and longer normalisation times were associated with more pronounced RNFL thinning and mfVEP amplitude loss at 12 months. Affected nerve radial diffusivity (RD) was unchanged until three months, after which time it remained elevated.'] |
['Studies have shown that serum total immunoglobulin E (IgE) levels are higher in asthmatics. However, the role of the serum total IgE level, independently from atopy, in adult asthma is not understood. We studied the associations between serum total IgE, the number of sensitizations and the sum of specific IgEs and new-onset asthma using longitudinal data from the European Community Respiratory Health Survey.', 'Serum total and specific IgE to 4 common inhalant allergens were measured at baseline in 9,175 participants, with a follow-up of 9 years. Individuals with asthma history and/or asthma symptoms were excluded. Atopy was defined as the presence of at least one specific IgE ≥0.35 kU/l. Total and specific IgEs were regressed against new-onset asthma using multivariate logistic regression with a random intercept for the study centre.', 'Two hundred and ninety-seven participants had developed asthma during follow-up (incidence rate 5.7 per 1,000 person-years). A 10% higher level of total IgE was associated with a 12% increased risk of new-onset asthma (p = 0.005). However, after adjustment for the number of positive specific IgEs [odds ratio (OR) for multiple sensitization 1.74, 95% confidence interval (CI) 1.05–2.88] and the sum of allergenspecific IgEs (OR 1.18, 95% CI 1.00–1.40), the association between total IgE and asthma disappeared (OR 1.00, 95% CI 0.91–1.10). Seventeen percent of new-onset asthma cases could be attributed to atopy, and this estimate was not largely modified when the total IgE level was simultaneously taken into account.'] |
['The purpose of this study was to retrospectively analyze results obtained in 22 patients affected by malignant high-grade chest wall tumors evaluated preoperatively by ultrasonography as well as other imaging techniques.', 'Twenty-two patients with chest wall high-grade sarcomas routinely underwent computed tomography, magnetic resonance imaging, total body scintigraphy, and ultrasonography. Ultrasonography was always performed by the same person using an ultrasonography system with a 5- to 13-MHz probe and with color Doppler evaluation of the lesion. Scans were done with the patient positioned as during surgery. Tumor lateral margins were identified, and a line was marked at 4 cm. In 8 patients with local recurrence, the presence of micronodules was also studied. Results of computed tomography, magnetic resonance imaging, and ultrasonography were compared with the surgical specimens.', 'Histologically, all surgical specimens excised according to ultrasonographic margins showed wide margins. Ultrasonography showed micronodules in 6 of 8 patients with local recurrence; histologically, they were all identified as sarcoma nodules. Ultrasonography failed in particular with cervical-mediastinal vessels.'] |
['The role of cortisol in the prediction of mortality risk in critical illness is controversial in the literature. The aim of this study was to evaluate the prognostic value of cortisol concentrations in a mixed population of critically ill patients in medical emergencies.', 'In this prospective, observational study, measurement of total (TC) and free cortisol (FC) levels was made in the serum samples of 69 critically ill patients (39 males and 30 females, median age of 74 years) at admission (0\u200ah) and 6, 24, 48, and 96\u200ah after admission.', 'Cortisol levels were determined using HPLC coupled high-resolution ESI-TOF mass spectrometry. The severity of disease was calculated by prognostic scores. Statistical analyses were performed using the SPSS 22.0 software.', 'The range of TC varied between 49.9 and 8797.8 nmol/l, FC between 0.4 and 759.9\u200anmol/l. The levels of FC at 0, 6, 24, and 48\u200ah and TC at 0, 6\u200ah were significantly elevated in non-survivors and correlated with the predicted mortality. The prognostic value of these cortisol levels was comparable with the routinely used mortality scores. In predictive models, FC at 6, 24, and 48\u200ah proved to be an independent determinant of mortality.'] |
['It is not yet known whether preoperative combined radiotherapy and chemotherapy for rectal cancer affects postoperative mortality and morbidity. We therefore evaluated early postoperative complications in patients given adjuvant radiotherapy and chemotherapy before surgery for middle and lower rectal adenocarcinoma.', 'Between 1994 and 1998, 41 patients underwent combined preoperative pelvic radiotherapy and chemotherapy at our institution. Most of the patients had 45 Gy (1.8 Gy/day/25 fractions) during five weeks plus 5-fluorouracil (350 mg/m2/day) and low-dose leucovorin (10 mg/m2/day) bolus on Days 1 to 5 and 29 to 33. Surgery was performed four to six weeks after completion of adjuvant therapy. The 41 patients (Group A) were retrospectively compared with 30 patients (Group B) who, in the same period, underwent surgery without preoperative adjuvant therapy. The groups were homogeneous for age, gender, preoperative risk factors, operating surgeon, and pathologic stage. Mean distance of the tumor from the anal verge was shorter in Group A patients (P = 0.031).', 'There were seven major postoperative complications in each group. No significant differences were found between the groups for morbidity and mortality rates. Considering all patients, more postoperative complications were found in patients scored as American Society of Anesthesiologists 3, in those with a preoperative hemoglobin value < 10 g/dl, and in those without a diverting stoma (P = 0.0048, P = 0.0453, and P = 0.0033, respectively). At multivariate analysis, independent predictors of major complications were American Society of Anesthesiologists score (relative risk, 343; P = 0.022), diverting stoma (relative risk, 159; P = 0.010), type of surgical procedure (relative risk, 38.9; P = 0.048), preoperative hemoglobin value (relative risk, 9.72; P = 0.061), and intraoperative blood loss (relative risk, 1; P = 0.027). In Group A patients, the absence of diverting stomas was associated with major postoperative complications (P = 0.0307), and independent predictors of major complications were American Society of Anesthesiologists score (relative risk, 56; P = 0.111) and absence of a diverting stoma (relative risk, 22.42; P = 0.222).'] |
['Worsening renal function (WRF) during the treatment of decompensated heart failure, frequently defined as an absolute increase in serum creatinine >or=0.3 mg/dl, has been reported as a strong adverse prognostic factor in several studies. We hypothesized that this definition of WRF is biased by baseline renal function secondary to the exponential relationship between creatinine and renal function.', 'We reviewed consecutive admissions with a discharge diagnosis of heart failure. An increase in creatinine >or=0.3 mg/dl (WRF(CREAT)) was compared to a decrease in GFR >or=20% (WRF(GFR)).', 'Overall, 993 admissions met eligibility. WRF(CREAT) occurred in 31.5% and WRF(GFR) in 32.7%. WRF(CREAT) and WRF(GFR) had opposing relationships with baseline renal function (OR = 1.9 vs. OR = 0.51, respectively, p < 0.001). Both definitions had similar unadjusted associations with death at 30 days [WRF(GFR) OR = 2.3 (95% CI 1.1-4.8), p = 0.026; WRF(CREAT) OR = 2.1 (95% CI 1.0-4.4), p = 0.047]. Controlling for baseline renal insufficiency, WRF(GFR) added incrementally in the prediction of mortality (p = 0.009); however, WRF(CREAT) did not (p = 0.11).'] |
['Upstream transcription factor 1 (USF1) regulates genes of glucose and lipid metabolism. Polymorphisms in the USF1 gene showed association with familial combined hyperlipidemia and lipid parameters. The aim of our study was to examine the associations between USF1 polymorphisms and lipid parameters as well as incident type 2 diabetes mellitus (T2DM) in German Caucasians.', 'We genotyped eight polymorphisms in the USF1 gene in 2067 middle-aged (35-74 years) individuals including 498 incident T2DM cases and 1569 non-cases of the population-based case-cohort study from the MONICA/KORA Augsburg project.', 'Six polymorphisms and their haplotypes were analyzed using multivariable linear regression and Cox proportional hazards models.', 'Polymorphism rs3737787 was inversely associated with incident T2DM in women with decreased risk for female heterozygotes compared with women homozygous for the major allele (Hazard ratio=0.57; 95% confidence intervals: 0.38-0.87; P=0.008). After correction for multiple testing, significance remained. Polymorphisms rs3813609 and rs1556259 were significantly associated with reduction in low-density lipoprotein (LDL) cholesterol (p(NOM)=0.001; p(NOM)=0.00002) in women. Analyses also indicated associations of haplotypes with LDL cholesterol in women, but the association lost statistical significance after correction for multiple testing. Total serum cholesterol (TC) and high-density lipoprotein (HDL) cholesterol were weakly associated (P<0.05) with USF1 polymorphisms in women. No significant associations were found in men.'] |
['To determine the effect of keratinocyte growth factor (KGF), a mesenchymally derived epithelial growth factor that can cause proliferation of pulmonary, gastrointestinal and mammary epithelia, on urothelium.', 'Recombinant human KGF was systemically administered to rats and Rhesus monkeys, and the proliferative effects on the bladder were evaluated.', 'Keratinocyte growth factor causes proliferation of transitional epithelial cells. Proliferating cell nuclear antigen (PCNA) expression in rat bladder is dramatically increased along the basal layer of urothelium 1, 3, 7 and 14 days after daily injections of KGF. Incorporation of 5-bromodeoxyuridine (BrdU) at 7 and 14 days in the urothelium of KGF-treated rats parallels PCNA immunoreactivity and confirms that KGF increases DNA synthesis in urothelial cells. Urothelial cell proliferation is accompanied histologically by an increase in mitotic activity. Keratinocyte growth factor-induced PCNA expression is reversible upon cessation of KGF administration. Keratinocyte growth factor mRNA and receptor mRNA are detected by whole organ RNAase protection assays of the urinary bladder and the kidney of normal rats. Rhesus monkeys receiving KGF for 7 days demonstrate a dramatic incorporation of BrdU in the urothelium of the bladder and renal pelvis as well as in the collecting ducts of the kidney.'] |
['Myocardial injury following ischaemia and reperfusion has been attributed to activation and transmigration of polymorphonuclear leukocytes (PMNs) with release of mediators including oxygen-derived radicals and proteases causing damage.', 'We studied the serine protease inhibitor aprotinin in an in vivo rabbit model of 1 h of myocardial ischaemia followed by 3 h of reperfusion (MI+R). Aprotinin (10,000 Ukg(-1)) or its vehicle were injected 5 min prior to the start of reperfusion.', 'Myocardial injury was significantly reduced with aprotinin treatment as indicated by a reduced necrotic area (11+/-2.7% necrosis as percentage of area at risk after aprotinin; 24+/-3.1% after vehicle; P<0.05) and plasma creatine kinase activity (12.2+/-1.5 and 17.3+/-2.3 IU g(-1) protein in aprotinin and vehicle groups, respectively, P<0.05). PMN infiltration (assessed by myeloperoxidase activity) was significantly decreased in aprotinin-treated animals compared to vehicle (P<0.01). Histological analysis also revealed a substantial increase in PMN infiltration following MI+R and this was significantly reduced by aprotinin therapy (44+/-15 vs 102+/-2 PMN mm2 in aprotinin vs vehicle-treated animals, P<0.05). In parallel in vitro experiments, aprotinin inhibited neutrophil-endothelium interaction by reducing PMN adhesion on isolated, activated aortic endothelium. Finally, immunohistochemical analysis illustrated aprotinin significantly reduced myocardial apoptosis following MI+R.'] |
['The therapeutic potential of adipose-derived stem cells (ASCs) is reduced by various stress-inducing conditions that affect tissue homeostasis such as diabetes, aging, and obesity. Previous works have provided evidence of negative effects of obesity on ASC populations, but it is unclear whether this persists after a weight loss. This study evaluated whether weight loss can restore the attenuated properties found in ASCs derived from populations with obesity (oASCs).', 'In vitro functional analyses were performed to investigate the possible recovery properties in mouse oASCs. Using ASCs isolated from subcutaneous tissue from formerly obese mice (dASCs) and control mice (cASCs), cell proliferation, viability, and some regenerative properties in these cells were analyzed compared with oASCs to evaluate the functional cell state.', 'Cell proliferation, viability, and some regenerative properties are strengthened in dASCs and cASCs compared with oASCs. Nevertheless, metabolic analysis reveals a mitochondrial load misbalance and function leading to impaired respiration in dASCs.'] |
['Epilepsy is a serious brain disorder characterized by recurrent unprovoked seizures. Approximately two-thirds of seizures can be controlled with antiepileptic medications (Kwan 2000). For some of the others, surgery can completely eliminate or significantly reduce the occurrence of disabling seizures. Localization of epileptogenic areas for resective surgery is far from perfect, and new tools are being investigated to more accurately localize the epileptogenic zone (the zone of the brain where the seizures begin) and improve the likelihood of freedom from postsurgical seizures. Recordings of pathological high-frequency oscillations (HFOs) may be one such tool.', 'To assess the ability of HFOs to improve the outcomes of epilepsy surgery by helping to identify more accurately the epileptogenic areas of the brain.', 'We searched the Cochrane Epilepsy Group Specialized Register (15 April 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 3), MEDLINE (Ovid) (1946 to 15 April 2013), CINAHL (EBSCOhost) (15 April 2013), Web of Knowledge (Thomson Reuters) (15 April 2013), www.clinicaltrials.gov (15 April 2013), and the World Health Organization International Clinical Trials Registry Platform (15 April 2013).', 'We included studies that provided information on the outcomes of epilepsy surgery at at least six months and which used high-frequency oscillations in making decisions about epilepsy surgery.', 'The primary outcome of the review was the Engel Class Outcome System. Secondary outcomes were responder rate, International League Against Epilepsy (ILAE) epilepsy surgery outcome, frequency of adverse events from any source and quality of life outcomes. We intended to analyse outcomes via an aggregated data fixed-effect model meta-analysis.', 'Two studies met the inclusion criteria. Both studies were small non-randomised trials, with no control group and no blinding. The quality of evidence for all outcomes was very low. The combination of these two studies resulted in 11 participants who prospectively used ictal HFOs for epilepsy surgery decision making. Results of the postsurgical seizure freedom Engel class I to IV outcome were determined over a period of 12 to 38 months (average 23.4 months) and indicated that six participants had an Engel class I outcome (seizure freedom), two had class II (rare disabling seizures), three had class III (worthwhile improvement). No adverse effects were reported. Neither study compared surgical results guided by HFOs versus surgical results guided without HFOs.'] |
["Obesity and type 2 diabetes mellitus are characterized by insulin resistance and 'low-grade inflammation'; however, the pathophysiological link is poorly understood. To determine the relative contribution of obesity and insulin resistance to systemic 'inflammation', this study comprehensively characterized circulating immune cells in different grades of obesity.", 'Immune cell phenotypes and activation status were analysed by flow cytometry cross-sectionally in morbidly obese (n = 16, body mass index (BMI) 42.2 ± 5.4 kg/m2), overweight (n = 13, BMI 27.4 ± 1.6 kg/m2) and normal weight (n = 12, BMI 22.5 ± 1.9 kg/m2) subjects.', 'Obese, but not overweight subjects, had increased activation marker expression on neutrophils, monocytes, T-lymphocytes and polarization of T helper cells towards a pro-inflammatory type 1-phenotype (Th1). Th1 numbers correlated positively with the degree of insulin resistance (homeostasis model assessment, p < 0.05). Lymphocytes from obese subjects showed reduced insulin-stimulated AKT-phosphorylation in vitro. Supra-physiological insulin concentrations did not affect T-cell differentiation, which under normal circumstances would promote an anti-inflammatory T helper type 2-phenotype.'] |
['The purpose of this study was to investigate the genetic background for the previously reported finding of an increased frequency of low levels of mannan-binding lectin in couples with unexplained recurrent spontaneous abortion and to evaluate the impact of low mannan-binding lectin levels on future pregnancy outcome.', "Mannan-binding lectin levels were measured in 217 women with unexplained recurrent spontaneous abortion and 111 of their husbands and were compared with corresponding measurements in 104 couples with uncomplicated reproductive histories and 210 blood donors. An investigation of the genetic polymorphism, which is largely responsible for serum mannan- binding lectin levels, was done by polymerase chain reaction methods with DNA from a subset of the patients and control subjects. Information was collected about the outcome of the patients' next pregnancies, together with perinatal data concerning the patients' first birth that occurred before or after being assigned to the study.", 'Among women with recurrent spontaneous abortion, 18.9% of the women had mannan-binding lectin levels of </= 100 ng/mL compared with 12.2% of control subjects ( P =.02). An investigation of mannan-binding lectin levels and genetic analyses gave no evidence that paternal mannan- binding lectin deficiency plays a role for recurrent spontaneous abortion. Patients with mannan-binding lectin levels of </=100 ng/mL had a higher abortion rate than patients with normal mannan- binding lectin levels (P <.05). The median birth weight of children who were born at term of women with recurrent spontaneous abortion was 287 g less in women with mannan-binding lectin levels of </= 100 ng/mL than that of patients with normal mannan-binding lectin levels (P =.04).'] |
['The role of alpha2-antiplasmin (alpha2-AP) on platelet aggregation was investigated using mice deficient in alpha2-AP (alpha2-AP(-/-)) or using wild type mice (alpha2-AP(+/+)).', 'Blood samples were taken from each mouse under anesthesia with ether and platelet rich plasma (PRP) was prepared. Platelet aggregation induced by various doses of ADP (0.3-30 microM) was detected using a laser-light scattering (LS) system. Aggregated forms were observed using a scanning electron microscopy (SEM).', 'Dose-dependent platelet aggregation was not different in both types of mice. However, platelet micro-aggregate formation in alpha2-AP(-/-) mice induced by low dose of ADP (1.0 microM) markedly increased compared to the situation in wild type mice. Aggregated form detected by SEM showed supported data from LS analysis. When washed platelets of alpha2-AP(+/+) mice were resuspended in plasma of alpha2-AP(-/-) mice, platelet micro-aggregation was also increased. On the contrary, when washed platelets of alpha2-AP(-/-) mice were suspended in plasma of alpha2-AP(+/+) mice, platelet micro-aggregation did not change. In separate experiments, tPA (1.0 microg/ml) was added to PRP before the stimulation of ADP. tPA had no effect on platelet aggregation in alpha2-AP(+/+) mice, however platelet micro-aggregation in alpha2-AP(-/-) mice was markedly increased by the treatment with tPA. Moreover, the amount of released ATP from stimulated platelets was increased in alpha2-AP(-/-) mice treated with tPA.'] |
['Chronic airway inflammation is a fundamental feature of bronchial asthma, which is characterized by the accumulation and activation of inflammatory cells, such as mast cells and eosinophils, that are tightly regulated by TH2 cytokines and chemokines. Recently, we demonstrated, in a murine model of asthma with immunosuppressed mice reconstituted with antigen-specific IgE or IgG1 antibodies, that IgE, but not IgG1, participates in potentiation of airway inflammation and induction of airway hyperreactivity (AHR). The IgG1 antibody, however, did not elicit passive cutaneous anaphylactic reactions, which was in contrast to IgE.', 'Because 2 types of murine IgG1 have been demonstrated with regard to anaphylactic activity, the present experiments were undertaken to determine the role of anaphylactic and nonanaphylactic IgG1 antibodies in the development of antigen-induced eosinophilia and AHR in this model.', "Dinitrophenyl-conjugated, heat-coagulated hen's egg white was implanted in immunosuppressed mice reconstituted with anaphylactic or nonanaphylactic IgG1. Intratracheal challenge with aggregated dinitrophenyl-ovalbumin was performed on day 14, and lung inflammatory and mechanical parameters were evaluated after 48 hours.", 'Our results demonstrated that reconstitution of immunosuppressed mice with anaphylactic IgG1 antibodies in contrast to nonanaphylactic IgG1 antibodies potentiates their ability to have pulmonary eosinophilic inflammation and AHR. IL-5 and eotaxin levels in bronchoalveolar lavage fluid from anaphylactic IgG1-reconstituted mice were also higher than those in nonanaphylactic IgG1-reconstituted mice.'] |
['Sporadic fundic gland polyps (FGPs) are common gastric polyps. Some studies reported that FGPs dramatically increased due to proton pump inhibitors (PPIs) use and a decreased prevalence of Helicobacter pylori (H. pylori) infection in Western countries. However, data are still controversial. This study aimed to identify the relationships between these two factors and FGPs in China.', "Consecutive patients with FGPs detected were retrospectively analyzed. Data including patients' age, sex, symptoms, H. pylori infection, history of PPIs use, and the polyps were documented. Each patient was compared with two randomly selected age- and sex-matched controls with similar symptoms in the same period.", 'During the period from March 2011 to March 2012, a total of 328 patients were diagnosed as FGPs in 23 047 patients who underwent routine esophagogastroduodenoscopy and 656 patients without FGPs as controls. The mean age was (55.12±12.61) years, and 75.91% were women. The prevalence of H. pylori in patients with FGPs was significantly lower than in those without FGPs (22.30% (64/287) vs. 42.26% (224/530), P < 0.001, OR 0.392, 95% CI 0.283-0.544). Overall, a total of 54 patients with FGPs (54/328, 16.46%) and 136 patients without FGPs (136/656, 20.73%) received PPIs therapy (P = 0.110). According to the different duration of PPIs use, no significant differences of PPIs use were found between the cases and controls among all subgroups. Moreover, the PPIs use was also similar, regardless of age, sex, H. pylori infection, and the number of polyps.'] |
['The effect of anaesthesia induced by intrathecal injection of 6.3% MgSO4 or 4% lidocaine on intracellular electrolyte homeostasis in spinal cord neurones of a rat model was investigated.', 'Intracellular Ca2+, Mg2+, Na+ and K+ concentrations were determined at different times after intrathecal administration of NaCl (saline, a control group), MgSO4 or lidocaine.', "In both thoracic and lumbar spinal cord segments, Ca2+ concentrations rose significantly 30 min and 2 h after 6.3% MgSO4 injection, and after 24 h were still significantly increased compared with the values obtained from the control group which were subjected to sham 'anaesthesia' by saline injection (172, 121 and 108 ng mg-1 protein vs. control 23 ng mg-1 protein, respectively, in the thoracic segment and 222, 229 and 176 ng mg-1 protein vs. control 43 ng mg-1 protein, respectively, in the lumbar segment). Lidocaine injection also produced a significant increase in intracellular Ca2+ in the thoracic and lumbar spinal cord segments (69, 64 and 53 ng mg-1 protein vs. control 33.4 ng mg-1 protein and 26, 94 and 46 ng mg-1 protein vs. 23 ng mg-1 protein respectively). Only a modest rise in intracellular Mg2+ was observed after intrathecal MgSO4 or lidocaine injection (27 ng mg-1 protein vs. 23 ng mg-1 protein). Na+ and K+ concentrations decreased 24 h after MgSO4 and 1 h after lidocaine injection."] |
['Insulin has direct effects on blood flow in various tissues, most likely due to endothelial NO production. We investigated whether insulin delivered to the skin by iontophoresis increases microvascular perfusion and whether this effect is partly or completely mediated by the release of NO.', 'In healthy subjects, regular insulin and monomeric insulin were delivered to the skin by cathodal iontophoresis. The skin was pretreated either with L-NAME or control solution (PBS) using anodal iontophoresis. Microvascular responses were measured using laser Doppler flowmetry.', 'A dose-dependent increase in perfusion was observed during iontophoresis of regular and monomeric insulin. The maximum perfusion was significantly elevated compared with control after PBS (regular insulin 53.6 (12.7-95.6) PU vs. 4.2 (3.4-4.8) PU, p = 0.002; monomeric insulin 32.6 (8.9-92.6) PU vs. 5.9 (3.4-56.0) PU, p = 0.03). The microvascular response to insulin was abolished after L-NAME (regular insulin: 25.6 (11.6-54.4) PU vs. control: 4.7 (2.9-11.5) PU, p = 0.15; monomeric insulin 10.9 (5.4-56.8) PU vs. control: 4.7 (2.9-11.5) PU, p = 0.22).'] |
['Although the signalling pathways of late preconditioning have been extensively investigated, its consequence for myocardial metabolism remains unknown. Thus, myocardial oxygen consumption (MVO2) was evaluated before and under late preconditioning.', 'In 7 chronically instrumented dogs, we measured MVO2 in vivo at baseline and during inotropic stimulation with dobutamine (10 and 20 microg/kg/min, i.v.) before (Day 0) and 24 h after (Day 1) a 10-min circumflex coronary artery occlusion.', 'At Day 0, dobutamine dose-dependently increased the triple product (heart ratexleft ventricular systolic pressurexleft ventricular maximum dP/dt), MVO2, coronary blood flow, and coronary sinus pO2. At Day 1, the triple product was similar at baseline and at each dose of dobutamine but MVO2 was significantly blunted as compared to Day 0 (-15+/-4%, -22+/-3% and -19+/-4% at baseline, dobutamine 10 and 20 microg/kg/min, respectively). Importantly, the relationship between MVO2 and triple product was significantly rightward shifted with late preconditioning, i.e., MVO2 was reduced for any level of triple product. At Day 1, the relationship between coronary blood flow and MVO2 was not altered as compared to Day 0 but coronary sinus pO2 was significantly increased vs. Day 0 for any level of coronary blood flow, suggesting that late preconditioning exerted no vasomotor effect but rather changed myocardial oxygen handling. These effects were abolished by administration of S-methyl-isothiourea (1.5 mg/kg, i.v.), a iNOS inhibitor.'] |
['The number of available donor lungs is still the limiting factor in lung transplantation. We have recently shown that diluted surfactant lavage during ex vivo lung evaluation improved the graft function after gastric acid aspiration. In the present study, we hypothesized that diluted surfactant administration would recondition and improve the graft function after acid aspiration-induced lung injury in a porcine model of pulmonary transplantation.', 'Left lung injury was induced by intrabronchial administration of 1 mL/kg betaine HCl and pepsin mixture. The animals were subsequently ventilated for 24 hours. After organ retrieval, the donor lungs were stored at 4°C for 4 hours. In the control group, left lung transplantation was performed without any surfactant treatment. In the surfactant group, the recipients received intratracheal diluted surfactant lavage just before reperfusion and ventilation. During 7 hours of reperfusion, the hemodynamic and respiratory variables were recorded on an hourly basis.', 'Surfactant lavage resulted in lower mean pulmonary artery pressure, higher mixed venous oxygen saturation, and better oxygenation compared with the control group (p = 0.001). Bronchoalveolar lavage interleukin-6 level, protein, and neutrophil percentage at the end of the experiment were significantly higher in the control group compared with the surfactant group (p = 0.03). Minimal surface tension was significantly lower in the surfactant group compared with controls (p = 0.03).'] |
['Benign prostatic hyperplasia is an age- and androgen-dependent condition of urethral compression caused by prostatic contractility and glandular enlargement. In this study we investigate whether testosterone, dihydrotestosterone and estradiol modulate the ability of human cultured prostatic stromal cells (HCPSCs) to respond to the adrenoceptor agonists, noradrenaline (30 microM) and phenylephrine (100 microM), the protein kinase C activating phorbol ester, phorbol diacetate (PDA, 10 microM), and the L-type Ca(2+) channel activator, (-)-Bay K8644 (Bay K, 10 microM) with elevations of intracellular Ca(2+) ([Ca(2+)](i)).', 'Cells were loaded with the Ca(2+) sensitive fluorophore, FURA-2AM (10 microM) and changes in intracellular Ca(2+) determined before and 8-12 min after ligand addition.', 'Compared to steroid-free (SF) controls, the incubation of HCPSC with testosterone (30 and 300 pM) significantly increased responses to both noradrenaline and phenylephrine. Responses to Bay K were significantly reduced between 30 nM to 300 pM but responses to PDA were not greatly affected. Compared to SF the addition of estradiol (E(2), 100 pM) did not affect responses to phenylephrine. The concomitant addition of dihydrotestosterone (DHT) and E(2) (to give ratios from 1:1 to 1,000:1) elevated the responses to noradrenaline and phenylephrine at the extreme ranges. Responses to PDA and Bay K generally increased as DHT:E(2) approached unity.'] |
['White-matter microstructure, known to undergo significant developmental transformation, is abnormal in bipolar disorder (BD). Available evidence suggests that white-matter deviation may be more pronounced in pediatric than adult-onset BD. The present study aimed to examine how white-matter microstructure deviates from a typical maturational trajectory in BD.', 'Fractional anisotropy (FA) was measured in 35 individuals presenting with first episode BD (type I) and 46 healthy controls (HC) (aged 9-42) using diffusion tensor imaging (DTI). Patients were medication free and close to illness onset at the time of the DTI scans. Tract-based spatial statistics were used to examine the center of white-matter tracts, and FA was extracted from nine tracts of interest. Axial, radial, and mean diffusivity were examined in post-hoc analyses.', 'The left anterior limb of the internal capsule (ALIC) showed significantly lower FA in pediatric than adult-onset BD. The lower FA in BD was due primarily to greater radial, rather than decreased axial, diffusivity.'] |
['Our aim was to investigate whether and at what stage hypermethylation of the tachykinin-1 (TAC1) gene is associated with human esophageal neoplastic transformation.', 'TAC1 promoter hypermethylation was examined by real-time methylation-specific PCR in 258 human esophageal specimens and 126 plasma samples from patients or tissues at various stages of neoplastic evolution.', "TAC1 hypermethylation in tissue samples showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) from normal esophagus (P < 0.0001). Both frequencies and normalized methylation values of TAC1 tissue methylation were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's esophagus, EAC, and ESCC than in normal esophagus (P < 0.01). The frequency of TAC1 hypermethylation increased dramatically and early during neoplastic progression, from 7.5% in normal esophagus to 55.6% in BE from patients with Barrett's metaplasia alone, 57.5% in dysplastic Barrett's esophagus, and 61.2% in EAC. There was a significant relationship between TAC1 hypermethylation and BE segment length, a known clinical risk factor for neoplastic progression. Twelve (50%) of 24 ESCC exhibited TAC1 hypermethylation. Overall patient survival correlated significantly with TAC1 methylation status in ESCC patients (mean survival, 22 versus 110 months; P = 0.0102, log-rank test), but not in EAC patients. Both mean normalized methylation values and frequency of TAC1 hypermethylation in plasma samples were significantly higher in EAC patients than in control subjects. Treatment of KYSE220 ESCC and BIC EAC cells with 5-aza-2'-deoxycytidine reduced TAC1 methylation and increased TAC1 mRNA expression."] |
['Obesity is associated with an overexpansion of adipose tissue, along with increases in blood pressure, glycemia, inflammation, and thrombosis. Research to develop nutritional interventions to prevent or treat obesity and its associated diseases is greatly needed. Previously, we demonstrated the ability of eicosapentaenoic acid (EPA) to prevent high-fat (HF) diet-induced obesity, insulin resistance, and inflammation in mice.', 'The objective of the current study was to determine the mechanisms mediating the anti-inflammatory and antilipogenic actions of EPA.', 'In a previous study, male C57BL/6J mice were fed a low-fat diet (10% of energy from fat), an HF diet (45% of energy from fat), or an HF diet supplemented with EPA (45% of energy from fat; 36 g/kg EPA; HF+EPA) for 11 wk or an HF diet for 6 wk and then switched to the HF+EPA diet for 5 wk. In this study, we used histology/immunohistochemistry, gene expression, and metabolomic analyses of white adipose tissue from these mice. In addition, cultured mouse 3T3-L1 adipocytes were treated with 100 μM EPA for 48 h and then used for extracellular flux assays with untreated 3T3-L1 adipocytes used as a control.', 'Compared with the HF diet, the HF+EPA diet significantly reduced body weight, adiposity, adipocyte size, and macrophage infiltration into adipose tissue. No significant differences in overall body weight or fat pad weights were observed between HF-fed mice vs. those fed the HF+EPA diet for a short time after first inducing obesity with the HF diet. Interestingly, both histology and immunohistochemistry results showed a significantly lower mean adipocyte size and macrophage infiltration in mice fed the HF diet and then switched to the HF+EPA diet vs. those fed HF diets only. This indicated that EPA was able to prevent as well as reverse HF-diet-induced adipocyte inflammation and hypertrophy and that some of the metabolic effects of EPA were independent of body weight or adiposity. In addition, adipose tissue metabolomic data and cultured adipocyte extracellular flux bioenergetic assays indicated that EPA also regulated mitochondrial function by increasing fatty acid oxidation and oxygen consumption, respectively.'] |
['Tumor necrosis factor-alpha (TNFalpha) is a pleiotropic cytokine exerting both inflammatory and cell death modulatory activity, and is thought to play a role in the pathogenesis of atherosclerosis. Studies in mice indicated that TNFalpha affects atherosclerosis minimally or not under conditions that allow fatty streak formation. Here, we examined the possible role of TNFalpha in advanced and complex atherosclerotic lesions.', 'To induce atherosclerosis, TNFalpha-deficient (Tnf-/-) APOE*3-Leiden and control APOE*3-Leiden only mice were fed a cholesterol-rich diet. Comparable levels of plasma cholesterol and triglycerides and the systemic inflammatory parameters, serum amyloid A and soluble intercellular adhesion molecule-1 were found in APOE*3-LeidenTnf-/- and control mice. Although absence of TNFalpha did not affect the quantitative area of atherosclerosis, APOE*3-LeidenTnf-/- mice had a higher relative number of early lesions (46.1% vs. 21.4%) and a lower relative number of advanced lesions (53.9% vs. 78.6%, P=0.04). In addition, the advanced lesions in APOE*3-LeidenTnf-/- mice showed less necrosis (9.9+/-12.1% vs. 23.4+/-19.3% of total lesion area, P=0.04) and an increase in apoptosis (1.5+/-1.5% vs. 0.4+/-0.6% of total nuclei, P=0.03).'] |
['Recurrent ischemic events occur during the hospital stay of 7-32% of patients after successful thrombolytic treatment of acute myocardial infarction (AMI).', 'To define the association between postinfarction angina pectoris and the clinical, angiographic, and intravascular ultrasound (IVUS) parameters of the infarct-related artery for consecutive prospectively included patients.', 'Clinical, qualitative, and quantitative angiographic and IVUS data for 64 patients (56 men, aged 53+/-12 years) with thrombolysis of AMI were analyzed. All patients underwent coronary angiography and pre-interventional IVUS measurement electively within 1 month of AMI or at the time of the occurrence of postinfarction angina pectoris. Classification as adaptive or constrictive remodeling was according to whether the cross-sectional area of a vessel was larger or smaller than that of the proximal or distal reference segment.', 'Nineteen of the 64 patients (29.7%) suffered from recurrence of ischemic events (group 1), whereas 45 patients (60.3%, group 2) remained free from symptoms. In univariate analyses, multivessel disease (42 versus 24%, P= 0.0236) and adaptive remodeling (63 versus 24%, P= 0.0032) were found to occur more commonly among patients in group 1. The patients in group 1 exhibited larger total vessel cross-sectional areas than did the patients in group 2 (17.5+/-4.2 versus 14.9+/-6.1 mm2, P = 0.0556). In multivariate regression analysis, adaptive remodeling proved to be a significant predictor (P = 0.0145) of the recurrence of ischemic events after thrombolysis of AMI.'] |
['Molecular classifications defining new tumor subtypes have been recently refined with genetic and transcriptomic analyses of benign and malignant hepatocellular tumors. Here, we performed microRNA (miRNA) profiling in two series of fully annotated liver tumors to uncover associations between oncogene/tumor suppressor mutations and clinical and pathological features. Expression levels of 250 miRNAs in 46 benign and malignant hepatocellular tumors were compared to those of 4 normal liver samples with quantitative reverse-transcriptase polymerase chain reaction. miRNAs associated with genetic and clinical characteristics were validated in a second series of 43 liver tumor samples and 16 nontumor samples. miRNA profiling unsupervised analysis classified samples in unique clusters characterized by histological features (tumor/nontumor, P < 0.001; benign/malignant tumors, P < 0.01; inflammatory adenoma and focal nodular hyperplasia, P < 0.01), clinical characteristics [hepatitis B virus (HBV) infection, P < 0.001; alcohol consumption, P < 0.05], and oncogene/tumor suppressor gene mutations [beta-catenin, P < 0.01; hepatocyte nuclear factor 1alpha (HNF1alpha), P < 0.01]. Our study identified and validated miR-224 overexpression in all tumors and miR-200c, miR-200, miR-21, miR-224, miR-10b, and miR-222 specific deregulation in benign or malignant tumors. Moreover, miR-96 was overexpressed in HBV tumors, and miR-126* was down-regulated in alcohol-related hepatocellular carcinoma. Down-regulations of miR-107 and miR-375 were specifically associated with HNF1alpha and beta-catenin gene mutations, respectively. miR-375 expression was highly correlated to that of beta-catenin-targeted genes as miR-107 expression was correlated to that of HNF1alpha in a small interfering RNA cell line model. Thus, this strongly suggests that beta-catenin and HNF1alpha could regulate miR-375 and miR-107 expression levels, respectively.'] |
['Cellular senescence is a state of irreversible growth arrest shown by normal cells, and has been most extensively studied in replicative senescence caused by telomere shortening. Several conditions, including oncogenic Ras over-expression and inappropriate culture conditions, also induce senescence without telomere shortening. However, it remains unclear how a common set of senescence phenotypes is indistinguishably induced in various types of senescence.', 'We demonstrate that p38 mitogen-activated protein kinase (MAPK) plays important causative roles in senescent cells following telomere shortening, Ras-Raf activation, oxidative stress or inappropriate culture conditions. By monitoring the kinetics of p38 activation, we suggest that p38 is activated not directly by the initial stimuli, but in response to unidentified cellular conditions caused by these stimuli. Importantly, this p38-activating condition appears to be defined quantitatively as a sum of continuous and low-level stresses, and remains even after the initial stimuli are withdrawn, which may explain the well-known irreversible nature of cellular senescence. We also show that papilloma virus E7 abolishes the p38-induced growth arrest but not other senescence-associated phenotypes, indicating the differential role of pRb in the downstream of p38.'] |
['To see whether transient myocardial ischaemia on ambulatory monitoring after myocardial infarction is associated with ventricular arrhythmias.', 'A prospective study.', 'The coronary care unit, general medical wards, and cardiorespiratory department of a major teaching hospital.', '203 consecutive patients without specific exclusion criteria admitted with acute myocardial infarction.', '24 hour ambulatory electrocardiographic monitoring for ventricular arrhythmias and ST depression both early (mean 6.3 days after infarction, n = 201) and late (mean 38 days, n = 177).', 'Episodes of myocardial ischaemia were identified during ambulatory monitoring by transient ST depression of > or = 1.0 mm lasting for > or = 30 s. Ventricular arrhythmias were single extrasystoles, couplets, or ventricular tachycardia.', 'All ventricular arrhythmias were significantly more frequent in late than early monitoring. The arrhythmias included couplets (in 83/174 (48%) v 49/200 (25%) of patients, p = 0.0000028) and ventricular tachycardia (29/174 (17%) v 15/199 (8%), p = 0.0064). Patients with ST depression (29 early; 56 late), compared with those without ischaemia, did not experience a significant increase in single extrasystoles, couplets (31% v 23% early; 47% v 48% late), or ventricular tachycardia (3% v 8% early; 18% v 16% late). Even patients with frequent (> or = 3 episodes), and deep (> or = 1.5 mm) or prolonged (> or = 20 min) ST depression had no increase in arrhythmias.'] |
['An association of language impairment with neonatal brachial plexus palsy has not been reported in the literature. The current treatment paradigm for neonatal brachial plexus palsy focuses on upper extremity motor recovery with little formal assessment of other aspects of development, such as language. We performed a cross-sectional pilot study to investigate early language delay prevalence in toddlers with neonatal brachial plexus palsy and potential neonatal brachial plexus palsy-related factors involved.', 'Twenty toddlers with neonatal brachial plexus palsy were consecutively recruited (12 males and eight females; mean age, 30 months). Preschool Language Scale Score (4th edition), demographics, and socioeconomic status were collected. Neonatal brachial plexus palsy-related factors such as palsy side, treatment type, Narakas grade, muscle Medical Research Council score, and Raimondi hand score were reported. Student t test, chi-square test, or Fisher exact test were applied. Statistical significance level was established at P < 0.05.', 'Of study participants, 30% had language delay, whereas the prevalence of language delay in the population with normal development in this age range was approximately 5-15%.'] |
['The study purpose was to evaluate sleep structure during ketogenic diet (KD) treatment in children with therapy-resistant epilepsy and to correlate possible alterations with changes in clinical effects on seizure reduction, seizure severity, quality of life (QOL), and behavior.', "Eighteen children were examined with ambulatory polysomnographic recordings initially and after 3 months of KD treatment. Eleven children continued with the KD and were also evaluated after 12 months. Sleep parameters were estimated. Seizure frequency was recorded in a diary and seizure severity in the National Health Seizure Severity Scale (NHS3). QOL was assessed with a visual analogue scale. Child behavior checklist and Ponsford and Kinsella's rating scale of attentional behavior were used.", 'KD induced a significant decrease in total sleep (p = 0.05) and total night sleep (p = 0.006). Slow wave sleep was preserved, rapid eye movement (REM) sleep increased (p = 0.01), sleep stage 2 decreased (p = 0.004), and sleep stage 1 was unchanged. Eleven children continued with the KD and were also evaluated after 12 months. They showed a significant decrease in daytime sleep (p = 0.01) and a further increase in REM sleep (p = 0.06). Seizure frequency (p = 0.001, p = 0.003), seizure severity (p < 0.001, p = 0.005) and QOL (p < 0.001, p = 0.005) were significantly improved at 3 and 12 months. Attentional behavior was also improved, significantly so at 3 months (p = 0.003). There was a significant correlation between increased REM sleep and improvement in QOL (Spearman r = 0.6, p = 0.01) at 3 months.'] |
['To investigate if markers of iron body stores and hemoglobin are associated with retinal vascular caliber.', 'This was a population-based study including 2993 participants of the fifth and sixth surveys of the Tromsø Study in Norway, conducted in 2001-2002 and 2007-2008. The association between levels of s-ferritin, transferrin saturation, and hemoglobin in the fifth survey and retinal vascular caliber in the sixth survey was assessed by multivariable linear regression models.', 'Men had higher levels of hemoglobin and s-ferritin than women. Hemoglobin was associated with wider retinal venules in both men and women (mean difference between highest compared to lowest sex-specific quartile: men 5.99 μm, P = 0.001; women 7.28 μm, P < 0.001). S-ferritin was associated with wider retinal venules in men but not women, independent of traditional risk factors (mean difference between highest compared to lowest sex-specific quartile: men 4.21 μm, P = 0.013; women -0.21 μm, P = 0.89). The association in men was attenuated, but still significant, with adjustment for hemoglobin. S-ferritin and level of hemoglobin were not associated with arteriolar caliber in either sex. Transferrin saturation was not associated with retinal vascular caliber.'] |
['Immobilized cervical spine, because of either diseases or stabilizing devices, poses considerable difficulties with endotracheal intubation due to poor laryngoscopic view. The left molar (LM) approach has been shown to be useful in difficult sporadic intubation cases. We evaluated efficacy of this approach of laryngoscopy to improve laryngeal view in patients with simulated limitation of cervical movements.', 'Thirty patients of American Society of Anesthesiologists grade I/II, who were scheduled to undergo routine surgical procedures under general anaesthesia and endotracheal intubation, were studied. A two-piece semi-rigid cervical collar was used to immobilize the cervical spine. Under standardized anaesthesia and neuromuscular blocking agent, conventional laryngoscopy using a curved Macintosh blade was performed and glottic view was recorded with and without optimal external laryngeal manipulation (OELM). Subsequently, in the same subjects the laryngoscope blade was withdrawn and re-inserted through the LM approach and glottic view was recorded with and without OELM followed by tracheal intubation.', 'With the conventional approach, laryngeal view was recorded as grade II in five patients, grade III in 24 patients, and grade IV in one patient. However, with the LM approach, laryngeal view was grade I in 25 patients, grade II in five patients, and grade III or IV in none (P<0.001). Tracheal intubation with the LM approach required the use of a flexible stylet to guide the tube tip into the larynx.'] |
[': Few epidemiological studies have examined the relationship between age at menopause and stroke incidence, and none have done so in Japanese women. Here, we investigated the relationship between age at menopause and stroke incidence in a large group of Japanese women.', ': The study participants were 4,790 postmenopausal women aged 36 to 89 years enrolled in the Jichi Medical School Cohort Study, a population-based prospective study. Baseline data were obtained by questionnaire and health checkups between April 1992 and July 1995 in 12 rural areas in Japan. The incidence of all strokes and stroke subtypes was monitored.', ': Mean (SD) participant age was 61.0 (6.7) years, and mean (SD) age at menopause was 48.3 (4.8) years. A total of 185 strokes were observed during a mean follow-up of 10.8 years. On adjustment for age, systolic blood pressure, total cholesterol, body mass index, smoking habits, and alcohol drinking habits, hazard ratios (95% CIs) of stroke for women who underwent menopause before age 40 years, at 40 to 44 years, at 45 to 49 years, and at 55 years or after relative to those who underwent menopause at age 50 to 54 years were 1.56 (0.78-3.12), 1.59 (1.00-2.51), 1.28 (0.92-1.78), and 0.83 (0.38-1.81), respectively. However, hazard ratios (95% CI) of cerebral infarction for women who underwent menopause before age 40 years, at 40 to 44 years, at 45 to 49 years, and at 55 years or after relative to those who underwent menopause at age 50 to 54 years were 2.57 (1.20-5.49), 1.49 (0.80-2.78), 1.06 (0.67-1.68), and 1.08 (0.43-2.74), respectively.'] |
['This study evaluates the effect of zoledronic acid (ZOL) on the osseointegration of titanium implants in rabbits with glucocorticoid (GC)-induced bone loss, and our findings demonstrated that a single dose of ZOL is able to reverse the detrimental effects of GCs on the osseointegration of titanium implants.', 'The purpose of this study is to evaluate the effect of ZOL on the osseointegration of titanium implants in rabbits with GC-induced bone loss.', 'Three groups of six NZW rabbits were treated for 18 weeks with saline (SALINE), GC (methylprednisolone, 0.35 mg/kg three times a week), or GC + ZOL (methylprednisolone + single dose of ZOL, 0.1 mg/kg). The animals received a titanium implant in the left tibia after 6 weeks and were killed at the 18th week. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry at baseline, eighth week (W8), and 18th week (W18) after treatment to determine the change upon treatment (BMD). Histomorphometric and serum bone alkaline phosphatase analysis (BAP) were also performed.', 'At W8, GC group had a significant reduction in lumbar spine and tibia BMD compared with SALINE (p = 0.003 and p = 0.000), as also observed for GC + ZOL group (p = 0.014 and p = 0.003) just 2 weeks after ZOL treatment. In contrast, at W18, the GC + ZOL had an evident BMD rescue with similar lumbar spine and tibia BMD compared with SALINE (0.043 +/- 0.006 vs. 0.055 +/- 0.009 g/cm(2), p = 0.457 and 0.027 +/- 0.003 vs. 0.041 +/- 0.011 g/cm(2), p = 0.232) and a significantly higher BMD compared with the GC (p = 0.024 and p = 0.001). Histomorphometry revealed that osseointegration was significantly reduced in GC (tibia cortical thickness and diameter, bone-implant contact, total and peri-implant bone area) whereas GC + ZOL had these parameters similar to SALINE (p > 0.05). Likewise, ZOL reversed the BAP alteration induced by GC.'] |
['Type I interferons (IFN) have been shown to play an important role for inhibiting Dengue virus (DENV) infection. Identifying IFN-induced cellular proteins are essential for understanding its mechanisms against DENV. Here we established stable Huh7-derived cell lines expressing the IFN-induced cell membrane protein BST2 (Huh7-BST2) or its variant bearing a V5 tag at the C-terminal (Huh7-BST5CV5). These cell lines were infected with DENV to determine proteins modulating their anti-DENV response. We found that expression of BST2 did not affect the efficiency of DENV infection and intracellular replication. Rather, it significantly reduced the virion yield of the infected cells, particularly at low MOI infection. In addition, BST2 also decreased the foci formation and the size of infectious foci in cultured Huh7 monolayers with media containing methocellulose. The addition of the V5 tag at C-terminal inhibited the GPI modification of BST2 and blocked its shift from endoplasm to cytoplastic membrane. BST2CV5 did not affect DENV infection and foci formation in Huh7 cells but reduced virion yield by 1 log at low MOI infection. Interestingly, intracellular BST2CV5 expression was reduced by high level of DENV production.'] |
['Our objective was to evaluate the association of arterial (18)F-FDG uptake and calcifications in large arteries as detected by (18)F-FDG PET/CT with the subsequent occurrence of vascular events in otherwise asymptomatic cancer patients.', 'Clinical follow-up information was obtained for 932 cancer patients examined with whole-body (18)F-FDG PET/CT (median follow-up time, 29 mo). Among this cohort, 279 patients had died from their oncologic disease. In 15 of 932 patients (1.6%), a vascular event, defined as ischemic stroke, myocardial infarction, or revascularization, was registered. The maximal standardized uptake value (SUV) was divided by the blood-pool SUV, yielding a target-to-background ratio (TBR) for each arterial segment. The mean TBR as well as a calcified plaque sum score per patient were calculated in the major vessels: ascending, descending, and abdominal aorta, aortic arch, as well as iliac and carotid arteries.', 'A significant correlation was observed between mean TBR and calcified plaque sum (P < 0.001). Although calcified plaque sum significantly correlated with all conventional risk factors for vascular events, mean TBR correlated only with age, the male sex, and hypertension. The Cox regression hazard model identified a mean TBR >or= 1.7 and a calcified plaque sum >or= 15 as independent predictors for the occurrence of a vascular event. Patients with both mean TBR and calcified plaque sum above these thresholds were identified as having the highest risk for a future vascular event. However, a mean TBR >or= 1.7 had greater prognostic value than did a calcified plaque sum >or= 15.'] |
['we investigated the relationship between sublingual perfused capillary density (PCD) as a measure of tissue perfusion and outcome (i.e. occurrence of organ failure and mortality) in patients with cardiogenic shock from acute myocardial infarction.', 'we performed a prospective study in 68 patients. Using Sidestream Dark Field imaging, PCD was measured after hospital admission (T0, baseline) and 24 h later (T1). We compared patients with baseline PCD ≤ median to patients with baseline PCD > median. Sequential organ failure assessment (SOFA) scores were calculated at both time points. The Kaplan-Meier 30-day survival analyses were performed and predictors of 30-day mortality were identified. The baseline PCD was a predictor of the change in the SOFA score between T0 and T1 (ΔSOFA; ρ = -0.25, P = 0.04). Organ failure recovered more frequently in patients with PCD > median (>10.3 mm mm(-2); n = 33) than in patients with PCD ≤ median (n = 35; 52 vs. 29%, P < 0.05). Twenty-two patients (32%) died: 17 patients (49%) with PCD ≤ median vs. 5 patients (15%) with PCD > median (P = 0.004). After adjustment, the cardiac power index [odds ratio (OR): 0.48, 95% CI: 0.24-0.94) and PCD (OR: 0.65, 95% CI: 0.45-0.92) remained significant predictors of 30-day outcome. Patients with baseline sublingual PCD ≤ median that improved at T1 had a considerable better prognosis relative to patients who had a persistently low PCD.'] |
['Diadenosine polyphosphates are normally present in cells at low levels, but significant increases in concentrations can occur during cellular stress. The aim of this study was to investigate the effects of diadenosine pentaphosphate (Ap5A) and an oxidized analogue, oAp5A on the gating of sheep cardiac ryanodine receptors (RyR2).', 'RyR2 channel function was monitored after incorporation into planar bilayers under voltage-clamp conditions.', "With10 micromol.L(-1) cytosolic Ca2+, a significant 'hump' or plateau at the base of the dose-response relationship to Ap5A was revealed. Open probability (Po) was significantly increased to a plateau of approximately 0.2 in the concentration range 100 pmol x L(-1)-10 micromol x L(-1). High Po values were observed at >10 micromol x L(-1) Ap5A, and Po values close to 1 could be achieved. Nanomolar levels of ATP and adenosine also revealed a hump at the base of the dose-response relationships, although GTP did not activate at any concentration, indicating a common, high-affinity binding site on RyR2 for adenine-based compounds. The oxidized analogue, oAp5A, did not significantly activate RyR2 via the high-affinity binding site; however, it could fully open the channel with an EC(50) of 16 micromol.L(-1) (Ap5A EC(50) = 140 micromol x L(-1)). Perfusion experiments suggest that oAp5A and Ap5A dissociate slowly from their binding sites on RyR2."] |
['Controversy exists regarding the causative role of dietary fructose in obesity and fatty liver diseases. Clinical trials have indicated that negative health consequences may occur only when fructose is consumed within excess calories. Animal studies have suggested that fructose impairs intestinal integrity and leads to hepatic steatosis (HS).', 'We assessed nonhuman primates after chronic ad libitum and short-term calorically controlled consumption of a high-fructose (HFr), low-fat diet (24% of calories). Microbial translocation (MT), microbiome, and metabolic health indexes were evaluated.', 'Seventeen monkeys fed 0.3–7 y of an HFr ad libitum diet were compared with 10 monkeys fed a low-fructose, low-fat diet (control). Ten middle-aged, weight-stable, fructose-naive monkeys were stratified into HFr and control groups fed for 6 wk at caloric amounts required to maintain weight stability. Metabolic endpoints, feces, liver, small and large intestinal biopsies, and portal blood samples were collected.', 'Monkeys allowed ad libitum HFr developed HS in contrast to the control diet, and the extent of ectopic fat was related to the duration of feeding. Diabetes incidence also increased. Monkeys that consumed calorically controlled HFr showed significant increases in biomarkers of liver damage, endotoxemia, and MT indexes and a trend for greater hepatitis that was related to MT; however, HS did not develop.'] |
['Casparian bands are characteristic of the endodermis and exodermis of roots, but also occur infrequently in other plant organs, for example stems and leaves. To date, these structures have not been detected in phellem cells of a periderm. The aim of this study was to determine whether Casparian bands occur in phellem cells using tests that are known to detect Casparian bands in cells that also contain suberin lamellae. Both natural periderm and wound-induced structures were examined in shoots and roots.', 'Using Pelargonium hortorum as a candidate species, the following tests were conducted: (1) staining with berberine and counterstaining with aniline blue, (2) mounting sections in concentrated sulphuric acid and (3) investigating the permeability of the walls with berberine as an apoplastic, fluorescent tracer.', '(1) Berberine-aniline blue staining revealed a modification in the radial and transverse walls of mature phellem cells in both stems and roots. Three days after wounding through to the cortex of stems, the boundary zone cells (pre-existing, living cells nearest the wound) had developed vividly stained primary walls. By 17 d, staining of mature phellem cells of wound-induced periderm was similar to that of natural periderm. (2) Mature native phellem cells of stems resisted acid digestion. (3) Berberine was excluded from the anticlinal (radial and transverse) walls of mature phellem cells in stems and roots, and from the wound-induced boundary zone.'] |
['Mortality and morbidity in patients with bacterial meningitis result from the proinflammatory response and dysregulation of coagulation and fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) is activated by free thrombin or thrombin in complex with thrombomodulin, and plays an antifibrinolytic role during fibrin clot degradation, but also has an anti-inflammatory role by inactivating proinflammatory mediators, such as complement activation products.', 'To assess the role of TAFI in pneumococcal meningitis.', 'We performed a prospective nationwide genetic association study in patients with bacterial meningitis, determined TAFI and complement levels in cerebrospinal fluid (CSF), and assessed the function of TAFI in a pneumococcal meningitis mouse model by using Cpb2 (TAFI) knockout mice.', 'Polymorphisms (reference sequences: rs1926447 and rs3742264) in the CPB2 gene, coding for TAFI, were related to the development of systemic complications in patients with pneumococcal meningitis. Higher protein levels of TAFI in CSF were significantly associated with CSF complement levels (C3a, iC3b, and C5b-9) and with more systemic complications in patients with bacterial meningitis. The risk allele of rs1926447 (TT) was associated with higher levels of TAFI in CSF. In the murine model, consistent with the human data, Cpb2-deficient mice had decreased disease severity, as reflected by lower mortality, and attenuated cytokine levels and bacterial outgrowth in the systemic compartment during disease, without differences in the brain compartment, as compared with wild-type mice.'] |
['Musculoskeletal (MSK) conditions are common, and their burden on the healthcare system is increasing as the general population ages. It is essential that medical students be well prepared to evaluate and treat MSK disorders in a confident manner as they enter the workforce. Recent studies and the American Association of Medical Colleges have raised concern that medical schools may not give sufficient instruction on this topic. Other authors have shown that preclinical instruction has increased over the past decade; however, it is unclear if required clinical instruction also has followed that trend.', 'The purposes of this study were: (1) to assess the presence and duration of required or selective instruction in a MSK medicine specialty within the clinical years of undergraduate medical education; and (2) to assess the current state of requirements of clinical clerkships or rotations in other surgical and nonsurgical fields for comparison with the initial findings.', "The web sites of all 141 US medical schools were assessed to determine the content of their clinical curricula for the 2014-2015 academic year; five were excluded because they had not yet had a graduating class by the conclusion of the 2014-2015 academic year. Complete information on required rotations was obtained through the schools' web sites for all 136 (100%) medical schools. For selective experience during the surgery clerkships, complete information was available for 130 of the remaining 136 (96%) web sites.", 'Mean (in weeks, ± SD) duration of core clerkships were as follows: internal medicine (10 ± 2), surgery (8 ± 2), pediatrics (7 ± 1), obstetrics/gynecology (6 ± 1), and psychiatry (5 ± 1). Other common required clerkships were: family medicine (required in 96% [131 of 136] of schools, mean duration of 6 ± 2 weeks), neurology (81% [110], 4 ± 1), and emergency medicine (55% [75], 3 ± 1). Required MSK instruction, at a mean of 2 ± 1 weeks, was only present in 15% (20 of 136) of medical schools. In addition, clinical MSK instruction was offered as a selective (eg, students pick from a selection of subspecialties such as orthopaedics, plastics, or urology during a general surgery clerkship) in 34% (44 of 130) of all medical schools. This is less than other non-core specialties: geriatrics/ambulatory care (required in 40% [54 of 136] of schools, mean duration of 3 ± 1 weeks), critical care (30% [41], mean of 3 ± 1 weeks), radiology (26% [35], mean of 3 ± 1 weeks), anesthesiology (23% [31], mean of 2 ± 1 weeks), and other surgical subspecialties (19% [26], mean of 3 ± 1weeks).'] |
['Although inhaled glucocorticoids are the mainstays of asthma treatment, they are poorly effective at treating and preventing virus-induced asthma exacerbations. The major viruses precipitating asthma exacerbations are rhinoviruses.', 'We sought to evaluate whether rhinovirus infection interferes with the mechanisms of action of glucocorticoids.', 'Cultured primary human bronchial or transformed (A549) respiratory epithelial cells were infected with rhinovirus 16 (RV-16) before dexamethasone exposure. Glucocorticoid receptor (GR) α nuclear translocation, glucocorticoid response element (GRE) binding, and transactivation/transrepression functional readouts were evaluated by using immunocytochemistry, Western blotting, DNA binding assays, real-time quantitative PCR, coimmunoprecipitation, and ELISA techniques. Specific inhibitors of c-Jun N-terminal kinase (JNK) and of IκB kinase (IKK) were used to investigate the involvement of intracellular signaling pathways.', 'RV-16 infection impaired dexamethasone-dependent (1) inhibition of IL-1β-induced CXCL8 release, (2) induction of mitogen-activated protein kinase phosphatase 1 gene expression, and (3) binding of GR to GREs in airway epithelial cells. This was associated with impaired GRα nuclear translocation, as assessed by means of both immunochemistry (54.0% ± 6.8% vs 24.7% ± 3.8% GR-positive nuclei after 10 nmol/L dexamethasone treatment in sham- or RV-16-infected cells, respectively; P < .01) and Western blotting. RV-16 infection induced nuclear factor κB activation and GRα phosphorylation, which were prevented by inhibitors of IKK2 and JNK, respectively. In rhinovirus-infected cells the combination of JNK and IKK2 inhibitors totally restored dexamethasone suppression of CXCL8 release, induction of mitogen-activated protein kinase phosphatase 1 gene expression, and GRα nuclear translocation.'] |
['Pancreatic beta-cell mass expands through adulthood under certain conditions. The related molecular mechanisms are elusive. This study was designed to determine whether surviving (also known as Birc5), which is transiently expressed perinatally in islets, was required for beta-cell mass expansion in the pancreatic duct-ligated mouse model.', 'Mice with beta cell-specific deletion of survivin (RIPCre(+)survivin(fl/fl)) and their control littermates (RIPCre(+)survivin(+/+)) were examined to determine the essential role of survivin in partial pancreatic duct ligation (PDL)-induced beta-cell proliferation, function and survival.', 'Resurgence of survivin expression occurred as early as day 3 post-PDL. By day 7 post-PDL, control mice showed significant expansion of beta-cell mass and increase in beta-cell proliferation and islet number in the ligated tail of the pancreas. However, mice deficient in beta-cell survivin showed a defect in beta-cell mass expansion and proliferation with a marked attenuation in the increase of total islet number, largely due to an impairment in the increase in number of larger islets while sparing the increase in number of small islets in the ligated tail of pancreas, resulting in insufficient insulin secretion and glucose intolerance. Importantly however, beta cell neogenesis and apoptosis were not affected by the absence of survivin in beta cells after PDL.'] |
['To determine the psychometric properties of an adapted version of the Falls Efficacy Scale (FES) in older rehabilitation patients.', 'Cross-sectional survey.', 'Postacute rehabilitation facility in Switzerland.', 'Seventy elderly persons aged 65 years and older receiving postacute, inpatient rehabilitation.', 'Not applicable.', "FES questions asked about subject's confidence (range, 0 [none]-10 [full]) in performing 12 activities of daily living (ADLs) without falling. Construct validity was assessed using correlation with measures of physical (basic ADLs [BADLs]), cognitive (Mini-Mental State Examination [MMSE]), affective (15-item Geriatric Depression Scale [GDS]), and mobility (Performance Oriented Mobility Assessment [POMA]) performance. Predictive validity was assessed using the length of rehabilitation stay as the outcome. To determine test-retest reliability, FES administration was repeated in a random subsample (n=20) within 72 hours.", 'FES scores ranged from 10 to 120 (mean, 88.7+/-26.5). Internal consistency was optimal (Cronbach alpha=.90), and item-to-total correlations were all significant, ranging from .56 (toilet use) to .82 (reaching into closets). Test-retest reliability was high (intraclass correlation coefficient, .97; 95% confidence interval, .95-.99; P<.001). Subjects reporting a fall in the previous year had lower FES scores than nonfallers (85.0+/-25.2 vs 94.4+/-27.9, P=.054). The FES correlated with POMA (Spearman rho=.40, P<.001), MMSE (rho=.37, P=.001), BADL (rho=.43, P<.001), and GDS (rho=-.53, P<.001) scores. These relationships remained significant in multivariable analysis for BADLs and GDS, confirming FES construct validity. There was a significant inverse relationship between FES score and the length of rehabilitation stay, independent of sociodemographic, functional, cognitive, and fall status.'] |
['Previously, we demonstrated that neonatal isolation increases acquisition of cocaine self-administration in adult male rats.', 'Now we examine whether neonatal isolation enhances maintenance and cocaine-induced reinstatement of extinguished self-administration behavior. To test the specificity of the effect, a separate study examined maintenance of food responding.', 'Litters were subjected to neonatal isolation (individual isolation; 1 h/day; postnatal days 2-9) or were non-handled. In experiment 1, adult male rats trained to self-administer cocaine (0.5 mg/kg per infusion; fixed-ratio 3 or FR3) were tested under fixed and progressive ratio (PR) schedules with different cocaine doses (0.125-1.0 mg/kg per infusion). After cocaine self-administration was extinguished, cocaine (0.5 or 2 mg/kg)-induced reinstatement of responding was assessed. In experiment 2, responding for food under an FR15 and two PR schedules were assessed in separate groups of neonatally isolated and non-handled male rats.', 'Neonatally isolated rats responded for low cocaine doses at higher rates and infused more cocaine relative to non-handled rats under both FR and PR schedules. However, there are no group differences in cocaine-induced reinstatement or in responding for food under the PR schedules. However, neonatally isolated rats lever pressed for food at lower rates under the FR schedule.'] |
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