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['Oxidative stress is an important causative factor in atherosclerosis. Isoprostanes are derivatives of arachidonate oxidized by reactive oxygen species (ROS). Oxidized lipids are markers of oxidative stress, important mediators of atherosclerosis, and activators of platelets. 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) is a stable isoprostane and reliable marker of oxidative stress in vivo.', 'The aim of the study was to determine the level of oxidative stress in acute coronary syndromes (ACS) and its correlations with the para meters of hemo stasis.', 'Fourty-nine patients aged 46 to 76 years, including 28 with ACS and 25 with stable coronary artery disease (CAD), were enrolled to the study. The levels of 8-iso-PGF2alpha, soluble CD40 ligand (sCD40L), P-selectin (P-sel), beta-thromboglobulin, and the thrombin-antithrombin complex (TAT) in the plasma of venous blood were determined. A microvascular injury model was also used to evaluate TAT generation and sCD40L levels in blood collected every 60 seconds at the site of standardized microvascular injury.', '8-iso-PGF2alpha levels were significantly higher in ACS compared to CAD patients (363.2 +/-45.94 vs. 328.2 -/+31.96 pg/ml, P = 0.011) and correlated with venous plasma levels of P-sel and beta-thromboglobulin in the ACS (r = 0.66; P = 0.0005 and r = 0.62; P = 0.001, respectively) and CAD groups (r = 0.46; P = 0.02 and r = 0.49; P = 0.01, respectively). In the microvascular injury model, the maximum concentrations of sCD40L in the ACS group were associated with plasma 8-iso-PGF2alpha levels (r = 0.50, P = 0.01). No correlations between 8-iso-PGF2alpha and markers of thrombin generation in venous blood and microvascular injury model were observed.'] |
['Animal models have demonstrated that maternal undernutrition or early gestation glucocorticoid exposure induces endothelial dysfunction in the offspring.', 'We sought to determine whether early gestation dexamethasone (DEX) exposure is further associated with increased vascular superoxide anion production.', "DEX (0.28 mg/kg/day i.v. for 48 h) was administered to pregnant ewes at 27-28 days' gestation (term 145 days). Tissues were harvested from DEX-exposed and control lambs at 125 days' gestation (n = 6 for each group) and 4 months following delivery (n = 9 and 12, respectively).", 'By lucigenin-enhanced chemiluminescence, coronary and mesenteric arteries from DEX-exposed fetuses exhibited diminished basal superoxide production (both p < 0.01). Similarly, DEX-exposed carotid arteries from 4-month-old lambs had decreased superoxide production (p < 0.01) that localized to the endothelium by endothelial cell culture and dihydroethidium fluorescence. In contrast, DEX-exposed coronary arteries from the 4-month-old sheep had increased superoxide production (p < 0.05). Although early gestation DEX exposure did not alter lipid peroxidation, DEX exposure was associated with significantly increased renal and cerebral cortex aconitase activity (consistent with decreased protein oxidation). These changes occurred in the absence of alterations in renal cortex superoxide dismutase activity.'] |
['High frequency oscillatory ventilation (HFOV) improves gas exchange while providing lung protective effects during the ventilation of patients with the acute respiratory distress syndrome (ARDS). The purpose of this study was to review our experience with HFOV in adult burn patients with oxygenation failure secondary to ARDS.', 'Retrospective cohort review of all burn patients treated with HFOV at a regional adult burn center.', 'All values are reported as the mean +/- standard deviation (S.D.). HFOV was used on 28 occasions in 25 patients (age 44 +/- 16 years, %TBSA burns 40 +/- 15, and a 28% incidence of inhalation injury) who had severe oxygenation failure from ARDS (PaO2/FiO2 ratio 98 +/- 26, and oxygenation index (OI) (FiO2 x 100 x mean airway pressure/PaO2) 27 +/- 10) following 4.8 +/- 4.4 days of conventional mechanical ventilation (CMV). After switching from CMV to HFOV, there were significant improvements in the PaO(2)/FiO2 ratio within 1h and in the oxygenation index within 24 h. The duration of HFOV was 6.1 +/- 5.8 days. HFOV was continued during 26 surgeries for 14 patients where a mean of 18 +/- 9% TBSA burns were excised and closed. The only complications related to HFOV were three episodes of severe hypercapnia. In-hospital mortality was 32%.'] |
['Teeth are often included in the radiation field during head and neck radiotherapy, and recent clinical evidence suggests that dental pulp is negatively affected by the direct effects of radiation, leading to impaired sensitivity of the dental pulp. Therefore, this study aimed to investigate the direct effects of radiation on the microvasculature, innervation, and extracellular matrix of the dental pulp of patients who have undergone head and neck radiotherapy.', 'Twenty-three samples of dental pulp from patients who finished head and neck radiotherapy were analyzed. Samples were histologically processed and stained with hematoxylin-eosin for morphologic evaluation of the microvasculature, innervation, and extracellular matrix. Subsequently, immunohistochemical analysis of proteins related to vascularization (CD34 and smooth muscle actin), innervation (S-100, NCAM/CD56, and neurofilament), and extracellular matrix (vimentin) of the dental pulp was performed.', 'The morphologic study identified preservation of the microvasculature, nerve bundles, and components of the extracellular matrix in all studied samples. The immunohistochemical analysis confirmed the morphologic findings and showed a normal pattern of expression for the studied proteins in all samples.'] |
['Retrograde coronary venous infusion is a promising delivery method for cellular cardiomyoplasty. Poor cell retention is the major obstacle to the establishment of this method as the preferred route for cell delivery. Here, we explored whether magnetic targeting could enhance retrograde cell retention in a rat model of myocardial infarction.', 'Rat mesenchymal stem cells were labeled with superparamagnetic oxide nanoparticles. The magnetic responsiveness of MSCs was observed while cells flowed through a tube that served as a model of blood vessels in a 0.6-Tesla magnetic field. In a Sprague–Dawley rat model of acute myocardial infarction, 1\u2009×\u2009106 magnetic mesenchymal stem cells were transjugularly injected into the left cardiac vein while a 0.6-Tesla magnet was placed above the heart. The cardiac retention of transplanted cells was assessed by using quantitative Y chromosome-specific polymerase chain reaction, cardiac magnetic resonance imaging, and optical imaging. Cardiac function was measured by using echocardiography, and histologic analyses of infarct morphology and angiogenesis were obtained.', 'The flowing iron oxide-labeled mesenchymal stem cells were effectively attracted to the area where the magnet was positioned. Twenty-four hours after cellular retrocoronary delivery, magnetic targeting significantly increased the cardiac retention of transplanted cells by 2.73- to 2.87-fold. Histologic analyses showed that more transplanted cells were distributed in the anterior wall of the left ventricle. The enhanced cell engraftment persisted for at least 3 weeks, at which time, left ventricular remodeling was attenuated, and cardiac function benefit was improved.'] |
['Renal cell carcinoma in a renal graft is a rare condition whose incidence will increase in the future. To our knowledge no standardized treatment has been established for this disease. We performed a prospective study of nephron sparing surgery for small renal cell carcinoma in renal grafts.', 'From January 2002 to December 2006, 2,050 renal graft recipients were followed at our transplantation center. Of these patients 7 were diagnosed with histologically confirmed renal cell carcinoma in the renal graft, 5 of whom presented with T1a renal cell carcinoma and prospectively underwent nephron sparing surgery.', 'Five patients with 15 to 30 mm (median 20) renal cell carcinoma were included in the study and were treated with nephron sparing surgery. Median operative time was 110 minutes (range 60 to 150). Blood loss was less than 200 ml in each case. All tumors were pT1aN0M0 with negative margins. No postoperative complications were observed (hemorrhage, urinary fistulas, renal failure). Preoperative immunosuppressive treatment was not modified postoperatively. At 3 months after nephron sparing surgery and at a mean of 17.4 months of followup (range 5 to 54) no significant impairment of renal function or recurrence was observed.'] |
['Commencing antiretroviral therapy (ART) in human immunodeficiency virus-infected patients with treated or unrecognized Mycobacterium tuberculosis disease may trigger tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) or ART-associated tuberculosis (ART-TB). We have shown that whole-blood interferon-gamma release assays may aid in the prediction and diagnosis of ART-TB. Here, we investigate interferon-gamma-inducible chemokines CXCL9 and CXCL10.', 'CXCL9 and CXCL10 responses to region of difference 1 (RD1) antigens and purified protein derivative (PPD) were assayed in plasma from whole-blood cultures collected before and after 4, 12, and 24 weeks of ART from 15 TB-IRIS cases, 11 ART-TB cases, and matched controls.', 'Relative to matched controls, ART-TB cases had elevated CXCL10 responses to RD1 antigens pre-ART (P = 0.02) and to PPD and RD1 antigens over 24 weeks of ART (P ≤ 0.02 and P ≤ 0.03). In contrast, TB-IRIS cases had higher CXCL10 responses to RD1 antigens before and after 4 weeks of ART only (P = 0.04 for both). CXCL9 responses to PPD and RD1 antigens were similar but less pronounced in ART-TB cases and did not differ between TB-IRIS cases and controls. CXCL10 responses to RD1 antigens performed as well as, or better than, IFN-γ responses in the prediction and diagnosis of ART-TB.'] |
['To demonstrate that occipital nerve injury is associated with chronic postoperative headache in patients who have undergone acoustic neuroma excision and to determine whether occipital nerve excision is an effective treatment for these headaches.', 'Few previous reports have discussed the role of occipital nerve injury in the pathogenesis of the postoperative headache noted to commonly occur following the retrosigmoid approach to acoustic neuroma resection. No studies have supported a direct etiologic link between the two. The authors report on a series of acoustic neuroma patients with postoperative headache presenting as occipital neuralgia who were found to have occipital nerve injuries and were treated for chronic headache by excision of the injured nerves.', 'Records were reviewed to identify patients who had undergone surgical excision of the greater and lesser occipital nerves for refractory chronic postoperative headache following acoustic neuroma resection. Primary outcomes examined were change in migraine headache index, change in number of pain medications used, continued use of narcotics, patient satisfaction, and change in quality of life. Follow-up was in clinic and via telephone interview.', 'Seven patients underwent excision of the greater and lesser occipital nerves. All met diagnostic criteria for occipital neuralgia and failed conservative management. Six of 7 patients experienced pain reduction of greater than 80% on the migraine index. Average pain medication use decreased from 6 to 2 per patient; 3 of 5 patients achieved independence from narcotics. Six patients experienced 80% or greater improvement in quality of life at an average follow-up of 32 months. There was one treatment failure. Occipital nerve neuroma or nerve entrapment was identified during surgery in all cases where treatment was successful but not in the treatment failure.'] |
['Hepatocellular carcinoma (HCC) has high mortality and no adequate treatment. Endocannabinoids interact with hepatic cannabinoid 1 receptors (CB1Rs) to promote hepatocyte proliferation in liver regeneration by inducing cell cycle proteins involved in mitotic progression, including Forkhead Box M1. Because this protein is highly expressed in HCC and contributes to its genesis and progression, we analyzed the involvement of the endocannabinoid/CB1R system in murine and human HCC. Postnatal diethylnitrosamine treatment induced HCC within 8 months in wild-type mice but fewer and smaller tumors in CB1R(-/-) mice or in wild-type mice treated with the peripheral CB1R antagonist JD5037, as monitored in vivo by serial magnetic resonance imaging. Genome-wide transcriptome analysis revealed CB1R-dependent, tumor-induced up-regulation of the hepatic expression of CB1R, its endogenous ligand anandamide, and a number of tumor-promoting genes, including the GRB2 interactome as well as Forkhead Box M1 and its downstream target, the tryptophan-catalyzing enzyme indoleamine 2,3-dioxygenase. Increased indoleamine 2,3-dioxygenase activity and consequent induction of immunosuppressive T-regulatory cells in tumor tissue promote immune tolerance.'] |
['Well-controlled studies have demonstrated that inpatient hyperglycemia is an indicator of poor clinical outcomes, but the use of diabetes-specific enteral formulas in hospitalized patients remains a topic of great debate.', 'In two different protocols, postprandial glycemia and insulinemia were measured in 22 subjects with diabetes fed a diabetes-specific or standard formula (protocol 1). Continuous glucose monitoring was used to assess glucose levels in 12 enterally fed patients with diabetes receiving the standard formula followed by the diabetes-specific formula continuously for 5 days each (protocol 2). End points included postprandial glycemia and insulinemia, glycemic variability (mean amplitude of glycemic excursions [MAGE]), mean glucose, and insulin use.', 'In the postprandial response protocol, the diabetes-specific formula resulted in lower positive areas under the postprandial curve (P < 0.001) and peak glucose (P < 0.001) and insulin (P = 0.017) levels. In the protocol using continuous glucose monitoring, glycemic variability (as measured by MAGE) was lower with continuous administration of the diabetes-specific than the standard formula (64.6 +/- 6.8 mg/dL vs. 110.6 +/-15.3 mg/dL, P = 0.003). Also, administration of the diabetes-specific formula resulted in lower mean glucose concentrations during feeding (171.1 +/- 16.1 vs. 202.1 +/- 17.4 mg/dL, P = 0.024) and insulin requirements (7.8 +/- 2.3 vs. 10.9 +/- 3.3 units/day, P = 0.039) than the standard formula.'] |
['Many complications have been reported to occur with surgery for scoliosis in Prader-Willi Syndrome (PWS). However, growth hormone (GH) treatment has contributed to improvements in height, body composition, bone density and breathing functions in PWS patients. The purpose of this study was to investigate patients who underwent surgery for scoliosis in PWS.', 'There were 136 PWS patients being followed-up by the Pediatrics Department of our hospital. Among these, we investigated nine patients who had undergone surgery. Their mean age was 11 years. The mean follow-up period was 6 years 10 months.', 'The mean body mass index was 22.5 kg/m(2). GH therapy was administered to eight patients. Brace treatment was performed in two patients. Spinal correction and fusion were performed in six patients, and the growing rod method was performed in three patients. Necessary reoperations were performed in two patients. For the total 11 surgeries in the nine patients, the mean blood loss was 397 ml and the mean operation time was 4 h and 20 min. The mean Cobb angles were 76.0 degrees preoperatively and 35.8 degrees at follow-up. Regarding complications, one patient experienced early dislodgment of the hook and one patient experienced a superior wound infection.'] |
['Activated Stat3 is an important mediator of oncogenesis in the colon. To test the hypothesis that select Stat activation and/or the pattern of Stat activation serves as a marker for early neoplastic transformation, we examined the distribution of activated Stat1(pStat1), Stat6(pStat6), and Stat3(pStat3) in colitis along the continuum of inactive disease to colitis-associated cancer.', "Tissue microarrays were constructed using colonoscopy biopsy and surgical specimens from 67 patients with ulcerative colitis or Crohn's colitis and 11 controls. In all, 111 sets of samples were analyzed representing normal tissue, active disease, low-grade dysplasia, high-grade dysplasia, and colitis-associated cancer. Immunohistochemistry to detect pStat1, pStat6, and pStat3 in colonic epithelial and mucosal immune cells was then correlated with clinical and pathological data (tumor location, histologic type, grade, and lymph node involvement).", 'In 50% of colitis-associated cancer samples, pStat3 was detected prominently in epithelial cells, where it was routinely associated with intense pStat3 staining in surrounding immune cells. Stat3 activation was greater in low-grade tumors than in high-grade ones (P < 0.05). pStat6 expression was more common in normal tissues than in colitis-associated cancer (P < 0.05). pStat1 was detected in a small subset of immune cells in patients with chronic inactive and active colitis, low- and high-grade dysplasia, but not in colitis-associated cancer.'] |
['To study the production of aggrecanase 1 (ADAM-TS4) in monolayer chondrocytes, capsular fibroblasts, and cartilage.', 'Bovine nasal and articular cartilage, monolayer chondrocytes, and capsular fibroblasts were incubated in the absence and presence of interleukin-1 (IL-1). ADAM-TS4 production was evaluated by immunofluorescence or by Western blot analysis. Aggrecanase activity was measured in cells grown on an immobilized peptide substrate, and peptide cleavage was monitored by enzyme-linked immunosorbent assay.', 'There was constitutive production of ADAM-TS4 in both cells and tissue. The protein was associated with the extracellular matrix based on the observation that the staining could be reduced following treatment of chondrocytes with heparin or exposure to chondroitinase ABC. Interestingly, there was no detectable change in the abundance of ADAM-TS4 in response to IL-1. Western blot analysis of cell lysates from IL-1-stimulated chondrocytes showed no evidence of increased ADAM-TS4 production, but resulted in activation of ADAM-TS4. The activation was associated with an increased generation in the aggrecanase neoepitope NITEGE in nasal cartilage in response to IL-1. These data suggest that induction of aggrecanase activity both in cells and in cartilage by IL-1 may involve the stimulation of an activator of ADAM-TS4. Consistent with this observation, culture of chondrocytes on a solid support containing a peptide substrate resulted in the generation of aggrecanase-mediated cleavage that could be blocked by selective inhibitors of ADAM-TS4.'] |
['Angelica Sinensis (AS), a folk medicine, has long been used in ergogenic aids for athletes, but there is little scientific evidence supporting its effects. We investigated whether AS induces hypertrophy in myotubes through the phosphatidylinositol 3-kinase (PI3K)/Akt (also termed PKB)/mammalian target of the rapamycin (mTOR) pathway.', 'An in vitro experiment investigating the induction of hypertrophy in myotubes was conducted. To investigate whether AS promoted the hypertrophy of myotubes, an established in vitro model of myotube hypertrophy with and without AS was used and examined using microscopic images. The role of the PI3K/Akt/mTOR signaling pathway in AS-induced myotube hypertrophy was evaluated. Two inhibitors, wortmannin (an inhibitor of PI3K) and rapamycin (an inhibitor of mTOR), were used.', 'The results revealed that the myotube diameters in the AS-treated group were significantly larger than those in the untreated control group (P\u2009<\u20090.05). Wortmannin and rapamycin inhibited AS-induced hypertrophy. Furthermore, AS increased Akt and mTOR phosphorylation through the PI3K pathway and induced myotube hypertrophy.'] |
['Cytomegalovirus establishes lifelong persistency in the host and leads to life threatening situations in immunocompromised patients. FoxP3+ T regulatory cells (Tregs) critically control and suppress innate and adaptive immune responses. However, their specific role during MCMV infection, especially pertaining to their interaction with NK cells, remains incompletely defined.', 'To understand the contribution of Tregs on NK cell function during acute MCMV infection, we infected Treg depleted and undepleted DEREG mice with WT MCMV and examined Treg and NK cell frequency, number, activation and effector function in vivo.', 'Our results reveal an increased frequency of activated Tregs within the CD4+ T cell population shortly after MCMV infection. Specific depletion of Tregs in DEREG mice under homeostatic conditions leads to an increase in NK cell number as well as to a higher activation status of these cells as compared with non-depleted controls. Interestingly, upon infection this effect on NK cells is completely neutralized in terms of cell frequency, CD69 expression and functionality with respect to IFN-γ production. Furthermore, composition of the NK cell population with regard to Ly49H expression remains unchanged. In contrast, absence of Tregs still boosts the general T cell response upon infection to a level comparable to the enhanced activation seen in uninfected mice. CD4+ T cells especially benefit from Treg depletion exhibiting a two-fold increase of CD69+ cells 40 h and IFN-γ+ cells 7 days p.i. while, MCMV infection per se induces robust CD8+ T cell activation which is also further augmented in Treg-depleted mice. Nevertheless, the viral burden in the liver and spleen remain unaltered upon Treg ablation during the course of infection.'] |
['Recent studies have shown that human papillomavirus (HPV) is associated with a certain subset of head and neck squamous cell carcinoma (HNSCC)-namely, those arising in the oropharynx. The objective of this study is to determine the efficacy, detection, and genotype of high-risk (HR) HPV using the Roche cobas 4800 system (Roche Molecular System, Pleasanton, CA).', 'Forty-two fine-needle aspirate (FNA) specimens from 37 patients with cervical (n = 36) or mediastinal (n = 5) lymphadenopathy or a left parapharyngeal mass (n =1) were included in this prospective study. HR-HPV testing was performed on residual FNA material after direct smear preparation and, if positive, was further delineated into HPV 16/18 genotypes using the Roche cobas 4800 system. Follow-up included review of histologic material and/or electronic health records.', 'Among those HNSCCs that were positive for HR-HPV, 18 (100%) of 18 originated from the oropharynx, whereas only two (13%) of 15 HR-HPV-negative HNSCCs originated from the oropharynx (χ(2) test, P < .05). p16 immunohistochemical assay and HPV 16 in situ hybridization on corresponding histologic specimens were concordant with cytologic HR-HPV results.'] |
['Viral load testing for cytomegalovirus (CMV) is an important diagnostic tool for the management of transplant recipients and immunocompromised individuals; however, inconsistency among laboratories in quantitative measurements of viral load limits interinstitutional comparisons. These inconsistencies stem from the lack of assays cleared by the US Food and Drug Administration, the absence of international standards, the wide variety of CMV-extraction and -detection methods, and differences in materials used for calibration. A critical component of standardization is the use of calibrators that are traceable and commutable.', 'Bland-Altman plots and prediction ellipses were used to test the commutability of 2 CMV calibrators for 2 different quantification methods.', 'Tests with 2 methods showed 1 calibrator to be commutable and the other to be noncommutable. The results for the commutable calibrator were within the 95% prediction interval of the clinical samples in the Bland-Altman plot and within the 95% prediction ellipse for a simulated commutable calibrator, whereas the results for the noncommutable calibrator were not within these prediction intervals. When used to calibrate patient results, only the commutable calibrator, the OptiQuant CMV(tc) Calibration Panel, significantly improved the comparability of viral loads for the 2 different measurement methods.'] |
['Velopharyngeal insufficiency and chronic otitis media with effusion following primary cleft palate repair can be attributed to persistent abnormalities in the levator and tensor veli palatini muscles, respectively. The purpose of this case-control study was to examine the association between otitis media with effusion requiring myringotomy tubes and the need for secondary speech surgery.', "Records of patients who underwent primary palatoplasty at the authors' institution from 1990 to 2006 were reviewed. Data included age at primary palatoplasty, sex, Veau classification, surgeon, number of postpalatoplasty myringotomy tube procedures, hearing loss, 22q deletion syndrome diagnosis, and fistula. The primary outcome was need for secondary speech surgery.", 'Of 249 patients meeting inclusion criteria, forty-four patients (17.7 percent) had secondary speech surgery recommended or performed. Univariate analysis revealed a significant association between Veau classification, 22q deletion syndrome diagnosis, and two or more myringotomy tube procedures with secondary speech surgery. Adjusting for multiple covariates, children requiring two or more myringotomy tubes were 2.55 times more likely to require secondary speech surgery than patients who required one or fewer myringotomy tubes procedures (95 percent CI, 1.24 to 5.21; p = 0.009).'] |
['Cerebral small vessel disease is one of the most important risk factors for dementia, and has been related to hippocampal atrophy, which is among the first observed changes on conventional MRI in patients with dementia. However, these volumetric changes might be preceded by loss of microstructural integrity of the hippocampus for which conventional MRI is not sensitive enough. Therefore, we investigated the relation between the hippocampal diffusion parameters and the risk of incident dementia, using diffusion tensor imaging, independent of hippocampal volume.', 'The RUNDMC study is a prospective study among 503 elderly with small vessel disease, without dementia, with 5 years follow-up in 2012 (99.6% response-rate). Cox regression analysis was performed to calculate hazard ratios for dementia, of fractional anisotropy and mean diffusivity within the hippocampus, adjusted for demographics, hippocampal volume, and white matter. This was repeated in participants without evident hippocampal volume loss, because in these participants the visible damage might not yet have already started, whereas damage might have started on a microstructural level.', '43 participants developed dementia (8.6%), resulting in a 5.5-year cumulative risk of 11.1% (95%CI 7.7-14.6). Higher mean diffusivity was associated with an increased 5-year risk of dementia. In the subgroup of participants with the upper half hippocampal volume, higher hippocampal mean diffusivity, more than doubled the 5-year risk of dementia.'] |
['The aim of this study was to investigate the prognostic significance of elevated white blood cell (WBC) count at the time of the diagnosis of cervical cancer recurrence.', 'The baseline characteristics and outcome data of 219 patients who had a diagnosis of recurrent cervical cancer between April 1996 and September 2010 were collected and reviewed. Survival after recurrence was compared between the leukocytosis group (WBC ≥9000/μL) and the nonleukocytosis group (WBC <9000/μL). A Cox proportional hazards regression model was used to investigate the prognostic significance of elevated WBC count in patients with recurrent cervical cancer.', 'The patients in the leukocytosis group showed significantly shorter disease-free interval (P = 0.0005) and more frequently had multiple recurrences (P = 0.0101) than those in the nonleukocytosis group. The median survival after recurrence of the patients with elevated WBC count was 9 months, which was significantly shorter than the 21 months observed in the patients without normal WBC count (log rank; P < 0.0001). Multivariate analyses revealed that clinical stage, tumor diameter, histology, an elevated WBC count (≥9000/μL), and an elevated neutrophil count (≥6500/μL) were significant prognostic factors in survival after recurrence.'] |
['To evaluate the prognostic value of interocular amplitude ratio of flicker electroretinogram (ERG) in determining the development of neovascularization in patients with central retinal vein occlusion (CRVO).', 'We retrospectively reviewed the data obtained from flicker ERG in 51 CRVO patients. Of these, 22 eyes which had enough follow-up to differentiate ischemic CRVO from nonischemic CRVO were included for data analysis. The flicker ERG was recorded at a 30 Hz frequency after dark adaptation, and ten sweeps were averaged.', 'Eleven eyes were ischemic and 11 eyes were nonischemic. Three amplitude parameters had the potential to explain the type of CRVO. They were amplitude of lesion eye (p = 0.0001), interocular difference of amplitude (p < 0.0001), and interocular ratio of amplitude (p < 0.0001). Both an interocular amplitude difference of -23 microV and interocular amplitude ratio of 60% were very good cutoff points to differentiate ischemic from nonischemic CRVO. Receiver operating characteristic curve analysis revealed that each of the two cutoff values had a sensitivity and specificity of 100%.'] |
['Urothelial carcinoma has recently been shown to express several aquaporins (AQP), with AQP3 being of particular interest as its expression is reduced or lost in tumours of higher grade and stage. Loss of AQP3 expression was associated with worse progression-free survival (PFS) in patients with pT1 bladder cancer. The objective of this study was to investigate the prognostic value of AQP3 expression in patients with muscle-invasive bladder carcinoma (MIBC).', 'Retrospective single-centre analysis of the oncological outcome of patients following radical cystectomy (Cx) due to MIBC. Immunohistochemistry was used to assess AQP3 protein expression in 100 Cx specimens. Expression levels of AQP3 were related to clinicopathological variables. The impact of biomarker expression on progression-free, cancer-specific and overall survival was determined by multivariate Cox regression analysis (MVA).', 'High expression of AQP3 by the tumour was associated with a statistically significantly improved PFS (75 vs. 19 %, p = 0.043) and CSS (75 vs. 18 %, p = 0.030) and, alongside lymph node involvement, was an independent predictor of PFS (HR 2.871, CI 1.066-7.733, p = 0.037), CSS (HR 3.325, CI 1.204-8.774, p = 0.019) and OS (HR 2.001, CI 1.014-3.947) in MVA.'] |
['The use of dietary supplements has been increasing rapidly in Korea over the last decade. The aim of this study was to investigate associations between the pattern of dietary supplement use and the sociodemographic/lifestyle characteristics of Korean consumers.', 'Participants were asked to complete a self-administered questionnaire on their sociodemographic and lifestyle characteristics, perceived health status, and regular dietary supplement use.', 'A total of 697 men and 832 women completed the questionnaire. Of the respondents, 44.3% of the men and 53.2% of the women used some kind of dietary supplement regularly. Dietary supplement users were more likely to be women (P < 0.001), to be older than 50 years (P < 0.001), to have a higher household income (P = 0.003), to engage in moderate or vigorous physical activity (P < 0.032), to perceive themselves as healthy (P = 0.026), and to have received a diagnosis of a chronic disease (P < 0.001). In addition, the type of dietary supplements used varied with respect to sociodemographic and lifestyle factors. Among dietary supplement users, men preferred ginseng, and older respondents were more likely to use carbohydrate supplements and less likely to use lipid supplements. Those who had a lower BMI, were ex-smokers, or were nondrinkers preferred either vitamins or minerals. Those who were highly physical active or were nondrinkers tended to prefer either vitamin/mineral complexes or carbohydrate supplements.'] |
['Allergen challenge results in an immediate reduction in exhaled nitric oxide (FE(NO)) followed by a long-term increase. To study mast cell activation in relation to nitric oxide (NO), the study investigated the effect of inhaled adenosine monophosphate (AMP) as a mast cell activator and mast cell stabilizer - nedocromil sodium - on FE(NO). The NO synthase (NOS) iso-enzyme involved was studied by the NOS inhibitor aminoguanidine.', 'A double-blind, placebo-controlled, cross-over study was performed in two parts. Part I: eight atopic asthmatic subjects inhaled nedocromil or placebo before the AMP challenge. Spirometry and FE(NO) were measured at intervals over a 24-h period. Part II: seven subjects inhaled aminoguanidine before an identical protocol was used, as in Part I.', 'Part I: AMP challenge caused a significant decrease from baseline FE(NO)[placebo, 28.9 (20.3-37.4)%, P < 0.002 and nedocromil, 20.9 (8.2-33.6)%, P < 0.01]. Nedocromil gave partial protection against this decrease in FE(NO). The time-FE(NO) curve (AUC(0-24)) differed significantly between nedocromil and placebo: 2.7% (-3.6 to -9) vs. -6.6% (-12 to -1.3) FE(NO) changes h(-1), P < 0.002, respectively. Nedocromil protected against AMP-induced bronchoconstriction (AMP PC(20)) [nedocromil 182 (72.5-291) mg mL(-1) vs. placebo 21.7 (10.7-33) mg mL(-1), P < 0.002]. Part II: nebulized aminoguanidine resulted in a significant reduction in FE(NO) from baseline and was greater than after AMP alone (P = 0.006). Nedocromil increased AMP PC(20), but no longer protected against the late decrease in FE(NO).'] |
['To determine whether American ginseng (Panax Quinquefolium) confers antioxidant protection to postmenopausal women at rest and after a mild aerobic exercise session.', 'In this double-blinded parallel study, 12 female subjects (age range 55-75) consumed two capsules, containing 500 mg of dry American ginseng whole-root powder, everyday for 4 months, whereas 13 female control subjects of the same age range consumed two placebo capsules. Before and after the supplementation regimen each subject performed 30 minutes of treadmill walking on a 5% grade incline at an estimated 60% of VO(2)max.', 'Ginseng supplementation had no effect on heart rate, blood pressure, plasma blood glucose, or lactate concentration at rest or immediately after exercise tests. The ginseng supplemented group displayed a higher resting plasma glutathione disulfide (GSSG) concentration and lower glutathione (GSH):GSSG ratio, as well as a lower resting total antioxidant content (TAC). Plasma GSSG concentration decreased, whereas the GSH:GSSG ratio and TAC increased after exercise in all subjects. Furthermore, plasma malondialdehyde and urine 8-hydroxydeoxyguanosine concentrations were elevated in the ginseng-supplemented group. Erythrocyte superoxide dismutase and GSH reductase activities were increased after ginseng supplementation. The 30-minute treadmill walking, however, did not alter these changes.'] |
['Biomass fuels are used for cooking in the majority of rural households worldwide. While their use is associated with an increased risk of lung diseases and all-cause mortality, the effects on cardiovascular disease (CVD) are not well characterised. Exposure to biomass fuel smoke has been associated with lung-mediated inflammation and oxidative stress, which may increase the risk of atherosclerosis as evaluated by carotid intima-media thickness (CIMT), carotid atherosclerotic plaque prevalence and blood pressure.', 'A cross-sectional study was performed in 266 adults aged ≥35 years in Puno, Peru (3825 m above sea level). We stratified participants by their long-term history of exposure to clean fuel (n=112) or biomass fuel (n=154) and measured 24 h indoor particulate matter (PM2.5) in a random subset (n=84). Participants completed questionnaires and underwent a clinical assessment, laboratory analyses and carotid artery ultrasound. The main outcome measures were CIMT, carotid plaque and blood pressure.', 'The groups were similar in age and gender. The biomass fuel group had greater unadjusted mean CIMT (0.66 vs 0.60 mm; p<0.001), carotid plaque prevalence (26% vs 14%; p=0.03), systolic blood pressure (118 vs 111 mm Hg; p<0.001) and median household PM2.5 (280 vs 14 µg/m(3); p<0.001). In multivariable regression, the biomass fuel group had greater mean CIMT (mean difference=0.03 mm, 95% CI 0.01 to 0.06; p=0.02), a higher prevalence of carotid plaques (OR=2.6, 95% CI 1.1 to 6.0; p=0.03) and higher systolic blood pressure (mean difference=9.2 mm Hg, 95% CI 5.4 to 13.0; p<0.001).'] |
['12/15 lipoxygenase (12/15LO) has been implicated as a mediator of inflammation and atherosclerosis. In the current study, we identified mechanisms through which 12/15LO mediates monocyte:endothelial interactions in vivo in apolipoprotein E-deficient mice (apoEKO), a well-characterized mouse model of atherosclerosis.', 'In apoEKO mice that are also deficient in 12/15LO (doubleKO), monocyte adhesion to aorta in vivo was reduced by 95% in doubleKO mice compared with apoEKO mice. Inhibition of 12/15LO in apoEKO mice in vivo using CDC (Cinnamyl-3,4-Dihydroxy-a-Cyanocinnamate) prevented monocyte adhesion to aortic endothelium in apoEKO mice. Aortic endothelium of apoEKO mice had significant activation of rhoA compared with doubleKO aortic endothelium. Further, apoEKO aorta displayed significant activation of NF-kappaB. DoubleKO aorta displayed little nuclear localization of NF-kappaB. Finally, we found significant upregulation of intercellular adhesion molecule-1 (ICAM-1) on apoEKO aortic endothelium compared with doubleKO endothelium. Inhibition of rhoA and PKCalpha significantly reduced NF-kappaB activation, ICAM-1 induction, and monocyte adhesion to aorta.'] |
['Carcinoembryonic antigen (CEA) inhibits lymphocyte function and patients with cancer have lower cell-mediated immunity (CMI) than the normal population. To test this association an investigation was made of the relationship between CMI score, CEA level and survival.', 'CEA level, CMI score and other variables were compared with the survival time of 109 patients with colorectal liver metastases using Cox regression analysis.', 'There was a significant association between CMI and CEA categories (P = 0.04, chi 2 test). The odds of patients with normal CMI having a CEA level in the upper quartile observed for all patients were 22 per cent of those of patients with depressed CMI (odds ratio 0.22 (95 per cent confidence interval (c.i.) 0.03-0.90), mid-P corrected). The median survival time of patients with normal CMI scores was 943 days compared with 488 days for those with depressed CMI (P = 0.03, log rank test; P = 0.04, Peto). The mortality risk of patients with normal CMI at entry to the study was, in the first 2 years of treatment, 40 per cent of that of patients with depressed CMI (95 per cent c.i. for relative risk 0.20-0.82, Cox regression).'] |
['Oligonucleotide array and tissue microarray analysis (TMA) by our group has revealed that folate binding protein (FOLR1) is overexpressed in some types of uterine cancer, particularly tumors with serous histology. Since FOLR1 overexpression is a frequent event in some types of endometrial carcinoma, we examined the relationship between FOLR1 overexpression and clinical and pathologic features to determine its prognostic relevance.', 'A tissue microarray (TMA) comprised of primary tumor specimens from 485 patients diagnosed with endometrial adenocarcinoma was used to identify cases characterized by FOLR1 overexpression. A proportional hazards model was used to evaluate the association of FOLR1 overexpression with progression-free survival while accounting for confounding influences.', 'Overexpression of FOLR1 was observed in 50/292 (17%) cases and was seen more often in poorly differentiated cancers (22/90 [24%], p=0.051) and tumors with serous histology (16/32 [50%], p<0.001). A shorter progression-free survival was noted in patients with FOLR1 overexpression (log-rank p=0.016) that persisted when the data were limited to patients with stage III/IV disease (log-rank p=0.021) or serous tumors (log-rank p=0.020). Multivariate Cox regression analysis revealed that patients with FOLR1 overexpression had a shorter progression-free survival (H.R. 2.14; 95% CI 1.07-4.28) even when controlling for stage, grade, myometrial invasion and adjuvant chemotherapy.'] |
["Acidic diets are advocated as main risk factor for tooth erosion, which could be prevented, or at least controlled, if patients were early advised. It is important to identify, hence, if possible dietary constituents regionally consumed on large scale, such as tucupi, a low-pH yellowish-green color and strong flavor delicacy made from the juice of a bitter cassava, may explain its occurrence in specific patient groups. This cross-over in situ/ex vivo study evaluated tucupi's ability to promote erosion of bovine enamel by assessing its percentage of surface microhardness change (%SMHC), taking a cola-based soft drink and human saliva as positive and negative controls.", "For three 7-days spaced out legs of 7 days each, nine volunteers wore palatal devices with three bovine enamel blocks, which were challenged with one of the following solutions: TUC-tucupi (n=27); COL-cola-based soft drink (n=27); SAL-saliva (n=27). Erosive challenges were performed extra-orally (4×/day) by dropping TUC or COL at room temperature on specimens. After 5min, palatal devices were replaced into the mouth. SAL permanently acted as the negative control while volunteers solely wore the device. One-way ANOVA followed by Tukey's post-hoc tests (α=0.05) were applied.", 'TUC promoted an enamel %SMHC (-21.56±10.08(a)) similar than that promoted by COL (-18.19±12.99(a); p=0.275), which were both significantly higher than that promoted by SAL (-1.86±13.65(b); p<0.0001).'] |
['To profile the reactivity of CSF-derived immunoglobulin from patients with multiple sclerosis (MS) against a large panel of antigens, to identify disease-specific reactivities.', 'CSF from subjects with MS with elevated immunoglobulin G and CSF from control subjects presenting with other inflammatory neurologic disease were screened against a protein array consisting of 9,393 proteins. Reactivity to a candidate protein identified using these arrays was confirmed with ELISA and immunocytochemistry.', 'Autoantibodies against one protein on the array, recombination signal binding protein for immunoglobulin kappa J region (RBPJ), discriminated between patients with MS and controls (p = 0.0052). Using a large validation cohort, we found a higher prevalence of autoantibodies against RBPJ in the CSF of patients with MS (12.5%) compared with the CSF of patients with other neurologic diseases (1.6%; p = 0.02) by ELISA. This difference in reactivity was restricted to the CSF as serum reactivity against RBPJ did not differ between patients and controls. The presence of CSF autoantibodies against RBPJ was further confirmed by immunocytochemistry.'] |
["Vascular risk factors may be associated with disability independently of vascular events. We examined whether the American Heart Association's 7 ideal cardiovascular health (CVH) metrics were independently associated with disability in a nationally representative cohort.", 'Adults age ≥20 years from the National Health and Nutrition Examination Survey 2005-2012 were included. Ideal CVH was calculated as a composite of 7 measures, each scored 0-2. Primary predictors were number of ideal CVH metrics and score of CVH metrics. The outcome was a dichotomous score from 20 activities of daily living (ADL) and instrumental ADLs. Unadjusted and adjusted weighted logistic models estimated associations between ideal CVH and disability. The data were analyzed in 2015.', 'Among 22692 participants, mean age was 46.9 years. Cardiac disease and stroke were present in 6.6% and 2.8%; 90.3% had poor physical activity and 89.9% poor diet. Among 3975 individuals with full CVH data, in fully adjusted models, OR for disability was 0.90 (95% CI 0.83-0.98) per point increase in ideal CVH score, and 0.84 (0.73-0.97) per additional number of ideal CVH metrics.'] |
['The relevance of the cricothyroid (CT) muscle in patients with unilateral vocal fold paralysis (UVFP) remains controversial. To clarify the functional significance of the CT muscle in patients with UVFP, the confounding effect of the severity of recurrent laryngeal nerve injury should be taken into consideration. In the present study, quantitative laryngeal electromyography (LEMG) was used to measure the severity of paralysis of the thyroarytenoid-lateral cricoarytenoid (TA-LCA) muscle complex to allow the functional contribution of the CT muscle to be determined.', 'Cross-sectional study performed in an otolaryngology outpatient clinic.', 'Thirty-one patients with a main diagnosis of UVFP were recruited. The main outcome measures included LEMG examination, quantitative LEMG analysis of the TA-LCA muscle complex, UVFP-related quality-of-life questionnaire (Voice Outcome Survey [VOS]), voice acoustics analysis, videolaryngostroboscopy, and general quality-of-life questionnaire (Short Form-36 Health Survey [SF-36]) assessments.', 'The vocal cord position did not differ between patients with and without CT muscle impairment. Patients with both TA-LCA and CT paralysis showed poorer vocal fold vibration (P = .048) and higher fundamental frequency (P = .02), and the VOS and SF-36 were both poorer compared with patients with only TA-LCA paralysis.'] |
['The Bladder cooling reflex (BCR) i.e. uninhibited detrusor contractions evoked by intravesical instillation of cold saline, is a segmental reflex believed to be triggered by menthol sensitive cold receptors in the bladder wall, with the afferent signals transmitted by C fibres. The BCR is a neonatal reflex that becomes suppressed by descending signals from higher centres at approximately the time when the child gains full voluntary control of voiding. It re-emerges in adults with neurogenic detrusor overactivity as a consequence of loss of central descending inhibition, resulting from conditions such as spinal cord injury or multiple sclerosis. We have recently shown an increase of nerve fibres expressing the cool and menthol receptor TRPM8 in both overactive (IDO) and painful bladder syndrome (PBS), but its functional significance is unknown. We have therefore studied the bladder cooling reflex and associated sensory symptoms in patients with PBS and overactivity disorders.', 'The BCR, elicited by ice water test (IWT) was performed in patients with painful bladder syndrome (PBS, n = 17), idiopathic detrusor overactivity (IDO, n = 22), neurogenic detrusor overactivity (NDO, n = 4) and stress urinary incontinence (as controls, n = 21). The IWT was performed by intravesical instillation of cold saline (0 - 4 degrees C). A positive IWT was defined as presence of uninhibited detrusor contraction evoked by cold saline, associated with urgency or with fluid expulsion. Patients were asked to report and rate any pain and cold sensation during the test.', 'A positive IWT was observed in IDO (6/22, 27.3%) and NDO (4/4, 100%) patients, but was negative in all control and PBS patients. Thirteen (76.5%) PBS patients reported pain during the IWT, with significantly higher pain scores during ice water instillation compared to the baseline (P = 0.0002), or equivalent amount of bladder filling (100 mls) with saline at room temperature (P = 0.015). None of the control or overactive (NDO/IDO) patients reported any pain during the IWT.'] |
['The heart forms from a linear tube that is subject to complex remodeling during embryonic development. Hallmarks of this remodeling are the looping of the heart tube and the regionalization into chamber and non-chamber myocardium. Cardiomyocytes in the future chamber myocardium acquire different cellular and physiological characteristics through activation of a chamber-specific genetic program, which is in part mediated by T-box genes.', 'We characterize two new zebrafish T-box transcription factors, tbx3b and tbx2a, and analyze their role during the development of the atrioventricular canal. Loss- and gain-of-function analyses demonstrate that tbx3b and tbx2a are necessary to repress the chamber-genetic program in the non-chamber myocardium. We also show that tbx3b and tbx2a are required to control cell proliferation in the atrioventricular canal and that misregulation of cell proliferation in the heart tube influences looping. Furthermore, we characterize the heart phenotype of a novel Tbx3 mutation in mice and show that both the control of cell proliferation and the repression of chamber-specific genetic program in the non-chamber myocardium are conserved roles of Tbx3 in this species.'] |
['Ankylosing spondylitis (AS) is a chronic inflammatory disease with involvement of axial and sacroiliac joints. In addition, patients with AS have increased risk of cardiovascular disease (CVD), which might be attributed to enhanced inflammatory activity of the arterial wall. In the present study, we compared the level of carotid arterial wall inflammation in patients with AS with healthy controls using (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography with CT. As arterial wall inflammation is reduced by statin therapy, we subsequently assessed the effect of 3-month statin therapy on arterial wall inflammation in AS.', 'We included 24 patients with AS (age 44±10, 72% males) without a history of CVD and 20 controls matched for age and gender. Patients with AS had lower high-density lipoprotein cholesterol and increased C reactive protein (CRP) compared with controls. The 10-year CVD risk was 2% in both groups. Notwithstanding, patients with AS had a 20% increase in arterial wall (18)F-FDG uptake compared with controls. Three-month atorvastatin 40\u2005mg daily significantly lowered low-density lipoprotein cholesterol (baseline 3.55±1.15\u2005mmol/L, -53%) and CRP (baseline 5.0 (1.5-9.3) mg/L, -58%) with a concomitant decrease of carotid arterial wall inflammation (maximum target-to-background ratio from 1.90±0.30 to 1.67±0.27; p=0.009).'] |
['To investigate the protective effect of catalpol on cerebral ischaemia/reperfusion (CI/R) injury in gerbils and further explore the underlying mechanism.', 'A gerbil model of CI/R was prepared by bilateral common carotid occlusion for 10\u2009min followed by 6\u2009h reperfusion. Catalpol (5, 10 or 20\u2009mg/kg per day) was injected intraperitoneally for 3 days before the carotid occlusion. Stroke index was measured during the reperfusion. The contents of endogenous neuropeptides, endothelin-1 (ET-1) and calcitonin gene-related peptide in plasma were evaluated by radioimmunoassay. Superoxide dismutase (SOD) and malondialdehyde (MDA) in brain tissue homogenate were also examined.', 'The results showed that catalpol significantly improved the stroke index compared with CI/R control group (P\u2009<\u20090.05 or P\u2009<\u20090.01). Catalpol significantly increased the activity of SOD at the doses of 10 and 20\u2009mg/kg (P\u2009≤\u20090.05), decreased the brain MDA content and the plasma level of ET-1 at the doses of 10 and 20\u2009mg/kg (P\u2009≤\u20090.01).'] |
['To evaluate radiographic tumor control and treatment-related toxicity in glomus jugulare tumors treated with stereotactic radiosurgery (SRS).', 'Retrospective chart review.', 'Tertiary academic referral center.', 'Glomus jugulare tumors treated with SRS between 1998 and 2014 were identified. The data analysis only included patients with at least 18months of post-treatment follow up (FU).', 'Patients were treated with either single fraction or fractionated SRS.', 'Patient demographics and tumor characteristics were assessed. Radiographic control was determined by comparing pre and post treatment MRI, and was categorized as no change, regression, or progression.', 'Eighteen patients were treated with SRS, and 14 met inclusion criteria. Median age at treatment was 55years (range 35-79), and 71.4% of patients were female. 5 patients (35.7%) received single fraction SRS (dose range 15-18Gy), and 9 (64.3%) fractionated therapy (dose 3-7Gy×3-15 fractions). Median tumor volume was 3.78cm(3) (range 1.15-30.6). Median FU was 28.8months (range 18.6-56.1), with a mean of 31.7months. At their last recorded MRI, 7 patients (50%) had tumor stability, 6 (42.9%) had improvement, and 1 (7.1%) had progression. Disease improvement and progression rates in the single fraction group were 40% and 0%, and in the multiple-fraction group, 44.4% and 11.1%, respectively. There was no statistically significant difference in disease improvement (p=0.88) or progression (p=0.48) rates between groups (unpaired t-test).'] |
["The present study investigated how parents and peers interact in promoting or delaying Dutch adolescents' sexual initiation and intention and focused specifically on parents as moderators of peer influence.", "Using a longitudinal design, two waves of online questionnaire data were collected among 900 Dutch adolescents (M = 13.8 years at T1), who were sexually inexperienced at baseline. At T1, participants reported on three types of perceived sexual peer norms: friends' sexual behaviors (descriptive norms), friends' sexual attitudes (injunctive norms), and experienced peer pressure to have sex. They also rated two parenting aspects at T1: the general quality of their relationship with parents and the frequency of sexuality-specific communication with their parents. Six months later, the participants reported on their experience with different sexual behaviors ranging from naked touching or caressing to intercourse and their intention to have sex in the next school year.", "Relationship quality with parents was significantly associated with both outcomes, with a higher relationship quality predicting smaller odds of sexual initiation and less intention to have sex. Two significant interaction effects showed that frequent sexual communication with parents significantly reduced the effects of sexually active friends and experienced peer pressure on adolescents' intention to have sex."] |
['Dendritic cells (DCs) connect innate and adaptive immunity, and are necessary for an efficient CD4+ and CD8+ T cell response after infection with Mycobacterium tuberculosis (Mtb). We previously described the macrophage cell death response to Mtb infection. To investigate the effect of Mtb infection on human DC viability, we infected these phagocytes with different strains of Mtb and assessed viability, as well as DNA fragmentation and caspase activity. In parallel studies, we assessed the impact of infection on DC maturation, cytokine production and bacillary survival.', 'Infection of DCs with live Mtb (H37Ra or H37Rv) led to cell death. This cell death proceeded in a caspase-independent manner, and without nuclear fragmentation. In fact, substrate assays demonstrated that Mtb H37Ra-induced cell death progressed without the activation of the executioner caspases, 3/7. Although the death pathway was triggered after infection, the DCs successfully underwent maturation and produced a host-protective cytokine profile. Finally, dying infected DCs were permissive for Mtb H37Ra growth.'] |
['To determine the incidence and timing of new intraocular tumor foci in genetic retinoblastoma cases after treatment with ophthalmic artery chemosurgery (OAC).', 'Single-center retrospective review of all genetic retinoblastoma cases managed at Memorial Sloan-Kettering Cancer Center/Weil-Cornell Medical School since May 2006.', 'Eighty-one patients (80 with bilateral disease and 1 with unilateral disease with a family history) with genetic retinoblastoma, with a total of 116 eyes treated with OAC since May 2006.', 'Retrospective, single-institution review of patients with bilateral retinoblastoma and unilateral retinoblastoma with a positive family history. New tumors were assessed by clinical notes, retinal drawings, and RetCam digital imaging (Clarity Medical Systems, Pleasanton, CA).', 'New intraocular retinoblastoma tumors after treatment with OAC.', 'Forty-one eyes were treated primarily with OAC (treatment-naïve group) and 75 eyes were treated with OAC after prior treatment with systemic chemotherapy, external beam radiation, or both and focal techniques. Of the 41 treatment-naïve eyes, a new intraocular tumor (one focus) subsequently developed in 1 eye. Of the 75 previously treated eyes, new tumors (single focus in each eye) subsequently developed in 6 eyes.'] |
['Given the association between iron deficiency and lead absorption, we hypothesized that variants in iron metabolism genes would predict higher blood lead levels in young children.', 'We examined the association between common missense variants in the hemochromatosis (HFE) and transferrin (TF) genes and blood lead levels in 422 Mexican children.', "Archived umbilical cord blood samples were genotyped for HFE (H63D and C282Y) and TF (P570S) variants. Blood lead was measured at 24, 30, 36, 42, and 48 months of age. A total of 341 subjects had at least one follow-up blood lead level available and data available on covariates of interest for inclusion in the longitudinal analyses. We used random-effects models to examine the associations between genotype (HFE, TF, and combined HFE + TF) and repeated measures of blood lead, adjusting for maternal blood lead at delivery and child's concurrent anemia status.", 'Of 422 children genotyped, 17.7, 3.3, and 18.9% carried the HFE H63D, HFE C282Y, and TF P570S variants, respectively. One percent of children carried both the HFE C282Y and TF P570S variants, and 3% of children carried both the HFE H63D and TF P570S variants. On average, carriers of either the HFE (beta = 0.11, p = 0.04) or TF (beta = 0.10, p = 0.08) variant had blood lead levels that were 11% and 10% higher, respectively, than wild-type subjects. In models examining the dose effect, subjects carrying both variants (beta = 0.41, p = 0.006) had blood lead 50% higher than wild-type subjects and a significantly higher odds of having a blood lead level > 10 microg/dL (odds ratio = 18.3; 95% confidence interval, 1.9-177.1).'] |
['Autoimmune diseases have been implicated as a cause of intrinsic asthma; however, there is little data on the role of autoimmunity in the pathogenesis of asthma.', 'The purpose of this study was to investigate circulating functional autoantibodies against the high-affinity IgE receptor FcepsilonRI or IgE in patients with asthma.', 'Twenty-eight patients with asthma and 19 control subjects were included. All subjects were skin tested with autologous serum to assess for the potential presence of receptor FcepsilonRI or IgE autoantibodies. If the serum-induced wheal diameter was 1.5 mm larger than the histamine-induced wheal diameter and that was 3 mm larger than the saline-induced wheal diameter at 30 min, the reaction was defined positive.', 'Of the 47 total subjects (both asthma patients and control subjects), 13 (27.7%) had a positive autologous serum skin test (ASST). Of the 28 asthma patients, 8 (28.6%) were regarded as having autoimmune origin. Autoantibodies against FcepsilonRI or IgE were found in asthma patients, irrespective of atopic status (atopy+ 3/13 vs. atopy- 5/15). The wheal diameter related to ASST was not related to atopy. Asthma patients with ASST-positive results as compared with patients with ASST-negative results exhibited a significant increased airway hyperresponsiveness (PC(20) methacholine, 2.70 +/- 1.27 vs. 9.08 +/- 2.35; p < 0.026).'] |
['The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have activity in one of the pathways influenced by nitrogen-containing bisphosphonates, which are associated with improved survival in multiple myeloma (MM). To understand the benefit of statins in MM, we evaluated the association between statin use and mortality in a large cohort of patients with MM.', 'From the Veterans Administration Central Cancer Registry, we identified patients diagnosed with MM between 1999 and 2013. We defined statin use as the presence of any prescription for a statin within 3 months before or any time after MM diagnosis. Cox proportional hazards regression assessed the association of statin use with mortality, while controlling for known MM prognostic factors.', 'We identified a cohort of 4,957 patients, of whom 2,294 received statin therapy. Statin use was associated with a 21% decrease in all-cause mortality (adjusted hazard ratio, 0.79; 95% CI, 0.73 to 0.86; P < .001) as well as a 24% decrease in MM-specific mortality (adjusted hazard ratio, 0.76; 95% CI, 0.67 to 0.86; P < .001). This association remained significant across all sensitivity analyses. In addition to reductions in mortality, statin use was associated with a 31% decreased risk of developing a skeletal-related event.'] |
['Higher coffee and green tea consumption has been suggested to decrease risk of type 2 diabetes, but their roles in insulin resistance (IR) and insulin secretion remain unclear. This study examined the association between habitual consumption of these beverages and markers of glucose metabolism in a Japanese working population.', 'Participants were 1440 Japanese employees (1151 men and 289 women) aged 18-69years. Consumption of coffee and green tea was ascertained via a validated brief diet history questionnaire. Multilevel linear regression was used to estimate means (95% confidence intervals) of fasting insulin, fasting plasma glucose, homeostatic model assessment of IR (HOMA-IR), homeostatic model assessment of β-cell function (HOMA-β) and glycated hemoglobin (HbA1c) with adjustment for potential confounding variables.', 'Coffee consumption was significantly, inversely associated with HOMA-IR (P for trend=0.03), and the association appeared to be confined to overweight subjects (BMI≥25kg/m(2)) (P for trend=0.01, P for interaction=0.08). Unexpectedly, green tea consumption was positively associated with HOMA-IR (P for trend=0.02), though there was no dose-response relationship among daily consumers of green tea. Neither coffee nor green tea consumption was associated with HOMA-β and HbA1c.'] |
['To evaluate efficacy and safety on steroid withdrawal at the seventh day after liver transplantation.', 'Seventy-six adult patients undergoing first cadaveric liver transplantation from October 2005 to October 2007 were randomly divided into 7 day (n = 40) and 3 month (n = 36) steroid withdrawal groups. All patients received FK506 3 mg and intravenous methylprednisolone 1000 mg during intra-operation and FK506 thereafter was adjusted to predefined 8 - 12 microg/L from day 1 to month 6. Patients in 7 day steroid withdrawal group received 500, 240, 200, 160, 80, 40 and 20 mg intravenous methylprednisolone tapered daily from postoperative day 1 to day 7. In 3 month steroid withdrawal group, patients received the same protocol as 7 day steroid withdrawal group for intravenous methylprednisolone tapered daily from postoperative day 1 to day 7 and thereafter received oral prednisone 48, 40, 32, 24, 16, 8, 4 mg tapered every 3 days and maintained 4 mg to the 3(rd) month. All patients were followed up for 6 months. The incidence of treated acute rejection and side effects were evaluated between two groups.', 'A total of 69 cases were fully followed up, and 7 cases were discontinued including death (n = 2), server infection (n = 2), protocol violation (n = 2) and retransplantation (n = 1). There were no statistical difference between 2 groups concerning the incidence of acute rejection, hypertension, hyperlipemia and other adverse events (P > 0.05), but significant difference in incidence of diabetes (17.5% vs. 38.9%, P = 0.047).'] |
['LY450139 (semagacestat) inhibits gamma-secretase, a key enzyme for generation of amyloid beta (Abeta), the peptide deposited in plaques in Alzheimer disease (AD). Previous data have shown that LY450139 lowers plasma Abeta, but has no clear effect on Abeta1-40 or Abeta1-42 levels in cerebrospinal fluid (CSF). By using targeted proteomics techniques, we recently identified several shorter Abeta isoforms, such as Abeta1-16, that in experimental settings increase during gamma-secretase inhibitor treatment, and thus may serve as sensitive biochemical indices of the treatment effect. Here, we test the hypothesis that these shorter Abeta isoforms may be biomarkers of gamma-secretase inhibitor treatment in clinical trials.', 'In a phase II clinical trial, 35 individuals with mild to moderate AD were randomized to placebo (n = 10) or LY450139 (100 mg (n = 15) or 140 mg (n = 10)) and underwent lumbar puncture at baseline and after 14 weeks of treatment. The CSF Abeta isoform pattern was analyzed with immunoprecipitation combined with MALDI-TOF mass spectrometry.', 'The CSF levels of Abeta1-14, Abeta1-15, and Abeta1-16 showed a dose-dependent increase by 57% and 74%, 21% and 35%, and 30% and 67%, respectively in the 100-mg and 140-mg treatment groups. Abeta1-40 and Abeta1-42 were unaffected by treatment.'] |
['Sentinel lymph node (SLN) biopsy with the standard intraparenchymal injection has been accepted as an alternative to routine axillary dissection for patients with breast cancer. However, the identification and false-negative rates with this method can vary widely from surgeon to surgeon. The subareolar location contains a rich lymphatic network and represents a potential site of injection for SLN identification.', 'Between August 1, 1999, and December 31, 2000, we performed 159 SLN biopsy procedures on 158 patients with breast cancer. For each patient, 99mTc-labeled sulfur colloid was injected into the subareolar location, and 1% isosulfan blue dye was given as an intraparenchymal injection.', 'In every case, at least one radioactive SLN was identified with the subareolar injection of technetium; a blue SLN was found in 97% of the cases. The blue SLN was also radioactive in 98% of the cases, indicating that the blue dye injected around the tumor and the technetium injected into the subareolar location drained to the same SLN.'] |
['Obstructive sleep apnea is associated with cognitive impairment, but whether hypoxemia or repeated arousals and sleepiness are the underlying mechanism is controversial. Studies using a wide range of attention and executive functions tests in patients with severe sleep apnea are lacking.', "In a prospective cohort study, 40 patients aged 30-70 years, diagnosed with obstructive sleep apnea (apnea-hypopnea index ≥5) were recruited. Patients with known cardiovascular, pulmonary, psychiatric, or neurological disease, and or patients receiving anti-psychotic, sedatives, or stimulant medications were excluded. Patients underwent full overnight polysomnography including continuous oxygen saturation measurements followed by extensive neuropsychological testings in attention and executive function domains. The correlation between sleep apnea severity and patients' performance on the neuropsychological tests was examined.", "The patients' performance on measures of attention and executive function was significantly worse compared to the average in a normal population. Attention, as reflected by the number of omissions and by the reaction time on the Conners' Continuous Performance Test correlated significantly with the apnea-hypopnea index (r = 0.6, p < 0.001 and r = 0.48, p = 0.003, respectively) and with parameters of hypoxemia, namely the average SpO(2) (r = -0.51, p = 0.002 and r = -0.39, p = 0.02, respectively) and the percent time spent with SpO(2) < 90% (r = 0.57, p < 0.001 and r = 0.39, p = 0.02, respectively), but not with the degree of sleepiness. Executive dysfunction did not correlate with sleep parameters."] |
['The cellular immune response in gastric mucosa infected with Helicobacter pylori is proposed to be predominantly of the T helper cell type 1 type.', 'Interleukin (IL)-18, IL-12, and interferon (IFN)-gamma levels were measured in gastric mucosal biopsy specimens by reverse-transcription polymerase chain reaction (PCR) and by enzyme-linked immunosorbent assay; IL18 polymorphisms were determined by PCR.', 'Biopsy specimens from 128 patients (56 with nonulcer dyspepsia, 28 with gastric ulcers, 28 with duodenal ulcers, and 16 with gastric cancer) were examined; 96 patients had H. pylori infection. IL-18 levels were markedly up-regulated in mucosa infected with H. pylori (P < .001), whereas IL-12 and IFN-gamma levels were independent of H. pylori status. IL-18 levels correlated with IFN-gamma levels only in infected patients (R = 0.31 to R = 0.51). IL-18 levels were the determining factor for monocyte infiltration in H. pylori-infected mucosa (P < .001). H. pylori-infected patients displaying IL18 -607C/C and -137G/G had higher IL-18 levels than did those with other genotypes and were more likely to experience treatment failure.'] |
['Nuclear factor kappa-B (NF-954;B)-induced inflammation leads to myocarditis and heart dysfunction. How microRNAs (miRNAs) contribute to this process is poorly defined. The aim of this study was to investigate whether miRNAs regulate NF-954;B-induced inflammation in experimental autoimmune myocarditis (EAM) in vivo.', "NF-954;B and its related proinflammatory genes, including interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a), were activated in EAM. Profiling of NF-954;B-related miRNAs revealed that miR-590-3p was strikingly reduced in EAM. We found IL-6-induced proinflammatory signaling via miR-590-3p reduction, p50 induction, NF-954;B activation and IL-6/TNF-a expression. Moreover, a luciferase reporter assay demonstrated that miR-590-3p directly interacted with the 3' UTR (untranslated region) of the p50 subunit, and that miR-590-3p overexpression inhibited p50 expression. Finally, miR-590-3p transfection through adeno-associated virus significantly inhibited p50 expression, suppressed NF-954;B activity and blocked IL-6/TNF-a expression in vivo, reducing the lesion area and improving cardiac function in EAM."] |
['A new class of non-coding RNAs, known as long non-coding RNAs (lncRNAs), has been recently described. These lncRNAs are implicated to play pivotal roles in various molecular processes, including development and oncogenesis. Gene expression profiling of human B-ALL samples showed differential lncRNA expression in samples with particular cytogenetic abnormalities. One of the most promising lncRNAs identified, designated B-ALL associated long RNA-6 (BALR-6), had the highest expression in patient samples carrying the MLL rearrangement, and is the focus of this study.', 'Here, we performed a series of experiments to define the function of BALR-6, including several novel splice forms that we identified. Functionally, siRNA-mediated knockdown of BALR-6 in human B-ALL cell lines caused reduced cell proliferation and increased cell death. Conversely, overexpression of BALR-6 isoforms in both human and mouse cell lines caused increased proliferation and decreased apoptosis. Overexpression of BALR-6 in murine bone marrow transplantation experiments caused a significant increase in early hematopoietic progenitor populations, suggesting that its dysregulation may cause developmental changes. Notably, the knockdown of BALR-6 resulted in global dysregulation of gene expression. The gene set was enriched for leukemia-associated genes, as well as for the transcriptome regulated by Specificity Protein 1 (SP1). We confirmed changes in the expression of SP1, as well as its known interactor and downstream target CREB1. Luciferase reporter assays demonstrated an enhancement of SP1-mediated transcription in the presence of BALR-6. These data provide a putative mechanism for regulation by BALR-6 in B-ALL.'] |
['Nitrous oxide (N2O)-induced teratogenicity in rats is commonly believed to be due to decreased tetrahydrofolate, which results in decreased DNA synthesis. The role of decreased methionine has been largely ignored as have the sympathomimetic effects of N2O.', 'A rat whole-embryo culture system was used to determine whether N2O-induced teratogenicity can be prevented with supplemental methionine or folinic acid and whether N2O-induced situs inversus is mediated by alpha 1-adrenergic stimulation. Embryos were explanted on day 9 of gestation, and those at stage 10b (late primitive streak stage) were cultured with or without N2O and the various chemicals, methionine (25 micrograms.ml-1), folinic acid (5 micrograms.ml-1), phenylephrine (range 0.5-50 microM) and prazosin (10 microM). Embryos in the N2O groups were exposed to a concentration of 75% for the first 24 h of culture. After 50 h of culture, embryos were examined for abnormalities including situs inversus.', 'Treatment with N2O alone resulted in increased incidences of malformations and growth retardation. Methionine, but not folinic acid or prazosin, almost completely prevented N2O-induced malformations and growth retardation. N2O itself did not cause situs inversus but increased the incidence of phenylephrine-induced situs inversus. This additive effect was blocked by prazosin.'] |
['The interruption of hepatic arterial flow when performing a bilioenteric anastomosis has been reported to usually bring about serious postoperative complications, such as anastomotic leakage, hepatic abscess and infarction. We aimed to evaluate the surgical implications of the interlobar hepatic artery when patients with advanced biliary tract carcinomas undergo surgical resection with a bilioenteric anastomosis.', 'In 7 patients with advanced biliary tract carcinomas, the combined resection of the liver (greater than hemihepatectomy in 2 and less than hemihepatectomy in 5), extrahepatic bile duct, hepatic artery (right hepatic artery in 5, right and left hepatic artery in 1, left hepatic artery in 1), and the portal vein was performed in 4 patients. The portal vein was reconstructed in all 4 patients. The hepatic artery was reconstructed in only one patient, with combined resection of both right and left hepatic arteries, but was not reconstructed in 2 other patients, even though they underwent resection greater than hemihepatectomy.', 'The interlobar hepatic artery running into the Glissonian sheath around the hepatic duct confluence could be preserved in 5 patients, as shown by angiography, but could not be preserved in 2 patients who underwent greater than hemihepatectomy. Moderate and transient ischemic liver damage occurred, but no serious postoperative complications were induced in any of the 5 patients in the unilateral hepatic artery preserved group. However, both cases without preservation of the hepatic artery encountered liver failure, liver abscess and leakage of bilioenteric anastomosis, and one patient died of multiple organ failure.'] |
['To determine the gastroprotective and antisecretory effect of ethanol extract from matico leaves (Piper aduncum) in animal models.', 'To evaluate the gastroprotective effect, 220 mice of the Balb C57 strain were used. They were randomized in 22 groups of ten animals each, in which the formation of gastric ulcers was induced with indomethacin. Gastroprotection was determined by evaluating three aspects: inflammation, number of hemorrhagic shocks and number of ulcers. To evaluate the antisecretory effect, 64 white male Holtzman rats were used, which were randomized in eight groups of eight animals, one control and seven groups of treatment with one extract dose level and two phytochemical dose levels. Antisecretion was obtained through the pylorus ligation.', 'Regarding gastroprotection, dichloromethane, chloroform, hexane and methanol extracts decreased inflammation to over 66% (p<0,05). The ethanolic extract shows 100% activity in reducing the number of hemorrhagic bands (p<0,05). The chloroform extract shows antiulcer activity at 75% (p<0,05). In terms of antisecretion, the phytochemical in capsules containing the ethanolic extract achieved 72% reduction of the gastric secretion volume (p<0,01) and 104,3% (p<0,01) PH increase.'] |
['The prevalence of obesity among Mexican women is high and it could be related to micronutrient status. We evaluated in a cross-sectional study the associations of zinc and vitamins A, C and E concentrations with BMI, central adiposity, body fat and leptin concentration.', 'Women aged 37\u2009±\u20097.5\u2009years (n\u2009=\u2009580) from 6 rural communities in Mexico were evaluated. Anthropometric measurements included weight, height, waist and hip circumference. A fasting blood sample was taken for the analysis of glucose, lipid profile, leptin, zinc, and vitamins A, C and E. Body composition was determined by DEXA (Hologic Mod Explorer).', 'The prevalence of overweight and obesity was 36% (BMI\u2009>\u200925 Kg/m2) and 44% (BMI\u2009>\u200930 Kg/m2), respectively. Prevalence of zinc and vitamins C and E deficiencies were similar in obese, overweight and normal weight women. No vitamin A deficiency was found. Vitamin C was negatively associated with BMI, waist-to-height ratio, and leptin concentrations (p\u2009<\u20090.05). Vitamin A was positively associated with leptin (p\u2009<\u20090.05). When stratifying by BMI, % body fat and waist circumference, high leptin concentrations were associated with lower zinc and lower vitamin C concentrations in women with obesity (p\u2009<\u20090.05) and higher vitamin A concentrations in women without obesity (p\u2009<\u20090.01). Vitamin E status was not associated with any markers of obesity.'] |
['Mammography screen-detected breast cancers have a better prognosis than predicted from established prognostic markers. A search for additional features that are characteristic for these tumours and their prognosis is needed to reduce overtreatment, a recognized challenge in breast cancer patient management today. Here, we have investigated the occurrence and importance of tumour elastosis.', 'We performed a population based retrospective study of breast cancers detected in the Norwegian Breast Cancer Screening Programme in Vestfold County during 2004-2009. In total, 197 invasive screen-detected cancers and 75 interval cancers in patients aged 50-69 years were compared with regard to standard clinico-pathological parameters and tumour shape, as well as ER, PR, HER2 and Ki67 expression. In particular, the presence of elastotic material in tumours was graded on a 4-tiered scale (score 0-3).', 'Screen-detected cancers had a significantly higher content of stromal elastosis than interval cancers (p < 0.001). High content of elastosis (score 3) correlated strongly with stellate tumour shape, low histological grade, and ER+/HER2- status. Further, high elastosis score was significantly associated with lower Ki67 expression. In survival analyses, cases with high elastosis demonstrated increased recurrence free (p = 0.03) and disease-specific survival (p = 0.11) compared to cases with low elastosis.'] |
['Bupropion HCl is a widely used antidepressant that is known to cause seizures in a dose-dependent manner. Many patients taking antidepressants will consume alcohol, even when advised not to. Previous studies have not shown any interactions between bupropion HCl and alcohol. However, there have been no previous studies examining possible changes in seizure threshold induced by a combination of alcohol and bupropion HCl.', 'Experimentally naïve female Swiss albino mice (10 per group) received either single doses of bupropion HCl (ranging from 100 mg/kg to 120 mg/kg) or vehicle (0.9% NaCl) by intraperitoneal (IP) injection in a dose volume of 10 ml/kg, and single-dose ethanol alone (2.5 g/kg), or vehicle, 5 min prior to bupropion dosing. The presence or absence of seizures, the number of seizures, the onset, duration and the intensity of seizures were all recorded for 5 h following the administration of ethanol.', 'The results show that administration of IP bupropion HCl alone induced seizures in mice in a dose-dependent manner, with the 120 mg/kg dose having the largest effect. The percentage of convulsing mice were 0%, 20%, 30% and 60% in the 0 (vehicle), 100, 110, and 120 mg/kg dose groups, respectively. Pretreatment with ethanol produced a larger bupropion HCl-induced convulsive effect at all the doses (70% each at 100, 110 and 120 mg/kg) and a 10% effect in the ethanol + vehicle only group. The convulsive dose of bupropion HCl required to induce seizures in 50% of mice (CD50), was 116.72 mg/kg for bupropion HCl alone (CI: 107.95, 126.20) and 89.40 mg/kg for ethanol/bupropion HCl (CI: 64.92, 123.10).'] |
["Asthmatic patients have a higher susceptibility to rhinovirus (RV) infection, and impaired IFN-β and IFN-λ production has been demonstrated in bronchial epithelial cells from asthmatic adults upon exposure to RV. However, the mechanisms underlying the increased susceptibility of asthmatic patients to RV infection remain poorly understood. The present study aimed to elucidate the characteristics of the immune responses of asthmatic patients' peripheral blood mononuclear cells (PBMCs) to RV exposure.", 'PBMCs obtained from 3 different age groups (2-6 years: young-children group; 7-19 years: youth group; ≥20 years: adult group) of asthmatic patients and nonasthmatic control subjects were stimulated with RV-14 for 72 h. Healthy adults with a history of childhood asthma were also enrolled. The concentrations of IFN-α, IL-6, TNF-α, IL-10, and soluble Fas ligand (sFasL) in the culture supernatants were measured by ELISA.', 'When compared with age-matched control subjects, IFN-α production was significantly lower in the asthmatic youth group. IL-6, TNF-α, IL-10, and sFasL productions were significantly lower in both the asthmatic youth group and the adult group. Such impaired responses were not found in healthy adults with a history of childhood asthma. No significantly different responses were found between the asthmatics and controls in the young-children group, whereas young asthmatic children with persistent wheeze during a 2-year follow-up showed significantly lower IL-10 production than those without wheeze.'] |
['Reactive hyperemia (RH) in the forearm circulation is an important marker of cardiovascular health, yet the underlying vasodilator signaling pathways are controversial and thus remain unclear.', 'We hypothesized that RH occurs via activation of inwardly rectifying potassium (KIR) channels and Na(+)/K(+)-ATPase and is largely independent of the combined production of the endothelial autocoids nitric oxide (NO) and prostaglandins in young healthy humans.', 'In 24 (23±1 years) subjects, we performed RH trials by measuring forearm blood flow (FBF; venous occlusion plethysmography) after 5 minutes of arterial occlusion. In protocol 1, we studied 2 groups of 8 subjects and assessed RH in the following conditions. For group 1, we studied control (saline), KIR channel inhibition (BaCl2), combined inhibition of KIR channels and Na(+)/K(+)-ATPase (BaCl2 and ouabain, respectively), and combined inhibition of KIR channels, Na(+)/K(+)-ATPase, NO, and prostaglandins (BaCl2, ouabain, L-NMMA [N(G)-monomethyl-L-arginine] and ketorolac, respectively). Group 2 received ouabain rather than BaCl2 in the second trial. In protocol 2 (n=8), the following 3 RH trials were performed: control; L-NMMA plus ketorolac; and L-NMMA plus ketorolac plus BaCl2 plus ouabain. All infusions were intra-arterial (brachial). Compared with control, BaCl2 significantly reduced peak FBF (-50±6%; P<0.05), whereas ouabain and L-NMMA plus ketorolac did not. Total FBF (area under the curve) was attenuated by BaCl2 (-61±3%) and ouabain (-44±12%) alone, and this effect was enhanced when combined (-87±4%), nearly abolishing RH. L-NMMA plus ketorolac did not impact total RH FBF before or after administration of BaCl2 plus ouabain.'] |
['Oxidative stress induced by free fatty acids contributes to the development of cardiovascular diseases in patients with metabolic syndrome. Reducing oxidative stress may attenuate these pathogenic processes. Activation of AMP-activated protein kinase (AMPK) has been reported to reduce intracellular reactive oxygen species (ROS) levels. The thioredoxin (Trx) system is a major antioxidant system. In this study, we investigated the mechanisms involved in the AMPK-mediated regulation of Trx expression and the reduction of intracellular ROS levels.', 'We observed that activation of AMPK by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) significantly reduced ROS levels induced by palmitic acid in human aortic endothelial cells. Activation of AMPK increased expression of the antioxidant Trx, which mediated the ROS reduction. RT-PCR showed that AMPK regulated Trx at the transcriptional level.', 'Forkhead transcription factor 3 (FOXO3) was identified as the target transcription factor involved in the upregulation of Trx expression. FOXO3 bound to the Trx promoter, recruited the histone acetylase p300 to the Trx promoter, and formed a transcription activator complex, which was enhanced by AICAR treatment. AMPK activated FOXO3 by promoting its nuclear translocation. We further showed that AICAR injection increased the expression of Trx and decreased ROS production in the aortic wall of ApoE-/- mice fed a high-fat diet.'] |
['Shoulder function may be changed after healing of a nonoperatively treated clavicular fracture, especially in cases of clavicular shortening or mal-union. We investigated scapular orientations and functional outcome in healed clavicular fractures with and without clavicular shortening.', '32 participants with a healed nonoperatively treated midshaft clavicular fracture were investigated. Motions of the thorax, arm, and shoulder were recorded by standardized electromagnetic 3D motion tracking. The DASH score and Constant-Murley score were used to evaluate functional outcome. Orientation of the scapula and humerus at rest and during standardized tasks, and strength and function of the affected shoulders were compared with corresponding values for the uninjured contralateral shoulders.', 'Mean clavicular shortening was 25 mm (SD 16). Scapula protraction had increased by mean 4.4° in rest position in the affected shoulders. During abduction, slightly more protraction, slightly more lateral rotation, and slightly less backward tilt was found for the affected shoulders. For anteflexion, the scapular orientations of the affected shoulders also showed slightly increased protraction, slightly increased lateral rotation, and slightly reduced backward tilt. Scapulohumeral kinematics, maximum humerus angles, and strength were not associated with the degree of clavicular shortening. All participants had excellent performance on the Constant-Murley score and DASH score.'] |
['To determine whether serum uric acid: (1) is associated with cardiovascular disease (CVD) death and/or all-cause mortality in type 2 diabetes; and (2) consistent with published data, predicts these outcomes in older patients and those of southern European ethnicity.', 'We studied those 1,268 (98%) of 1,294 type 2 participants in the observational Fremantle Diabetes Study who had a fasting serum uric acid measured at baseline. Mortality data were collected over a mean (+/-SD) 10.3 +/- 3.9 years. Cox proportional hazards modelling was used to determine independent baseline predictors of CVD and all-cause death including fasting serum uric acid as a continuous variable and quartiles.', 'During follow up, 525 deaths occurred (41.4% of the cohort) of which 271 (51.6%) were attributed to CVD. In univariate analyses, patients in the highest uric acid quartile had the greatest CVD and all-cause mortality (p = 0.007 and p = 0.001). After adjustment for significant variables in the most parsimonious model, baseline serum uric acid was not an independent associate of CVD or all-cause mortality whether entered as a continuous variable (HR 1.11 [95% CI 0.96-1.27] and 1.10 [95% CI 0.98-1.22] for a 0.1 mmol/l increase, respectively) or as quartiles (p > 0.10). Analyses of 638 patients >65 years of age and 231 of southern European ethnicity produced similar results.'] |
['The purpose of this study was to determine whether follistatin-free activin A (an inhibin-related protein with rising serum levels before term labor) is associated with spontaneous preterm birth in an outpatient population.', 'From 10 centers, 2929 women were enrolled in the Preterm Prediction Study. Plasma was isolated from blood samples obtained at 24 and 28 weeks of gestation and stored. A nested case-controlled study was performed; there were 197 women with spontaneous preterm birth before 37 weeks of gestation with 24-week samples and 142 cases with 28-week samples that were matched to an equal number of term control samples from each time point. A follistatin-free activin A enzyme-linked immunosorbent assay was performed, with results interpreted as positive or negative (defined as a value less than the assay limit of sensitivity). A comparison of follistatin-free activin A with other tests that were associated with spontaneous preterm birth (alpha-fetoprotein, alkaline phosphatase, cortisol, granulocyte colony-stimulating factor, fetal fibronectin, and cervical interleukin-6) was also performed.', "The odds ratio for associated spontaneous preterm birth at <37 weeks of gestation if the follistatin-free activin A result was positive was 1.16 at 24 weeks (95% CI, 0.62-2.17) and 1.39 at 28 weeks (95% CI, 0.68-2.84). A positive follistatin-free activin A result at either 24 or 28 weeks was not associated with a positive test for any of the other laboratory tests, except granulocyte colony-stimulating factor at 28 weeks' gestation."] |
['Heart failure is an important cause of death in patients with rheumatoid arthritis (RA). Evidence suggests that immune mechanisms contribute to myocardial injury and fibrosis, leading to left ventricular diastolic dysfunction (LVDD). The purpose of this study was to identify a signature of LVDD in patients with RA by analyzing the responsiveness of the innate and adaptive immune systems to stimulation ex vivo.', 'RA patients (n=212) enrolled prospectively in a population-based cohort underwent echocardiography, and LV function was classified as normal, mild LVDD, or moderate-to-severe LVDD. The release of 17 cytokines by blood mononuclear cells in response to stimulation with a panel of 7 stimuli or in media alone was analyzed using multiplex immunoassays. Logistic regression models were used to test for associations between a multicytokine immune response score and LVDD, after adjusting for clinical covariates.', 'An 11-cytokine profile effectively differentiated patients with moderate-to-severe LVDD from those with normal LV function. An immune response score (range 0-100) was strongly associated with moderate-to-severe LVDD (odds ratio per 10 units 1.5 [95% confidence interval 1.2-2.1]) after adjusting for serum interleukin-6 levels, brain natriuretic peptide values, and glucocorticoid use, as well as other RA characteristics and LVDD risk factors.'] |
['To characterize the intraindividual relationships between changes in weight, glycosylated hemoglobin (HbA1c) levels, and reported total daily insulin dose between clinic visits in adolescent boys with type 1 diabetes (T1D).', 'Intraindividual changes in HbA1c, anthropometric data, and reported total daily insulin dose between consecutive visits for 94 adolescent boys with T1D were analyzed.', "Average quarterly weight gain was 2.8 kg during periods of improving, 1.5 kg during periods of minimal change, and 0.8 kg during periods of worsening glycemic control (improving vs. minimal change p < 0.001; minimal change vs. worsening p = 0.11; improving vs. worsening p < 0.001). Analyzing the quarterly weight velocity according to change in reported total daily dose of insulin, we found significantly greater weight gain during intervals when the family reported a decreasing insulin dose compared to intervals when the family reported no change in insulin dose (p = 0.003). Conversely, weight change during periods of reported increasing insulin dose was similar to that when the family reported that the boy's insulin dose did not change."] |
['Chondrocyte death, a notable feature of osteoarthritis, may play a role in the initiation of cartilage degeneration. The present study was aimed at uncovering the nature and involvement of cell death in the initiation of cartilage degeneration induced by mechanical trauma.', 'Articular cartilage discs obtained from healthy skeletally mature horses were subjected to a single-impact load (500 g from 50 mm) using a simple drop-tower device and cultured in vitro for 48 h. Chondrocyte death was examined using two independent methods: transmission electron microscopy and caspase-3 activity assay. To elucidate the signalling mechanisms involved in impact-induced cell death measured by terminal deoxynucleotidyl transferase-deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL), cartilage discs were incubated with specific caspase-3, -8 and -9 inhibitors prior to impact. Additionally, weight gain and glycosaminoglycan (GAG) release, markers of cartilage degeneration were monitored.', 'After 48 h, ultrastructural evidence of apoptosis was observed. Caspase-3 was activated after 12h of culture post-impact. When quantified by TUNEL, impact trauma induced death in 52.6% of superficial chondrocytes after 48 h in culture, compared to 4.2% in unimpacted controls. Specific caspases-3 and -9 inhibitors significantly reduced impact-induced apoptosis to 24.3% and 14.7%, respectively. Caspase-8 inhibition had no effect on chondrocyte death (60.3%). Impact-induced GAG release into the medium was significantly reduced by inhibition of cell death, but weight gain remained unaffected by caspase inhibition.'] |
['To identify the most important epidermal growth factor (EGF) receptor ligand in the LH or hCG signal pathway in human ovary.', 'A retrospective clinical study.', 'Tertiary university hospital.', 'Ninety-eight infertile patients who underwent IVF-embryo transfer.', 'Sera and follicular fluid were collected at the time of oocyte retrieval. The levels of EGF, transforming growth factor-alpha (TGFalpha), and amphiregulin (AR) were measured in follicular fluid and sera by using ELISA.', 'The relationships between the level of AR and level of hCG, fertilization rate, and embryo quality.', 'Amphiregulin was abundantly expressed in follicular fluid after hCG stimulation. Although large differences were found between AR and both EGF and TGFalpha in follicular fluid, no significant difference was detected in the levels of the three EGF receptor ligands in sera. The level of AR was inversely correlated with the fertilization rate and hCG level, whereas little significant association was observed between the level of AR and embryo quality.'] |
['The stage-dependent organization of the cardiomyocytes during formation of the different layers of the developing ventricular wall is critical for the establishment of a functional heart, but the instructive signals involved are still poorly known. We have addressed the potential role of Wnt-11 in the control of early ventricular myocardium assembly.', 'We demonstrate by means of expression analysis and a mouse model in which Wnt-11 function has been inactivated that Wnt-11 is expressed by the embryonic ventricular cardiomyocytes and serves as one important signal for ventricular wall development. In the absence of Wnt-11, the coordinated organization, intercellular contacts, co-localized expression of the cell adhesion components N-cadherin and beta-catenin, and the cytoskeleton of the differentiating ventricular cardiomyocytes are all disturbed. Moreover, the ventricular wall lacking Wnt-11 signalling is thinner and the expression of the Gata-4, Nkx2.5, Mef2c, ANP, and BNP genes is down-regulated relative to controls. These defects lie behind disturbed embryonic cardiac functional development, marked by an increase in the ventricular relaxation time during the early diastole.'] |
['Areca quid chewing, a major risk factor contributing to the occurrence of oral cancer and precancer, has been reported to be associated with the severity and high prevalence of periodontal diseases in areca quid chewers. As dendritic cells are critically involved in the regulation of innate and adaptive immunity in oral mucosa, the objective of the present study was to investigate the effect of areca nut extracts (ANE) on the differentiation and reactivity of dendritic cells derived from monocytes.', 'Human peripheral blood monocytes were cultured in the presence of granulocyte-monocyte colony-stimulating factor and interleukin-4 for 7 d to generate dendritic cells. To examine the effect of ANE on the generation of dendritic cells, the monocytes were exposed to ANE throughout the 7 d culture period. In addition, the effect of ANE on the maturation of monocyte-derived dendritic cells induced by lipopolysaccharide (LPS) was examined.', 'Monocytes cultured in granulocyte-monocyte colony-stimulating factor and interleukin-4 exhibited a typical phenotype of dendritic cells, as evidenced by the heightened expression of human leukocyte antigen (HLA)-DR, CD11c and the co-stimulatory molecules CD40, CD80 and CD86. Exposure of the monocytes to ANE did not influence the expression of HLA-DR and CD11c, but markedly attenuated the proportion of CD40-positive cells and the mean fluorescence intensity of CD86. The expression of co-stimulatory molecules in LPS-activated dendritic cells was not affected, whereas the mRNA expression of interleukin-12 induced by LPS was markedly suppressed by ANE treatment in a concentration-dependent manner.'] |
['Tamoxifen is an effective drug for the treatment and prevention of breast cancer. It is extensively metabolized by the human cytochrome P450 enzyme system into several metabolites. Of these, 4-hydroxy-tamoxifen (4-OH-Tam) is an active metabolite, which has greater anti-estrogenic potency than the parent drug, tamoxifen. We reported recently that 4-hydroxy-N-desmethyl-tamoxifen (endoxifen) could also be active. The progesterone receptor (PR) messenger ribonucleic acid (mRNA) expression is commonly studied as a marker of estrogenic effect in breast cancer cells and PR levels in breast cancer patients are correlated with tamoxifen response. We, therefore, determined the effect of endoxifen and 4-OH-Tam on 17beta-estradiol (E2)-induced PR mRNA expression in an estrogen receptor-positive human breast cancer cell line.', 'MCF-7 cells were treated with drugs for 24 h. The total ribonucleic acid (RNA) was harvested and transcribed into complementary deoxyribonucleic acids (cDNAs). The PR mRNA level was measured by using real-time reverse transcription polymerase chain reaction (RT-PCR). The PR expression data were normalized using a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression. We measured the metabolite concentrations in the cultured media by high performance liquid chromatography (HPLC) to determine whether there was conversion of one metabolite to the other.', 'Consistent with previous reports, the dose-response of the E2 effect on the PR expression indicated an ED(50) value of approximately 60 pM and the maximum induction of PR mRNA was nearly ten-fold. When 10(-10) M E2 was used, induction of the PR expression was observed in 2 h and reached its maximum at 24 h. In this assay, neither endoxifen nor 4-OH-Tam alone produced any change in the PR mRNA expression. However, both endoxifen and 4-OH-Tam decreased the E2-induced PR expression with similar potency. There was very little interconversion between the two metabolites during the culture.'] |
['Malnutrition is frequent in the geriatric population and is often undetected and untreated. Although we often use serum albumin as a nutritional marker, it has limitations in elderly patients in terms of predicting diseases and infections. Anthropometric measurements are not commonly used, despite their simple, easy, and effective characteristics. We evaluated the associations between anthropometric measurements with other nutritional factors and examined its relationship with mortality, decubitus ulcer, length of hospital stay and antibiotic usage.', 'We enrolled 223 patients, performed anthropometric measurements and then followed them for a mean of 24 months.', 'Patients with hypoalbuminemia but with normal body measurements tended to increase serum albumin levels over the next 24 months and had more favorable outcomes including being discharged. Patients with normal albumin but decreased body measurements resulted in a progressive drop in serum albumin and had a higher mortality rate. Additionally, patients with hypoalbuminemia had higher antibiotic usage than patients without hypoalbuminemia. Decreases in anthropometric measurements were related to mortality, length of hospital stay, and decubitus ulcer.'] |
['Atropine is an anticholinergic drug which is commonly used in clinical practice. The effect of parasympathetic block with atropine on dynamic cerebrovascular regulation remains unclear. This study was aimed to identify effects of vagolytic atropine on cerebrovascular response during acute orthostatic hypotension in humans.', 'Continuous middle cerebral blood flow velocity (CBFV, transcranial Doppler) and arterial blood pressure (ABP, Finometer) were measured during a sit-to-stand procedure in 10 healthy subjects with placebo and vagolytic (10 µg/kg) doses of atropine. Cerebral vascular tone was assessed by cerebrovascular resistance (CVR = ABP / CBFV). Dynamic cerebral autoregulation was also assessed by transfer function analysis of ABP and CBFV.', 'During the standing session, ABP fell to a similar extent in both groups by an average of 23 to 25 mmHg (26% to 29%). CBFV also fell in all subjects but significantly more in vagolytic atropine (-15.0 ± 7.0 cm/s) compared with placebo (-12.0 ± 5.8 cm/s, P < 0.05). CVR was decreased significantly in the placebo group during posture change (1.56 ± 0.44 vs. 1.38 ± 0.38, P < 0.05), in contrast, lesser decreased in the atropine group (1.60 ± 0.50 vs. 1.53 ± 0.42, P = 0.193). Transfer function coherence in the very-low-frequency range was significantly increased in the atropine group during the standing session (0.55 ± 0.14), compared with the sitting session (0.45 ± 0.14, P = 0.006).'] |
['The presence of cholesterol in the Human Immunodeficiency Virus (HIV) lipid envelop is important for viral function as cholesterol depleted viral particles show reduced infectivity. However, it is less well established whether other viral membrane lipids are also important for HIV infection. The ABCB4 protein is a phosphatidyl choline (PC) floppase that mediates transport of PC from the inner to the outer membrane leaflet. This property enabled us to modulate the lipid composition of HIV vectors and study the effects on membrane composition and infection efficiency.', 'Virus generated in the presence of ABCB4 was enriched in PC and cholesterol but contained less sphingomyelin (SM). Viral titers were reduced 5.9 fold. These effects were not observed with an inactive ABCB4 mutant. The presence of the ABC transport inhibitor verapamil abolished the effect of ABCB4 expression on viral titers. The ABCB4 mediated reduction in infectivity was caused by changes in the viral particles and not by components co purified with the virus because virus made in the presence of ABCB4 did not inhibit virus made without ABCB4 in a competition assay. Incorporation of the envelope protein was not affected by the expression of ABCB4. The inhibitory effect of ABCB4 was independent of the viral envelope as the effect was observed with two different envelope proteins.'] |
['To test the efficacy of Counselor-Assisted Problem Solving (CAPS) versus an Internet resource comparison (IRC) condition in reducing behavior problems in adolescents following traumatic brain injury (TBI).', 'Randomized clinical trial with interviewers naive to treatment condition.', "Three large tertiary children's hospitals and 2 general hospitals with pediatric commitment.", 'A total of 132 children and adolescents aged 12 to 17 years hospitalized during the previous 6 months for moderate to severe TBI.', 'Participants in CAPS (n = 65) completed 8 to 12 online modules providing training in problem solving, communication skills, and self-regulation and subsequent synchronous videoconferencing with a therapist. Participants in the IRC group (n = 67) received links to Internet resources about pediatric TBI.', 'Child Behavior Checklist administered before and after completion of treatment (ie, approximately 6 months after treatment initiation).', 'Post hoc analysis of covariance, controlling for pretreatment scores, was used to examine group differences in behavior problems in the entire sample and among older (n = 59) and younger adolescents (n = 53). Among older but not younger adolescents, CAPS resulted in greater improvements on multiple dimensions of externalizing behavior problems than IRC.'] |
['To investigate the value of serum globulin levels before treatment in predicting the prognosis of patients with nasopharyngeal carcinoma (NPC).', 'A total of 127 patients with non-disseminated NPC were recruited between January, 2009 and December, 2013 at Nanfang Hospital. The pretreatment serum globulin levels were analyzed with the receiver-operating characteristic (ROC) curve analysis to select the cut-off point for low and high pretreatment serum globulin levels. Kaplan-Meier and multivariable analyses were used to evaluate the predictive value of serum globulin levels.', 'The ROC curve analysis determined 30.05 g/L as the optimal cut-off value for pretreatment serum globulin level, which was significantly associated with gender (P=0.024) and N stage (P=0.016). Kaplan-Meier analysis showed that a high pretreatment serum globulin level (>30.05 g/L) significantly predicted poor progression-free survival (P=0.019), overall survival (P=0.034) and distant metastasis-free survival (P=0.049); multivariate analysis identified pretreatment serum globulin level as an independent prognostic factor for progression-free survival (HR=2.344, P=0.031).'] |
['Fewer intraperitoneal adhesions have been observed after laparoscopic surgery compared with conventional techniques. The aim of this study is to assess the effect of the pneumoperitoneum on mesothelial cell fibrinolytic activity by use of an in vitro model.', 'Human peritoneal mesothelial cells were seeded onto 24-well plates and incubated in carbon dioxide or helium at 5 mm Hg for 4 hours or standard culture conditions. Supernatant was removed for analysis at 0, 24, 48, and 72 hours after gas incubation and analyzed for plasminogen activator activity, total tissue plasminogen activator (tPA), and total plasminogen activator inhibitor-1 (PAI-1) concentrations by use of an enzyme-linked immunosorbent assay. The effect of different insufflation pressures (0, 7, and 14 mm Hg) was also examined.', 'Enhanced plasminogen activator activity was observed at 48 hours and 72 hours from cells exposed to CO(2) (P<.04 each) and helium (P<.05 each) compared with control. This was associated with a decrease in PAI-1 concentrations at 48 and 72 hours in both the CO(2) and helium groups compared with control (P<.03 each, CO(2) vs control; and P<.04 each, helium vs control). No changes in tPA levels were observed. Changes in insufflation pressures did not affect plasminogen activator activity.'] |
['Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis, the formation of which is triggered by hypoxia, cytokines, and growth factors and is also induced by activation of the adenosine 2B receptor. VEGF is neuroprotective in several models of experimental brain injury and is increased in brain after traumatic brain injury (TBI) in humans and experimental animals. Adenosine is a neuroprotective purine metabolite that increases in cerebrospinal fluid (CSF) after clinical TBI in children. We hypothesized that VEGF levels would 1). be increased in CSF after TBI in infants and children, and 2). be preceded by increases in CSF adenosine. To test this hypothesis, we designed a case-control study to compare the CSF of infants and children after severe TBI with that of uninjured children.', 'Using an Institutional Review Board-approved protocol, we compared CSF concentrations of VEGF (by enzyme-linked immunosorbent assay) and adenosine (by high-performance liquid chromatography) in 73 samples from 14 infants and children with severe TBI (Glasgow Coma Scale score <or=8) with those in CSF from 5 noninjured control subjects. Patients received standard neurointensive care.', 'Mean VEGF levels were increased after TBI versus control (39.8 +/- 6.2 versus 14.9 +/- 1.5 ng/dl, mean +/- standard error of the mean, P = 0.0002) and peaked at 91.6 +/- 26.4 ng/dl, approximately 6 times control (P = 0.001). Peak VEGF occurred at 22.4 hours after injury. There was a trend toward increased adenosine concentration after TBI versus control (18.3 +/- 3.5 versus 11.5 +/- 2.3 nmol/L), but this did not reach statistical significance. A multivariate regression model showed an independent, significant association between the concentrations of VEGF and adenosine.'] |
['Elevated plasma leptin levels have been demonstrated in obesity and hypertension. These conditions are documented as insulin-resistant states with sympathetic overactivity. However, the relation between plasma insulin, leptin levels, and sympathetic nerve activity, especially after meals, has not been established.', 'To evaluate the impact of insulin sensitivity and obesity on the response of plasma leptin to acute physiologic insulin elevation, we studied 31 nonobese (body mass index [BMI] < 25 kg/m(2)) and 38 overweight or obese (obese; BMI >/= 25 kg/m(2)) normotensive men. Using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), the subjects were subdivided into insulin-sensitive (HOMA-IR <2.5) and insulin-resistant (HOMA-IR >/=2.5) groups. There were 11 nonobese and 28 obese men who were insulin-resistant. Blood pressure (BP), plasma glucose, insulin, leptin, and norepinephrine (NE) levels were measured before and after 75-g oral glucose loading every 30 min for 120 min.', 'In nonobese subjects, fasting plasma insulin and leptin levels and areas-under-the-curves (AUC) for insulin and leptin were significantly lower in the insulin-sensitive group than in the insulin-resistant group. In the insulin-sensitive group regardless of BMI, plasma leptin levels decreased after glucose loading. Plasma glucose, insulin, NE, and BP levels increased in nonobese insulin-sensitive subjects after glucose loading, whereas in obese insulin-sensitive subjects, plasma NE and BP did not change in response to glucose. In insulin-resistant subjects regardless of BMI, marked elevations in plasma insulin did not cause any change in plasma leptin, NE, and BP levels.'] |
['Upregulation of syndecan-1, a member of the transmembranous proteoglycans that serves as a coreceptor for a wide pool of extracellular ligands, has been well documented in enabling the promotion of growth and invasion of endometrial cancer. As a step toward understanding a potential role for syndecan-1 in this process, we questioned whether syndecan-1 upregulates tumor-promoting characteristics, particularly, angiogenesis in an in vivo human xenograft tumor model.', 'Human syndecan-1 was stably transfected into human endometrial adenocarcinoma 1A cells, and resulting transfectants were subcutaneously grafted into athymic mice; their outcomes were examined with respect to the enhancement of tumor growth and angiogenesis by immunohistochemistry, immunoblotting, and zymography.', 'Overexpression of syndecan-1 promoted tumor growth concomitant with increased angiogenesis in tumor xenografts as evidenced by an increase in immunoreactivity for vascular endothelial growth factor and vascular endothelial cell marker CD34. Furthermore, zymographic studies revealed that syndecan-1 overexpression markedly enhanced activities of matrix metalloproteinases 2 and 9.'] |
['Tuberculosis (TB) represents a major global health problem. The prognosis of clinically active tuberculosis depends on the complex interactions between Mycobacterium tuberculosis (Mtb) and its host. In recent years, autophagy receives particular attention for its role in host defense against intracellular pathogens, including Mtb. In present study, we aim to investigate the relationship of autophagy induction by clinical isolates of Mtb with the clinical outcomes in patients with TB.', 'We collected 185 clinical isolates of Mtb, and determined the effect of these Mtb isolates on autophagy induction in macrophages. It was found that most of clinical isolates of Mtb were able to induce autophagosome formation in macrophages, however, the autophagy-inducing ability varied significantly among different isolates. Of importance, our results revealed that patients infected by Mtb with poor autophagy-inducing ability displayed more severe radiographic extent of disease (p<0.001), and were more likely to have unfavorable treatment outcomes (p<0.001). No significant association was observed between the extent of Mtb-induced autophagy with some socio-demographic characteristics (such as gender, age and tobacco consumption), and some laboratory tests (such as hemoglobin, leukocyte count and erythrocyte sedimentation rate). Furthermore, results from logistic regression analysis demonstrated that the defect in autophagy induction by clinical isolates of Mtb was an independent risk factor for far-advanced radiographic disease (aOR 4.710 [1.93-11.50]) and unfavorable treatment outcomes (aOR 8.309 [2.22-28.97]) in TB.'] |
['The periurethral glands are known to produce prostate specific antigen (PSA). With ultra-sensitive assays now routinely available, it is necessary to determine if the periurethral glands significantly influence serum PSA concentration after radical prostatectomy.', 'Serum PSA levels of 46 men, 51 to 89 years old (median age 67) who underwent radical cystoprostatectomy and total urethrectomy, were compared with those of 92 men 46 to 91 years old (median age 67) who underwent radical cystoprostatectomy only. All men had transitional cell carcinoma of the bladder without gross or microscopic evidence of prostate cancer and all underwent ileal conduit diversion. Serum was obtained at least 1 year postoperatively. Each specimen was analyzed using the Tosoh, Immulite, and Yu and Diamandis ultra-sensitive PSA assays with analytical detection limits of 0.02 ng./ml., 0.004 ng./ ml. and 0.002 ng./ml., respectively.', 'Median PSA for the radical cystoprostatectomy with urethrectomy group was 0.00 ng./ml. (range 0.00 to 0.14) for each of the 3 assays. For the radical cystoprostatectomy only group the median Tosoh and Immulite PSA assay levels were 0.01 ng./ml. (range 0.00 to 0.22), and median Yu and Diamandis PSA assay level was 0.00 ng./ml. (range 0.00 to 0.31).'] |
['Epithelial junctions between tumor cells inhibit the penetration of anticancer drugs into tumors. We previously reported on recombinant adenovirus serotype 3-derived protein (JO-1), which triggers transient opening of intercellular junctions in epithelial tumors through binding to desmoglein 2 (DSG2), and enhances the antitumor effects of several therapeutic monoclonal antibodies. The goal of this study was to evaluate whether JO-1 cotherapy can also improve the efficacy of chemotherapeutic drugs.', 'The effect of intravenous application of JO-1 in combination with several chemotherapy drugs, including paclitaxel/Taxol, nanoparticle albumin-bound paclitaxel/Abraxane, liposomal doxorubicin/Doxil, and irinotecan/Camptosar, was tested in xenograft models for breast, colon, ovarian, gastric and lung cancer. Because JO-1 does not bind to mouse cells, for safety studies with JO-1, we also used human DSG2 (hDSG2) transgenic mice with tumors that overexpressed hDSG2.', 'JO-1 increased the efficacy of chemotherapeutic drugs, and in several models overcame drug resistance. JO-1 treatment also allowed for the reduction of drug doses required to achieve antitumor effects. Importantly, JO-1 coadmininstration protected normal tissues, including bone marrow and intestinal epithelium, against toxic effects that are normally associated with chemotherapeutic agents. Using the hDSG2-transgenic mouse model, we showed that JO-1 predominantly accumulates in tumors. Except for a mild, transient diarrhea, intravenous injection of JO-1 (2 mg/kg) had no critical side effects on other tissues or hematologic parameters in hDSG2-transgenic mice.'] |
['To assess the relationship between plasma nevirapine concentrations and plasma HIV-1 RNA response in HIV-1-infected patients.', 'An observational cohort analysis.', 'Plasma samples were obtained on a routine basis from 189 patients receiving nevirapine 200mg twice daily, and plasma nevirapine concentrations were measured with reversed phase high performance liquid chromatography. Patients were divided into two groups based on plasma nevirapine concentrations below (and equal to) or above 3 mg/L. The association between steady-state nevirapine concentrations and plasma HIV-1 RNA was determined by multivariate analysis.', 'Out of 189 patients, 13 (7%) had low nevirapine plasma concentrations and 176 patients had concentrations above 3 mg/L. In total, 22 (12%) patients showed virological failure and 8 patients (4%) discontinued nevirapine because of adverse effects. The risk of failure in patients with nevirapine plasma concentrations </=3mg/L was increased (relative risk 5.0, 95% CI 1.8-13.7). Rashes and liver enzyme elevations each occurred in 8% of patients.'] |
['Myocardial fibrosis contributes to cardiac remodeling and loss of cardiac function in myocardial infarction and heart failure. This study used in\xa0vitro and in\xa0vivo models to examine the effects of ursolic acid (UA) on myocardial fibrosis and to explore its potential mechanism.', "Transverse aortic constriction (TAC) surgery was performed in mice to induce cardiac hypertrophy and fibrosis. UA was orally administered 1\xa0week prior to TAC. Two weeks after TAC, myocardial pathology was detected using Masson's trichrome staining and transmission electron microscopy, and heart-to-body weight ratio was measured. For in\xa0vitro studies, cultured cardiac fibroblasts were treated with serum in the presence or absence of UA. The relative levels of miR-21 and p-ERK/ERK, collagen content and cell viability were measured.", 'Ursolic acid attenuated pathological cardiac hypertrophy and myocardial fibrosis in\xa0vivo induced by TAC. Downregulation of miR-21 and p-ERK/ERK were observed in myocardial fibroblasts treated with UA in a dose-dependent manner compared with the control group both in\xa0vitro and in\xa0vivo.'] |
['Endothelial dysfunction is a major underlying mechanism for the elevated cardiovascular risk associated with increased body weight. We aimed to assess the impact of weight loss induced by an intensive very-low-calorie diet (VLCD) on arterial wall function in severely obese patients (SOP).', 'Thirty-four SOP were admitted to the metabolic ward of the hospital for a 3-week period. A VLCD characterized by a liquid diet providing 800 kcal/day was administered. The small artery reactivity to postischemic hyperemia index (saRHI), a surrogate marker of endothelial function, was assessed before and 1 week after hospital discharge. Anthropometry and biochemical parameters were also measured. Obese and non-obese age- and gender-matched groups were recruited for baseline comparisons.', 'SOP had significantly lower saRHI compared with obese and non-obese individuals. SaRHI significantly increased after the intervention in SOP (1.595 ± 0.236 vs. 1.737 ± 0.417, p = 0.015). A significant improvement in glucose (p = 0.026), systolic blood pressure (p = 0.049), LDLc (p < 0.001), and inflammatory parameters was observed. Body weight loss was associated with a higher saRHI (r = -0.385, p = 0.033), and it was the main determinant of saRHI variation independently of confounders (β -0.049, IC 95 % -0.091-0.008, p = 0.021).'] |
['Chronic obstructive pulmonary disease (COPD) can lead to severe disability as the disease advances. The 6-minute walk test (6MWT) is commonly used to measure functional capacity in COPD patients and has three potential outcomes; walking distance, oxygen desaturation, and self-perceived dyspnea assessed by the Borg scale, all reflecting different aspects of COPD. The aim of this study was to identify predictors of all 3 outcomes of 6MWT in patients with COPD.', '370 COPD patients, aged 40-75 yrs, were included from the first phase of the Bergen COPD cohort study. They were examined with spirometry, bioelectrical impedance measurements, 6MWT, Center for Epidemiologic Studies of Depression (CES-D) Scale, Medical Research Council (MRC) dyspnea scale, Charlson index for co-morbidities, self-reported physical activity questionnaire, plasma levels of C-reactive protein (CRP) and arterial blood gases.', 'Significant predictors in the multivariate analyses were sex, age, FEV(1) in % predicted, symptoms of dyspnea (MRC), co-morbidities (Charlson Index) and self-reported physical activity for walking distance, FEV(1) in % predicted and PaO(2) for oxygen desaturation, and body composition, smoking and co-morbidities for self-perceived dyspnea assessed by the Borg scale.'] |
['To evaluate the effect of hypoxia-inducible factor-1alpha (HIF-1alpha) over-expression on the invasion-associated proteins in human prostate cancer cells, as HIF-1alpha is a transcriptional factor that could activate genes involved in the response to hypoxia, but might also enhance the invasive potency of prostate cancer cells.', 'Prostate cancer (LNCaP) cells were transfected with recombinant plasmid pcDNA3.1(-)/HIF-1alpha and pcDNA3.1(-) control vector using a commercial system, designated as LNCaP/HIF-1alpha and LNCaP/pcDNA3.1, respectively. The positive clones were selected with G418 and confirmed by Western blot and indirect immunofluorescence labelling. A polycarbonate filter, coated with a matrix gel, was used to analyse the invasive potency. The expression of E-cadherin, vimentin, cathepsin D, matrix metalloproteinase (MMP2) and urokinase plasminogen activator receptor (uPAR) was detected by Western blot.', 'The expression level of HIF-1alpha in LNCaP/HIF-1alpha was distinctly higher than that in LNCaP/pcDNA3.1 and LNCaP. Many more cells of LNCaP/HIF-1alpha penetrated through the polycarbonate filter than those of LNCaP/pcDNA3.1 and LNCaP. Compared with the LNCaP/pcDNA3.1 and LNCaP cells, the expression of vimentin, cathepsin D, MMP-2 and uPAR were up-regulated in LNCaP/HIF-1alpha, whereas the expression of E-cadherin was down-regulated.'] |
['To test whether GnRH agonist could alter in vivo human immune cells and whether the alteration is related to the success of pregnancy in an in vitro fertilization-embryo transfer (IVF-ET) program.', 'Thirty-six infertile patients were enrolled under the long protocol of GnRH agonist (buserelin acetate) and superovulation with gonadotropin from our IVF-ET program. Peripheral B cells, NK cells, CD4+ and CD8+ T cells, and the expression of CD69, CD25, HLA-DR, and CD71 antigens on the T cells were serially examined by dual-color flow cytometry.', 'B cells, NK cells, CD8+ T cells, and CD71+ T lymphocyte subpopulations were not changed throughout the whole course of treatment. CD4+ T cell and CD25+ T cell subpopulations were significantly down-regulated when the GnRH agonist was used for approximately 2 wk. CD3+CD69+, CD3+CD25+, and CD3+DR+ lymphocyte subpopulations were increased at 7 days (during implantation) and at 14 days after embryo transfer in pregnant patients, but not in patients who failed to get pregnant.'] |
['Platelet inhibition is thought to increase perioperative blood loss in patients with planned coronary artery bypass grafting (CABG). This retrospective study reviews the results of over 10 000 patients with CABG, comparing continued platelet inhibition with preoperative disruption of this therapy.', 'From 1995 to 2007, 12 023 patients underwent isolated CABG and were included in this study. The data were evaluated with regard to preoperative aspirin therapy, EuroScore relevant risk factors, and the operative results. Parameters of the operative outcome were in-hospital mortality, perioperative infarctions, reexploration rate, strokes, pericardial tamponade, blood transfusions, and perioperative drainage loss.', 'The patients were divided into two groups: group A (continuous aspirin therapy till surgery [n = 2519]), and group B (patients with preoperative interruption of their aspirin therapy for at least five days [n = 9504]). There was no difference between the groups with regard to age, EuroScore (4.3 +/- 2.8 vs. 4.2 +/- 2.9), emergency cases (8.8 % vs. 8.7 %), left main stenoses (17.9 % vs. 17.6 %), duration of surgery (198 +/- 53 vs. 198 +/- 52 min.) and sex distribution. The postoperative drainage loss did not differ between groups A and B (834 +/- 781 ml vs. 902 +/- 811 ml), nor did the number of postoperatively administered red cell packages (0.88 +/- 2.7 vs. 1.01 +/- 2.9). When analyzing the three subgroups "on-pump primary CABG", "OPCAB procedures", and "redo CABG", again no difference was found in the main outcome parameters. Only the redo CABG of group B had a higher reexploration rate compared to group A (5 % vs. 3.3 %, P < 0.05).'] |
['Myocellular creatine (Cr) uptake is predominantly governed by the creatine transporter (CreaT) and plays a pivotal role in skeletal muscle energy metabolism. The CreaT belongs to a neurotransmitter transporter family that is functionally regulated by protein tyrosine kinase induced tyrosine phosphorylation. Recently, complement regulatory protein CD59 has been found not only to protect host tissue from C5b-9 complex attack that occurs in sepsis but also to initiate the activation of Src family kinase and tyrosine phosphorylation of its downstream proteins. The purpose of this study was to determine the association between myocellular free Cr, c-Src related tyrosine phosphorylation of the CreaT, and CD59 during sepsis.', 'Male Sprague-Dawley rats (250 to 300 g) were randomized to undergo cecal ligation and puncture (CLP) or sham operation. Fast-twitch gastrocnemius muscles were harvested 24 hours after operation. Myocellular free Cr levels were measured by high-performance liquid chromatography. Combination of protein immunoprecipitation with Western blotting was used to assess tyrosine phosphorylation status of the CreaT and the association between CD59, c-Src, and CreaT.', 'Myocellular free Cr levels were 70% greater after CLP. Tyrosine phosphorylation of the CreaT was significantly increased after CLP as compared to sham operation. Tyrosine phosphorylated c-Src (Tyr-416) in the CreaT-c-Src immune complex was 24% higher after CLP. Sepsis also increased protein expression of tyrosine phosphorylated c-Src (Tyr-416) or CreaT in the CD59-c-Src or CD59-CreaT complex by 20% or 30%, respectively.'] |
['Operative mortality is comparatively higher for coronary artery bypass grafting (CABG) or valve reoperations. Studies of reoperative risk have focussed on surgical techniques. We sought to determine the risk and predictors of poor outcome in current practice, and the influence of preoperative symptoms.', 'For every redo patient (n=289), we selected the best-matched pair of patients who underwent a primary operation (n=578) between 1998 and 2006. Matching variables were age, gender, left ventricular ejection fraction (LVEF) and type of operation. Poor outcome was defined as operative mortality or major morbidity.', 'Median age was 68 (interquartile range 62-73) years and 28% were female for both groups. Severe symptoms and cardiac morbidity dominated the presentation of redo patients. CABG (53%), valve repair/replacement (34%) and combined CABG and valve (12%) were performed with overall operative mortality of 6.6% (median additive EuroScore 7.0) for redo versus 1.6% (median additive EuroScore 4.0) for primary groups (p<.0001). Whereas no significant difference was observed between primary (1.6%) and redo CABG (3.9%, p=.19), valve reoperations had higher operative mortality (9.6% vs 1.5%, p<.0001). Major complications occurred more frequently after redo valve compared to primary valve operations (28% vs 14%, p=.001). Reoperation (odds ratio [OR] 1.26, 95% confidence interval [CI] 0.66-2.42, p=.48) was not a predictor of major adverse event after CABG or valve surgery. Determinants of poor outcome after valve reoperations were New York Heart Association class III/IV (OR 6.86, 95% CI 2.29-12.11, p=.03), duration of extracorporeal circulation (OR 1.17, 95% CI 1.02-1.35, p=.03) and mitral valve replacement (OR 4.07, 95% CI 1.83-36.01, p=.04). The predictors of major adverse events after redo CABG were congestive heart failure (OR 1.85, 95% CI 1.04-8.98, p=.006) chronic obstructive pulmonary disease (OR 17.5, 95% CI 1.87-35.21, p=.05) and interval from prior surgery (OR 1.37, 95% CI 1.09-1.92, p=.01).'] |
['In patients with quiescent asthma, macrophages are the most prevalent cells recovered by bronchoalveolar lavage (BAL). Through activation via their FcepsilonRII receptors or by acting as antigen-presenting cells, macrophages could, in theory, promote the late airway response to allergen.', 'In order to investigate the importance of macrophages and other airway luminal cells in inducing the late airway response, a novel washout experiment was designed.', 'Five patients with ragweed-allergic asthma underwent bronchoscopy and segmental bronchial challenge with either normal saline or short ragweed extract in two segments of one lung. In a third segment of the opposite lung, 12 successive BALs (25 mL each) were performed, followed by challenge with an identical dose of short ragweed (washed-challenged segment). After 24 h, all three challenged segments underwent BAL.', 'Initially, in the washed-challenged segment, over 80% (mean 80.4%, range 68-88%) of the recoverable airway dwelling cells were removed. Unexpectedly, 24 h later these same washed-challenged segments contained more eosinophils in the BAL than the challenged segments from the opposite lung (P = 0.033).'] |
['Anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment in the mouse ovary. We hypothesize that in women AMH signaling also regulates the usage of the primordial follicle pool and hence influences the onset of menopause. Since age at menopause has a strong genetic component, we investigated the role of AMH signaling using a candidate gene approach.', 'In two large population-based cohorts of Dutch post-menopausal women (n = 2381 and n = 248), we examined the association between two polymorphisms, one in the AMH gene and one in the AMH type II receptor (AMHR2) gene, and natural age at menopause.', 'The AMH Ile(49)Ser polymorphism (rs10407022) was not associated with age at menopause in either cohort. In the Rotterdam cohort, the AMHR2 -482 A > G polymorphism (rs2002555) was associated with age at menopause in interaction with the number of offspring (P = 0.001). Nulliparous women homozygous for the G-allele entered menopause 2.6 years earlier compared with nulliparous women homozygous for the A-allele (P = 0.005). In the LASA cohort, women with the G/G genotype tended to enter menopause 2.8 years earlier compared with the A/A genotype (P = 0.063).'] |
['To investigate the mechanism of propranolol on regression of infantile hemangiomas.', 'Propranolol has been found to be effective in treatment of severe hemangiomas of infancy. However, its mechanism of action is as yet unknown.', 'Cultured proliferating and involuting hemangioma endothelial cells were treated with varying concentrations of propranolol for up to 4 days. Analysis was performed using cell viability, migration, and tubulogenesis assays, as well as quantitative RT-PCR and flow cytometry. Western blots and ELISA assays were used to assess protein expression.', 'Treatment with propranolol led to a dose dependent cytotoxic effect in hemangioma endothelial cells with decreased cell viability, migration, and tubulogenesis. This cytotoxic effect was VEGF (vascular endothelial growth factor) dependent, as demonstrated by decreased VEGF, VEGF-R1, and VEGF-R2 production. Decreased signaling through the VEGF pathway resulted in downregulation of PI3/Akt and p38/MAPK activity. Decreased VEGF activity was mediated through the hypoxia inducible factor (HIF)-1α pathway but not through NF-κβ signaling.'] |
['To investigate whether an inflammatory response occurs in patients undergoing infrarenal aortic abdominal aneurysm repair, the localization and timing (ischemia and/or reperfusion) of this activation, and finally whether it affects postoperative pulmonary function.', 'Prospective, observational study.', 'Academic referral center in Italy.', 'We included 12 patients undergoing infrarenal aortic abdominal aneurysm repair and 12 patients undergoing major abdominal surgery.', 'Timed measurement of gene activation (angiotensinogen, angiotensin type 1 receptor, angiotensin-converting enzyme, and interleukin-6 genes) in muscle biopsies by reverse transcriptase-polymerase chain reaction (RT-PCR), and prospective assessment of interleukin-6 plasma concentration and pulmonary function (Pao2/FIO2 and Pao2/PAO2 ratios).', 'After 30 mins of aortic clamping, angiotensinogen, angiotensin type 1 receptor, angiotensin-converting enzyme, and interleukin-6 genes were all overexpressed at RT-PCR studies in quadriceps muscle of patients undergoing aortic abdominal aneurysm repair, and the overexpression persisted after reperfusion. In situ hybridization and immunohistochemistry revealed that the inflammatory response was localized in endothelial cells. A significant increase in plasma interleukin-6 concentrations was then detectable at 6 and 12 hrs after reperfusion in aortic abdominal aneurysm surgery compared with patients undergoing abdominal surgery (p < .05). The increase in interleukin-6 plasma concentration was then followed (12 and 24 hrs after surgery) by a significant reduction of Pao2/ FIO2 and Pao2/PAO2 ratios (p < .05 vs. abdominal surgery).'] |
['Autophagy is activated in ischemic heart diseases, but its dynamics and functional roles remain unclear and controversial. In this study, we investigated the dynamics and role of autophagy and the mechanism(s), if any, during postinfarction cardiac remodeling.', 'Acute myocardial infarction (AMI) was induced by ligating left anterior descending (LAD) coronary artery. Autophagy was found to be induced sharply 12-24 hours after surgery by testing LC3 modification and Electron microscopy. P62 degradation in the infarct border zone was increased from day 0.5 to day 3, and however, decreased from day 5 until day 21 after LAD ligation. These results indicated that autophagy was induced in the acute phase of AMI, and however, impaired in the latter phase of AMI. To investigate the significance of the impaired autophagy in the latter phase of AMI, we treated the mice with Rapamycin (an autophagy enhancer, 2.0 mg/kg/day) or 3-methyladenine (3MA, an autophagy inhibitor, 15 mg/kg/day) one day after LAD ligation until the end of experiment. The results showed that Rapamycin attenuated, while 3MA exacerbated, postinfarction cardiac remodeling and dysfunction respectively. In addition, Rapamycin protected the H9C2 cells against oxygen glucose deprivation in vitro. Specifically, we found that Rapamycin attenuated NFκB activation after LAD ligation. And the inflammatory response in the acute stage of AMI was significantly restrained with Rapamycin treatment. In vitro, inhibition of NFκB restored autophagy in a negative reflex.'] |
['The impact of Society of Thoracic Surgeons predicted mortality risk score on resource use has not been previously studied. We hypothesize that increasing Society of Thoracic Surgeons risk scores in patients undergoing aortic valve replacement are associated with greater hospital charges.', "Clinical and financial data for patients undergoing aortic valve replacement at The Johns Hopkins Hospital over a 10-year period (January 2000 to December 2009) were reviewed. The current Society of Thoracic Surgeons formula (v2.61) for in-hospital mortality was used for all patients. After stratification into risk quartiles, index admission hospital charges were compared across risk strata with rank-sum and Kruskal-Wallis tests. Linear regression and Spearman's coefficient assessed correlation and goodness of fit. Multivariable analysis assessed relative contributions of individual variables on overall charges.", "A total of 553 patients underwent aortic valve replacement during the study period. Average predicted mortality was 2.9% (±3.4) and actual mortality was 3.4% for aortic valve replacement. Median charges were greater in the upper quartile of patients undergoing aortic valve replacement (quartiles 1-3, $39,949 [interquartile range, 32,708-51,323] vs quartile 4, $62,301 [interquartile range, 45,952-97,103], P < .01]. On univariate linear regression, there was a positive correlation between Society of Thoracic Surgeons risk score and log-transformed charges (coefficient, 0.06; 95% confidence interval, 0.05-0.07; P < .01). Spearman's correlation R-value was 0.51. This positive correlation persisted in risk-adjusted multivariable linear regression. Each 1% increase in Society of Thoracic Surgeons risk score was associated with an added $3000 in hospital charges."] |
['To determine the efficiency of our vitrification technique when applied in young fertile women.', 'Clinical research and application.', 'In vitro fertilization center.', 'Twenty-one women were recruited from the navy community with 19 patients finishing the study.', 'Vitrified oocytes with use of the electron microscopic grid method were warmed 6 months after vitrification. Surviving metaphase II oocytes were microinjected for fertilization, and clinical results were evaluated.', 'Survival, fertilization, and cleavage rate. Pregnancy and implantation rate.', 'Three hundred ninety-five oocytes were warmed, of which 320 oocytes (81.0%) survived. Two hundred eighty-five metaphase II oocytes were microinjected for fertilization; 206 of them (72.3%) fertilized, and 53 embryos were transferred to 19 patients (in 20 warming cycles). Twenty-four of 53 transferred embryos (45.3%) implanted as confirmed by ultrasound examination. Of the 20 transfers, 16 resulted in clinical pregnancy (80%), 3 miscarried (15%), and 13 (65%) went on to produce 20 live births, respectively. This is much higher in comparison with our previous data using supernumerary oocytes where the rates of implantation and pregnancy were 6% and 21%. Live-birth rates per warmed oocyte and per injected oocyte were 5.1% and 7.2%, respectively.'] |
["Patients suffering from post-polio syndrome still contribute significantly to the number of patients with chronic respiratory failure requiring home mechanical ventilation (HMV). Many of these patients are treated either with invasive (tracheostomy) or non-invasive (nasal mask) controlled mechanical ventilation i.e. volume-controlled ventilation (VCV). In this group of patients, we have previously shown that bi-level pressure support ventilation (bi-level PSV) decreases the oxygen cost of breathing. The aim of this study was to compare the effect of bi-level PSV, with special regard to the adequacy of ventilation and the oxygen cost of breathing, during the patients' ordinary VCV and spontaneous breathing.", 'Eight post-polio patients on nocturnal VCV were investigated. Five of them were tracheostomized and three of them used a nasal mask. Work of breathing was analysed by assessing differences in oxygen consumption (VO2) using indirect calorimetry. Blood gases were obtained regularly to assess adequacy of ventilation.', 'Bi-level PSV decreases the oxygen cost of breathing in post-polio patients with respiratory failure without decreasing ventilation efficiency. Furthermore, PaCO2 decreased significantly using this mode of ventilation (P < 0.05).'] |
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