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['Developmental language disorder is a heterogeneous diagnostic category. Little research has compared the long-term outcomes of children with different subtypes of language impairment.', 'To determine whether the pattern of language impairment in childhood related to language and literacy outcomes in adulthood.', 'Adults who took part in previous studies as children were traced. There were four groups of participants, each with a different childhood diagnosis: specific language impairment (SLI; n = 19, mean age at follow-up = 24;8), pragmatic language impairment (PLI; n = 7, mean age at follow-up = 22;3), autism spectrum disorder (ASD; n = 11; mean age at follow-up = 21;9), and no childhood diagnosis (typical; n = 12; mean age at follow-up = 21;6). Participants were administered a battery of language and literacy tests.', 'Adults with a history of SLI had persisting language impairment as well as considerable literacy difficulties. Pragmatic deficits also appeared to develop over time in these individuals. The PLI group had enduring difficulties with language use, but presented with relatively intact language and literacy skills. Although there were some similarities in the language profile of the PLI and ASD groups, the ASD group was found to have more severe pragmatic deficits and parent-reported linguistic difficulties in conversational speech.'] |
["Epratuzumab, a humanized anti-CD22 monoclonal antibody, is under investigation as a therapeutic antibody in non-Hodgkin's lymphoma and systemic lupus erythematosus (SLE), but its mechanism of action on B-cells remains elusive. Treatment of SLE patients with epratuzumab leads to a reduction of circulating CD27(negative) B-cells, although epratuzumab is weakly cytotoxic to B-cells in vitro. Therefore, potential effects of epratuzumab on adhesion molecule expression and the migration of B-cells have been evaluated.", 'Epratuzumab binding specificity and the surface expression of adhesion molecules (CD62L, β7 integrin and β1 integrin) after culture with epratuzumab was studied on B-cell subsets of SLE patients by flow cytometry. In addition, in vitro transwell migration assays were performed to analyze the effects of epratuzumab on migration towards different chemokines such as CXCL12, CXCL13 or to CXCR3 ligands, and to assess the functional consequences of altered adhesion molecule expression.', 'Epratuzumab binding was considerably higher on B-cells relative to other cell types assessed. No binding of epratuzumab was observed on T-cells, while weak non-specific binding of epratuzumab on monocytes was noted. On B-cells, binding of epratuzumab was particularly enhanced on CD27(negative) B-cells compared to CD27(positive) B-cells, primarily related to a higher expression of CD22 on CD27(negative) B-cells. Moreover, epratuzumab binding led to a decrease in the cell surface expression of CD62L and β7 integrin, while the expression of β1 integrin was enhanced. The effects on the pattern of adhesion molecule expression observed with epratuzumab were principally confined to a fraction of the CD27(negative) B-cell subpopulation and were associated with enhanced spontaneous migration of B-cells. Furthermore, epratuzumab also enhanced the migration of CD27(negative) B-cells towards the chemokine CXCL12.'] |
['Allopregnanolone is a neurosteroid produced in the brain that can alter the excitability of the CNS. Neurosteroids have neuroprotective properties, and their elevation in response to stress may protect the newborn brain following infection or hypoxia. Infection, particularly of the respiratory tract, may lead to episodes of hypoxia. Infection and hypoxia have been identified as factors contributing to neonatal morbidity and mortality.', 'To determine the effect of acute episodes of hypoxia alone or in combination with lipopolysaccharide (LPS) exposure on plasma and brain allopregnanolone concentrations in lambs 10-21 days old. Also, to examine plasma levels of cortisol and the cytokines, tumour necrosis factor-alpha and interleutkin-6 after these challenges.', 'Allopregnanolone concentrations in the brain were markedly increased after hypoxia. Hypoxia following prior LPS treatment resulted in greater increases in brain allopregnanolone concentrations compared to either the LPS or hypoxia treatment alone. Importantly, brain regions unaffected by LPS or hypoxia alone (thalamus/hypothalamus, cerebellum) showed significant increases of allopregnanolone content following the combined LPS and hypoxia treatments. Plasma tumour necrosis factor-alpha and interleukin-6 concentrations were increased after LPS treatment with and without hypoxia, but not by hypoxia alone. In contrast, plasma cortisol concentrations were increased after both stressors.'] |
['Magnesium supplementation is an effective protective method against cisplatin-induced nephrotoxicity (CIN); however, there are few reports regarding the mechanism of its nephroprotective effect. The aim of this study was to determine whether premedication with intravenous magnesium prevents CIN and to determine the relationship between its nephroprotective effect and serum magnesium level.', 'Fifty-eight patients with head and neck cancer who received cisplatin, docetaxel, and 5-fluorouracil (DCF) were retrospectively investigated. Grade 2 or more serum creatinine elevation was defined as CIN. The incidence of CIN was compared between a magnesium sulfate (20\xa0mEq, 2.46\xa0g) premedication group and a non-magnesium group during the first cycle and in all cycles.', 'CIN did not occur in any patients receiving magnesium premedication but did occur in 5 of 29 patients during the first cycle and in 6 patients during all subsequent cycles in patients who did not receive magnesium premedication. Furthermore, the variation of creatinine clearance was significantly worse in the non-magnesium group than in the magnesium premedication group from baseline. There was no difference in adverse effects or response rate between the two groups. Univariate analysis suggested that magnesium premedication significantly reduced the risk of CIN. On the other hand, serum magnesium depletion was seen in both groups to equal degrees despite supplementation.'] |
['Clinically evident renal disease (dialysis, history of renal insufficiency, or serum creatinine >2.0 mg/dL) is a known risk factor for mortality after thoracoabdominal aortic aneurysm repair. We extended this concept to the questions of whether subclinical renal disease is also a risk factor and how best to identify subclinical disease. We hypothesized that the glomerular filtration rate (GFR) would be a more sensitive determinant of renal function than serum creatinine alone.', 'Between 1991 and 2004, we repaired 1106 thoracoabdominal aortic aneurysms and descending thoracic aortic aneurysms. The median age was 67 years. There were 400 (36%) women and 706 (64%) men. We estimated GFR by using the Cockcroft-Gault equation. We divided baseline serum creatinine and baseline GFR into quartiles and estimated the association of the quartiles with 30-day postoperative mortality by chi2 testing. We further subdivided the population into patients with and without clinically evident renal disease and repeated the analysis in the patients without clinically apparent disease (n = 869).', 'Clinically apparent renal disease was highly associated with 30-day mortality (odds ratio, 3.2; P < .0001). In all patients, serum creatinine quartile and GFR quartile were also both highly significantly associated with 30-day mortality (P < .0001). In patients without clinically apparent renal disease, both creatinine and GFR predicted additional mortality, but GFR was a much stronger predictor (P < .02 for creatinine vs < .0001 for GFR). In these patients, mortality ranged from 5% in the best GFR quartile to 27% in the worst. Taken as continuous variables in logistic regression equations, serum creatinine had no discrimination in patients without clinical disease (P = .73), whereas GFR remained strong (P < .0001).'] |
['We use data from rural Nepal and South India to compare the prevalence of small-for-gestational-age (SGA) and neonatal mortality risk associated with SGA using different birth-weight-for-gestation reference populations.', 'We identified 46 reference populations in low-, middle-, and high-income countries, of which 26 met the inclusion criteria of being commonly cited and having numeric 10th percentile cut points published. Those reference populations were then applied to populations from two community-based studies to determine SGA prevalence and its relative risk of neonatal mortality.', 'The prevalence of SGA ranged from 10.5% to 72.5% in Nepal, and 12.0% to 78.4% in India, depending on the reference population. Females had higher rates of SGA than males using reference populations that were not sex specific. SGA prevalence was lowest when using reference populations from low-income countries. Infants who were both preterm and SGA had much higher mortality risk than those who were term and appropriate-for-gestational-age. Risk ratios for those who are both preterm and SGA ranged from 7.34-17.98 in Nepal and 5.29-11.98 in India, depending on the reference population.'] |
['Splenomegaly is a characteristic symptom of schistosome infection. Unlike the well known hepatic pathology of schistosomiasis, splenomegaly has received little scientific research and is generally considered to be a non-specific congestion caused by increased blood pressure within the venous sinuses. Moreover, to date, few studies have reported the deposition of schistosome eggs in the spleen. In a previous study, however, we observed that prolonged S. japonicum infections destroyed the structure of the lymphoid follicles in the spleen of mice at 8 weeks post-infection and found that eggs were frequently deposited in the spleen. These prior observations suggested a relationship between granulomas and splenic morphology which we investigate further in this study.', 'C57BL/6 mice were infected percutaneously with twenty cercariae of S. japonicum and sacrificed at different times post-infection. The number of eggs present in the homogenates of spleens and livers was quantified by light microscopy. Splenic pathology was observed by immunohistochemistry staining of paraffin-embedded sections. At 18 weeks post-infection the infected mice were divided into two groups (granulomatous spleens and non-granulomatous spleens). Serum antibodies and cytokines in the antigen- or mitogen-stimulated lymphocyte cultures were then determined by ELISA.', 'We found that eggs deposition in the spleens of infected mice occurred frequently but only occasionally led to granulomas formation. The lymphoid follicles within the granulomatous spleens maintained their structural integrity until 20 weeks post-infection, unlike the lymphoid follicles in spleens without egg granulomas. Mice with granulomatous spleens accompanied by lymphoid follicles exhibited a germinal center (GC)-like structure and had enhanced humoral immune responses. Splenocytes from granulomatous spleens also showed significantly elevated levels of Th2 cytokines during late infection stages.'] |
['Transforming growth factor beta is recognized as a major cytokine in extracellular matrix (ECM) pathobiology as occurs in diabetic nephropathy. While experimental studies have advanced a protective role of carnosine for diabetic complications, a link between carnosine, TGF-β and matrix accumulation remains to be elucidated. In the present study, we tested the hypothesis that L-carnosine inhibits TGF-β production and signalling, thereby reducing hyperglycaemia-associated ECM accumulation.', 'Human mesangial cells (MC) were cultured in high-glucose (HG, 25 mM D-glucose) medium alone or in HG medium to which 20 mM L-carnosine was added. Collagen VI (Col6) and fibronectin (FN) deposition and messenger RNA expression were studied. In addition, TGF-β production and activation of Smad1/5/8 (ALK1) and Smad2/3 (ALK5) pathways were assessed.', 'Under HG conditions, deposition of Col6 and FN were increased 1.4- and 1.6-fold. This was significantly inhibited on the protein and messenger RNA level by L-carnosine. TGF-β production increased under HG conditions but was completely normalized by addition of L-carnosine. Addition of exogenous TGF-β could not overcome the effect of L-carnosine on Col6 and FN expression, indicating additionally interference with TGF-β downstream signalling. Along the same line, L-carnosine reduced TGF-β-mediated Smad2 phosphorylation, suggesting an inhibitory effect on ALK5 signalling. ALK1 signalling remained unchanged. Under HG conditions, pharmacologic inhibition of ALK5 prevented Col6 accumulation but did not change FN deposition.'] |
['The optimal therapy for adult steroid-resistant nephrotic syndrome (SRNS) remains a therapeutic challenge. We investigated the efficacy and safety of tacrolimus as a promising regimen in Chinese adult patients.', 'A prospective, multicenter trial was conducted in 9 nephrology centers from 2006 to 2008, in patients with SRNS (defined as failure to respond to 1 mg/kg/day of prednisone for 8, and 16 weeks, in focal segmental glomerulosclerosis). Patients were treated with tacrolimus (TAC) plus prednisone for 12 months. TAC dose was titrated to achieve a target trough blood concentration of 5-10 ng/ml for the first 6 months and 4-6 ng/ml for the subsequent 6 months. The primary outcomes included complete or partial remission [complete remission (CR): proteinuria <0.3 g/24 h, with serum albumin ≥ 3.5 g/dl and stable renal function; partial remission (PR): proteinuria between 0.3 and 3.5 g/24 h and a decrease of at least 50 % from the baseline level, with serum albumin ≥ 3.0 g/dl and stable renal function]. Secondary end-points included relapse rate, changes of clinical parameters (proteinuria, serum albumin, and lipid profile) and adverse events.', 'Twenty-four patients with SRNS were enrolled. After 6 months of therapy, CR was achieved in 58.3 % of patients and PR in 16.7 %, yielding a final response rate of 75.0 %. The decrease in proteinuria was 43.1 ± 17.5 % after the first month of treatment (P < 0.001). Complete or PR was achieved in 6 of 8 patients with minimal change disease, 4 of 6 patients with mesangioproliferative glomerulonephritis (MsPGN), 6 of 7 patients with focal segmental glomerulosclerosis (FSGS), and all 2 patients with IgA nephropathy. Two patients (1 with MsPGN and 1 with FSGS) experienced relapses during the subsequent 6 months of follow-up. Adverse events included infection, hand tremor, diarrhea, acute reversible or persistent nephrotoxicity.'] |
['Liposuction-curettage (LC) is an effective surgical therapy option for axillary hyperhidrosis, with less scarring compared with radical excision of axillary skin. Although this method has proven to be effective, the treatment of nonresponders to minimally invasive surgery has not been previously defined. Whether these patients benefit from a second surgical procedure has not been evaluated so far.', 'To investigate efficacy and side-effects of a second LC with an aggressive rasping cannula in patients with insufficient prior surgery.', "Nineteen nonresponders to prior LC (13 female and six male) underwent a second LC with a rasping cannula. Gravimetry was performed before and 8 months after surgery. Side-effects, patient satisfaction, the surgeons' intraoperative evaluation and the Vancouver Scar Scale (VSS) before and after surgery were documented.", 'Sweat rates showed a reduction of 69% in 17 (89%) patients. Two patients (11%) did not respond to surgery. Eighty-four per cent of all patients were completely satisfied or satisfied with postoperative results. No severe side-effects were observed. The surgeon reported slightly increased difficulties during dissection of dermis from subcutaneous fat in three patients. Assessment of scars showed an excellent aesthetic outcome (mean VSS 0.79 before vs. 1.1 after surgery).'] |
['Thickening and reduplication of the tubular basement membrane have been reported as early events in diabetic nephropathy. In this study, we have examined the polar requirements of proximal tubular cells for the d-glucose-stimulated accumulation of fibronectin and the mechanism by which this occurred, with particular emphasis on the polyol pathway.', 'To determine the polarity of fibronectin generation in response to glucose, LLC-PK1 cells were grown on porous tissue culture inserts. Monolayer confluence was determined by serial measurement of transepithelial resistance. Confluent cells were growth arrested by serum deprivation, and all experiments were performed under serum-free conditions.', 'Application of 25 mm d-glucose to either the apical or basolateral aspect of LLC-PK1 cells led to fibronectin accumulation in the basolateral compartment. This reached statistical significance 24 hours following apical addition of glucose (2.6-fold increase compared with 5 mm d-glucose, P = 0.0025, N = 6 vs. N = 4 controls) and 12 hours after the basolateral addition of glucose (2.5-fold increase compared with 5 mm d-glucose, P = 0.03, N = 6 vs. N = 4 controls). Exposure of cells to glucose at either their apical or basolateral aspect leads to accumulation of intracellular glucose and polyol pathway activation, as assessed by sorbitol accumulation. The increase in fibronectin concentration in response to glucose was inhibited by the aldose reductase inhibitor sorbinil. At a dose of 100 micron sorbinil, there was a 59% inhibition of fibronectin accumulation in response to apical glucose (P = 0.004, N = 3 sorbinil vs. N = 4 controls) and a 66% inhibition in response to basolateral glucose (P = 0.008, N = 3 sorbinil vs. N = 4 controls) 48 hours after the addition of the inhibitor. Furthermore, fibronectin accumulation was also demonstrated following both the apical and basolateral addition of 1 mm sorbitol, but not following the addition of 25 mm galactose to either aspect of the cells. Following the addition of sorbitol, there was a 2. 8-fold increase in fibronectin 48 hours after apical stimulation (P = 0.01, N = 3 treated vs. N = 4 control) and a 2.27-fold increase following basolateral stimulation (P = 0.04, N = 3 treated vs. N = 4 control) at 24 hours.'] |
['Experimental animal study.', 'To investigate the neuroprotective efficacy of this magnesium in polyethylene glycol (PEG) formulation in a contusive model of cervical spinal cord injury (SCI).', 'Intravenously administered magnesium has been extensively investigated as a neuroprotective agent in animal models of SCI, stroke, and traumatic brain injuries, and has been evaluated in large scale clinical trials for the latter 2 indications. We have developed a novel formulation of magnesium chloride (MgCl₂) within PEG, and have previously demonstrated the neuroprotective benefit of this formulation in animal models of thoracic SCI.', 'Twenty-two Sprague Dawley rats underwent a unilateral cervical hemicontusion at C4-C5 and were randomized 2 hours later to either the MgCl₂ in PEG formulation, or normal saline. Each treatment was administered in 5 intravenous infusions spaced 6 hours apart. Behavioral recovery was assessed over 6 weeks, after which the cord was analyzed to measure the extent of gray matter and white matter sparing through the injury site.', 'In the horizontal ladder test, the percentage of forelimb errors made by the animals treated with MgCl₂ in PEG formulation was significantly lower than the saline-treated controls. Histologic analysis also revealed a significantly higher cumulative white matter sparing through the injury site in the MgCl₂ in PEG group.'] |
['Recent studies demonstrating a role for plasminogen activator inhibitor (PAI)-1 in cholestatic liver disease in mice suggested that tissue-type plasminogen activator (tPA) or urokinase plasminogen activator (uPA) might be important after biliary tract obstruction. We now demonstrate that blocking tPA exacerbates liver injury after bile duct ligation (BDL). tPA deficient mice have increased bile infarcts, increased TUNEL positive cells, increased neutrophil infiltration, reduced hepatocyte proliferation and reduced ductular reaction 72 hours after BDL compared to wild type mice. In addition, the protective and proliferative effects of plasminogen activator inhibitor 1 (PAI-1) deficiency after BDL are dramatically blocked by the tPA inhibitor tPA-STOP. One potential mechanism for these effects is that both tPA deficiency and tPA-STOP reduce hepatocyte growth factor (HGF) activation and c-Met phosphorylation in the liver after BDL. In support of this hypothesis, HGF treatment reverses the effects of tPA deficiency in mice. Furthermore, preferential tPA activation in areas of injury after BDL might occur because fibrin accumulates in bile infarcts and activates tPA.'] |
["Parental distress following the birth of a premature infant diminishes the parent's ability to be sensitive to the infant's cues, and this may affect infant developmental outcomes.", 'The present study examined the effects of maternal anxiety during infant hospitalization in the Neonatal Intensive Care Unit (NICU) on the interactive behavior of mothers with their very low birthweight (VLBW) children in toddlerhood.', 'A sample of 56 mothers and their VLBW infants were recruited in the NICU.', "During the infant's NICU stay, mothers completed a self-report measure of trait anxiety. These mothers and their infants were followed when the infants were 24 months corrected age, when mothers and their children were videotaped during free play at home. These videotapes were then coded using the Emotional Availability Scales.", 'Maternal anxiety was not found to be related to severity of neonatal illness. Maternal anxiety in the NICU was associated with less sensitivity and less structure in interaction with their toddlers at 24 months corrected age, even controlling for maternal education and child birthweight. Children of mothers with higher anxiety scores in the NICU were less likely to involve their mothers in their play at 24 months corrected age.'] |
["In this study, we sought to address changes in blood lymphocyte subpopulations and labial salivary gland (LSG) inflammation after belimumab treatment in patients with primary Sjögren's syndrome (pSS) and to identify predictors of response to treatment.", "Sequential blood lymphocyte subsets and LSG biopsies were analysed between week 0 (W0) and W28 in 15 patients with pSS treated with belimumab. Systemic response to treatment was defined as a decrease in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index score of ≥3 points at W28.", 'After belimumab, we observed a decrease in blood B lymphocytes primarily involving CD27-negative/immunoglobulin D-positive naïve B cells (p=0.008). Lymphocytic sialadenitis (focus score >1) that was present in 12 patients (80.0 %) before belimumab treatment became negative in 5 of them after treatment (p=0.03). The median (interquartile range) LSG B-cell/T-cell ratio decreased from 0.58 (0.5-0.67) to 0.50 (0.5-0.5) (p=0.06). B-cell activating factor (BAFF) staining was detected in 11 (78.6 %) of 14 patients before belimumab treatment compared with 7 (50.0 %) of 14 after belimumab therapy (p=0.10). The median percentage of BAFF-positive cells in foci significantly decreased from 27.5 % (10-40) to 5 % (0-20) (p=0.03). A systemic response was achieved in six patients (40 %). The only predictor of response was the presence of a low number of natural killer (NK) cells, both in blood (8.5 % [7-10] vs 11 % [9-21]; p=0.04) and in LSG (20.6/mm(3) [20.0-21.4] vs 30.0/mm(3) [25.0-100.0], p=0.003). Serum BAFF levels did not influence response to treatment.'] |
['Added transforming growth factor beta (TGFbeta) inhibits the proliferation of immature cardiomyocytes. We have now examined the hypothesis that suppression of endogenous TGFbeta signaling will boost the proliferative response (DNA synthesis) of cardiac myocytes to serum and/or to the mitogenic factor fibroblast growth factor-2 (FGF-2).', 'Overexpression of a kinase-deficient TGFbeta type II receptor (TGFbetaRIIDeltaKD) resulted in a 2.8-fold increase in cardiomyocyte DNA synthesis in serum-rich cultures, an effect requiring active FGFR-1 since it was not observed in the presence of excess kinase-deficient FGFR-1. This finding suggested that endogenous TGFbeta-TGFbetaRII suppressed endogenous FGFR-1-mediated signals that stimulate or are permissive for DNA synthesis. TGFbeta had no effect, however, on the FGF-2-induced acute stimulation of extracellular signal regulated kinase1/2. FGF-2, added in the absence or presence of TGFbeta inhibition, elicited a 3- or a 13-fold stimulation of DNA synthesis, respectively, pointing to a synergistic effect.'] |
['The study aimed to determine the risk of death or urgent transplant for patients who survived an initial 6 months on the outpatient heart transplant waiting list when criteria emphasizing reduced peak oxygen consumption are used for transplant candidate selection.', 'Waiting time is a key criterion for heart donor allocation. A recent single-center investigation described decreasing survival benefit from transplant for patients who survived an initial 6 months on the outpatient waiting list.', 'Kaplan-Meier survival analyses were performed for 80 patients from the Hospital of the University of Pennsylvania (HUP) listed from July 1986 to January 1991, and 132 patients from Columbia-Presbyterian Medical Center (CPMC) listed from September 1993 to September 1995. Survival from the time of outpatient listing for the entire group (ALL) was compared to subsequent survival from 6 months onward for those patients who survived the initial 6 months after placement on the outpatient list (6M). Both urgent transplant and left ventricular assist device implantation were considered equivalent to death; elective transplant was censored. RESULTS Survival for 6M was not significantly better than ALL at HUP (subsequent 12 months: 60+/-7 vs. 60+/-6% [mean+/-SD]; p = 0.89) nor at CPMC (subsequent 12 months: 60+/-6 vs. 48+/-5%; p = 0.35). Survival for 6M at both centers was substantially lower than survival following transplant from the outpatient list in the United States in 1995.'] |
['Glioblastoma (GBM) genomes feature recurrent genetic alterations that dysregulate core intracellular signaling pathways, including the G1/S cell cycle checkpoint and the MAPK and PI3K effector arms of receptor tyrosine kinase (RTK) signaling. Elucidation of the phenotypic consequences of activated RTK effectors is required for the design of effective therapeutic and diagnostic strategies.', 'Genetically defined, G1/S checkpoint-defective cortical murine astrocytes with constitutively active Kras and/or Pten deletion mutations were used to systematically investigate the individual and combined roles of these 2 RTK signaling effectors in phenotypic hallmarks of glioblastoma pathogenesis, including growth, migration, and invasion in vitro. A novel syngeneic orthotopic allograft model system was used to examine in vivo tumorigenesis.', 'Constitutively active Kras and/or Pten deletion mutations activated both MAPK and PI3K signaling. Their combination led to maximal growth, migration, and invasion of G1/S-defective astrocytes in vitro and produced progenitor-like transcriptomal profiles that mimic human proneural GBM. Activation of both RTK effector arms was required for in vivo tumorigenesis and produced highly invasive, proneural-like GBM.'] |
["Post-menopausal osteoporosis (PO) affecting a large fraction of elderly women, is triggered by the decline in 17β-estradiol (E2) level. Experimental studies in animal models and cell cultures have suggested that the fall in E2 might contribute to developing oxidative stress (OS) which in turn is believed to play an important role in PO pathogenesis. The scarcity of human studies focusing on this issue prompted us to investigate the effects of the reproductive and post-reproductive phase of women's life on OS and bone health.", 'Serum parameters of oxidative challenge (lipid hydroperoxides and protein advanced oxidation products) and antioxidant defence (total serum antioxidants levels) along with bone mineral density (BMD) at femoral neck and lumbar spine were assessed in a sample of 191 women (98 pre- and 93 post-menopausal, of whom 30 osteoporotic).', "Pearson's correlation analysis unveiled that spinal BMD was negatively correlated with lipid hydroperoxides in overall postmenopausal subsample (r=-0.251, p=0.012), while no significant link between these two variables was detected in women in reproductive age (r=-0.022, p=0.833). Noteworthy, stepwise multiple regression analysis showed that the association found in post-menopausal women retained significance after adjusting for potential confounding factors (p=0.001)."] |
['Synchronous activation of the Wnt signaling pathway, mostly because of loss of function of the APC tumor suppressor, and of the oncogenic KRAS-signaling pathway is very frequent in colorectal cancer and is associated with poor prognosis.', 'We have generated a compound transgenic mouse model, KRAS(V12G)/Apc(+/1638N), to recapitulate the human disease and compared it with single transgenic littermates.', 'Compound mutant mice are characterized by a 10-fold increase in tumor multiplicity and by accelerated tumor progression, resulting in strongly enhanced morbidity and mortality. Tumors from compound mutant mice proliferate faster and show decreased levels of apoptosis. Several lines of evidence indicate that the observed increase in tumor multiplicity and malignant transformation is caused by the synergistic activation of Wnt signaling in cells with oncogenic KRAS and loss-of-function Apc mutations. Activated KRAS is known to induce tyrosine phosphorylation of beta-catenin, leading to its release from E-cadherin at the adherens junction. This results in an increased beta-catenin pool in the cytoplasma, its subsequent translocation to the nucleus, and the transcriptional activation of Wnt downstream target genes. Accordingly, intestinal tumors from KRAS(V12G)/Apc(+/1638N) mice show a significant increase in cells with nuclear accumulation of beta-catenin when compared with Apc(+/1638N) animals. Moreover, Apc/KRAS-mutant embryonic stem cells show a significantly enhanced beta-catenin/T-cell factor-mediated transcriptional activation, accompanied by increased beta-catenin nuclear localization.'] |
['The study of faeces offers a unique opportunity to observe cooperation between the microbiome and the metabolism of mammalian hosts, an essential element in the study of the human metabolome. In the present study, a global metabolomics approach was used to identify metabolites differentially excreted in the faeces of cirrhotic patients compared to controls.', 'Seventeen cirrhotic patients and 24 healthy individuals were recruited. Faecal metabolites were detected through non-targeted reversed-phase ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry.', 'A total of 9215 peaks were detected. Using unequal variance t-tests, 2393 peaks were observed with P≤0.05, approximately 74.0% of which were due to decreased faecal metabolite concentrations in liver cirrhosis vs. healthy controls. Integrating multivariate data analyses, we identified six major groups of metabolites. Relative levels of identified metabolites were as follows: strong increase in lysophosphatidylcholines, aromatic amino acids, fatty acids, and acylcarnitines, and a dramatic decrease in bile acids and bile pigments.'] |
['To investigate YBX2 gene alterations in men with severe defects in spermatogenesis, including azoospermia or severe oligozoospermia, and protamine deregulation. MSY2 has been identified as a central component in the regulation of spermatogenesis in mice, but the potential role of its human orthologue, YBX2 or "Contrin," in human infertility is not known.', 'A prospective cohort study.', 'University infertility clinic and associated research laboratory.', 'A total of 288 men were evaluated. Diagnoses were made of complete azoospermia, severe oligozoospermia, and protamine deregulation, or men were of known paternity.', 'Deoxyribonucleic acid (from peripheral blood) and semen samples were collected and analyzed for gene mutations and semen parameters respectively.', 'YBX2 gene alterations.', 'YBX2 sequence analysis revealed 15 polymorphic sites, of which seven polymorphisms were present at a statistically higher frequency in one or both of the patient populations than in controls. Of these seven, two resulted in an amino acid substitution in the highly conserved cold shock domain and one resulted in a highly significant synonymous change in exon 8 of infertile patients. The frequency of single nucleotide polymorphisms was significantly elevated in patients with infertility, particularly in men with abnormal protamine expression.'] |
['In order to validate immature granulocytes as a universal biomarker, we have compared the clinical relevance of the proportion of immature granulocytes (IG%), measured using Sysmex XE-2100, with other biomarkers (white blood cell, C-reactive protein, lactate and procalcitonin).', 'This single center, retrospective study included 184 patients with sepsis admitted to an emergency department. Patients were classified into two groups: Uncomplicated sepsis and complicated sepsis (severe sepsis and septic shock). IG% and other biomarkers were evaluated and compared for predicting sepsis severity, overt disseminated intravascular coagulation (DIC) and 28 day mortality.', 'In multivariate analysis, only IG% (odd ratio [OR] 2.530, p = 0.004) and lactate (OR 4.500, p < 0.001) could discriminate between complicated and uncomplicated sepsis. The optimal cut-off value for IG% and lactate was 0.5% and 2.0 mmol/L, respectively. In subgroup analyses of complicated sepsis, IG% was related to overt DIC. However, no single biomarker could predict 28-day mortality.'] |
['X-linked adrenoleukodystrophy (ALD) is a metabolic, peroxisomal disease that results from a mutation in the ABCD1 gene. The most severe course of ALD progression is the cerebral inflammatory and demyelinating form of the disease, cALD. To date there is very little information on the cytokine mediators in the cerebral spinal fluid (CSF) of these boys.', 'Measurement of 23 different cytokines was performed on CSF and serum of boys with cerebral ALD and patients without ALD. Significant elevations in CSF IL-8 (29.3±2.2 vs 12.8±1.1 pg/ml, p\u200a=\u200a0.0001), IL-1ra (166±30 vs 8.6±6.5 pg/ml, p\u200a=\u200a0.005), MCP-1 (610±47 vs 328±34 pg/ml, p\u200a=\u200a0.002), and MIP-1b (14.2±1.3 vs 2.0±1.4 pg/ml, p<0.0001) were found in boys with cALD versus the control group. The only serum cytokine showing an elevation in the ALD group was SDF-1 (2124±155 vs 1175±125 pg/ml, p\u200a=\u200a0.0001). The CSF cytokines of IL-8 and MCP-1b correlated with the Loes MRI severity score (p\u200a=\u200a0.04 and p\u200a=\u200a0.008 respectively), as well as the serum SDF-1 level (p\u200a=\u200a0.002). Finally, CSF total protein was also significantly elevated in boys with cALD and correlated with both IL-8, MCP-1b (p\u200a=\u200a0.0001 for both), as well as Loes MRI severity score (p\u200a=\u200a0.0007).'] |
['The formation of cholesterol gallstones is a complex process involving contributions from genes and environmental factors. Although gallbladder inflammation is believed to be common during cholelithogenesis, the role of immunologic factors is unknown.', 'The role of adaptive immunity in cholesterol cholelithogenesis was analyzed utilizing immunocompetent Helicobacter spp.-infected and -uninfected BALB/c and congenic immunodeficient Rag2(-/-) (Rag) mice. Lymphocyte transfer studies were performed to determine which cellular subset was responsible for cholesterol gallstone formation. Also, gallbladder inflammation was quantified to determine the nature of the inflammatory response associated with cholelilithogenesis.', 'When fed a lithogenic diet for 8 weeks, wild-type mice developed significantly more cholesterol gallstones (27%-80% prevalence) than Rag mice ( approximately 5%, P < .05). Helicobacter spp.-infected BALB/cJ mice displayed statistically significant increases in cholesterol gallstone prevalence compared with uninfected mice (81% vs. 39%; P < .05). Transfer of splenocytes or T lymphocytes to Rag2(-/-) mice increased stone prevalence markedly (26% and 40% respectively; P < .05), whereas transfer of B cells was not appreciably cholelithogenic (13%). The adaptive immune response increased the expression of gallbladder Muc genes and accumulation of mucin gel. In addition, T cells and cholesterol monohydrate crystals induced proinflammatory gene expression in the gallbladder, which likely contributes to gallbladder dysfunction.'] |
['Placenta accreta is one of the most devastating pregnancy complications. We sought to compare outcomes between women with placenta accreta when diagnosed antenatally or intrapartum, and to define predictors of the antenatal diagnosis.', 'Retrospective case-control study.', 'University teaching hospital.', 'Twenty-four women with placenta accreta diagnosed antenatally and 20 women discovered intrapartum.', 'Chart review of historical and delivery-associated variables. Rates were compared between the groups.', 'Placenta accreta diagnosed antenatally or intrapartum.', 'Women with antenatal diagnosis had a lower estimated blood loss of a median of 4500ml (range 100-15000ml) compared with 7800ml (range 2500-17000ml, p=0.012) and required fewer units of packed red blood cells transfused (median 7; range 0-27 compared with 13.5; range 4-31, p=0.026). Nineteen (79%) women diagnosed antenatally had balloon catheter occlusion carried out during the cesarean section. Five (21%) had the entire placenta left in situ. There was no difference in the rate of surgical complications or duration of hospitalization. The clinical diagnosis among women with antenatal diagnosis was more often placenta percreta (p=0.013). The risk factor profile of women with antenatal diagnosis of placenta accreta included higher gravidity (p=0.014) and parity (p<0.0001), history of cesarean section (p=0.004), and placenta previa in the current pregnancy (p<0.001).'] |
['Osteoarthritis (OA) is a highly prevalent, disabling joint disease with no existing therapies to slow or halt its progression. Cartilage degeneration hallmarks OA pathogenesis, and pannexin 3 (Panx3), a member of a novel family of channel proteins, is upregulated during this process. The function of Panx3 remains poorly understood, but we consistently observed a strong increase in Panx3 immunostaining in OA lesions in both mice and humans. Here, we developed and characterized the first global and conditional Panx3 knockout mice to investigate the role of Panx3 in OA. Interestingly, global Panx3 deletion produced no overt phenotype and had no obvious effect on early skeletal development. Mice lacking Panx3 specifically in the cartilage and global Panx3 knockout mice were markedly resistant to the development of OA following destabilization of medial meniscus surgery. These data indicate a specific catabolic role of Panx3 in articular cartilage and identify Panx3 as a potential therapeutic target for OA. Lastly, while Panx1 has been linked to over a dozen human pathologies, this is the first in vivo evidence for a role of Panx3 in disease.'] |
['Several lines of evidence support the involvement of mannose-binding lectin (MBL) in stroke brain damage. The lectin pathway of the complement system facilitates thrombin activation and clot formation under certain experimental conditions. In the present study, we examine whether MBL promotes thrombosis after ischemia/reperfusion and influences the course and prognosis of ischemic stroke.', 'Middle cerebral artery occlusion/reperfusion was performed in MBL-deficient (n=85) and wild-type (WT; n=83) mice, and the brain lesion was assessed by MRI at days 1 and 7. Relative cerebral blood flow was monitored up to 6 hours after middle cerebral artery occlusion with laser speckle contrast imaging. Fibrin(ogen) was analyzed in the brain vasculature and plasma, and the effects of thrombin inhibitor argatroban were evaluated to assess the role of MBL in thrombin activation.', 'Infarct volumes and neurological deficits were smaller in MBL knockout mice than in WT mice. Relative cerebral blood flow values during middle cerebral artery occlusion and at reperfusion were similar in both groups, but decreased during the next 6 hours in the WT group only. Also, the WT mice showed more fibrin(ogen) in brain vessels and a better outcome after argatroban treatment. In contrast, argatroban did not improve the outcome in MBL knockout mice.'] |
['To evaluate the association between genetic variants in Ser-Arg (SR) protein-coding genes and the susceptibility of nonobstructive azoospermia (NOA) in Chinese men.', 'Case-control study.', 'State Key Laboratory of Reproductive Medicine in Nanjing Medical University conducted the genotyping and examined the expression levels of genes.', 'The study included 962 NOA patients and 1,931 control subjects.', 'None.', 'Genotyping of 16 single-nucleotide polymorphisms (SNPs) of eight "canonic" SR protein-coding genes were performed with the use of the Illumina Infinium Beadchip platform. Odds ratios were calculated by logistic regression analysis in the additive model. Expression levels were measured by quantitative reverse-transcription polymerase chain reaction.', 'Rs17431717 near SFRS9 and rs12046213 near SFRS4 were significantly associated with a decreased risk of NOA, whereas rs10849753 near SFRS9 and rs6103330 in SFRS6 were associated with an increased risk of NOA. Of the two SNPs in SFRS9, only rs17431717 remained significant after conditioning on another. Combined analysis of three promising SNPs (rs17431717, rs12046213, and rs6103330) showed that compared with individuals with "0-2" risk alleles, those carrying "3," "4," and "≥ 5" risk alleles had 1.22-, 1.38-, and 1.90-fold increased risk of NOA, respectively.'] |
['A biomechanical study of facet joint pressure after total disc replacement using cadaveric human cervical spines during lateral bending and axial torsion.', 'The goal was to measure the contact pressure in the facet joint in cadaveric human cervical spines subjected to physiologic lateral bending and axial torsion before and after implantation of a ProDisc-C implant.', 'Changes in facet biomechanics can damage the articular cartilage in the joint, potentially leading to degeneration and painful arthritis. Few cadaveric and computational studies have evaluated the changes in facet joint loading during spinal loading with an artificial disc implanted. Computational models have predicted that the design and placement of the implant influence facet joint loading, but limited cadaveric studies document changes in facet forces and pressures during nonsagittal bending after implantation of a ProDisc. As such, little is known about the local facet joint mechanics for these complicated loading scenarios in the cervical spine.', 'Seven osteoligamentous C2-T1 cadaveric cervical spines were instrumented with a transducer to measure the C5-C6 facet pressure profiles during physiological lateral bending and axial torsion, before and after implantation of a ProDisc-C at that level. Rotations at that level and global cervical spine motions and loads were also quantified. RESULT.: Global and segmental rotations were not altered by the disc implantation. Facet contact pressure increased after implantation during ipsilateral lateral bending and contralateral torsion, but that increase was not significant compared with the intact condition.'] |
['To assess the intraocular pressure (IOP) lowering mechanism of deep sclerectomy with collagen implant (DSCI), a non-penetrating glaucoma surgery.', 'Nine eyes of nine patients with medically uncontrolled open angle glaucoma underwent DSCI. Ultrasound biomicroscopy (UBM) of the sclerectomy site was performed 1 month after surgery. The following factors were assessed: length and height of collagen implant, and thickness of the residual trabeculocorneal membrane.', 'Postoperative IOP decreased significantly in all nine eyes from a preoperative mean value of 25.8 (SD 4.8) mm Hg to a postoperative (1 month) mean value of 11.3 (6.3) mm Hg (p = 0.001). In all nine eyes, UBM at 1 month after surgery showed a subconjunctival filtration through the thin trabeculocorneal membrane and through the scleral flap around the collagen implant. In four cases, a hypoechoic area in the suprachoroidal space was observed and might represent ciliary body detachment or be due to suprachoroidal drainage of aqueous humour through the thin deep scleral wall. At 1 month after surgery the mean trabeculocorneal membrane thickness was 110.1 (16.8) microns, and the mean length and height of the collagen implant were 2.3 (0.1) mm and 1.1 (0.1) mm respectively.'] |
['Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration.', 'Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis.', 'The serum level of patients (IL-18) increased significantly with the grade of IVD degeneration. There was a dramatic alteration in IL-18 level between the advanced degeneration (Grade III to V) group and the normal group (p = 0.008) Furthermore, IL-18 induced upregulation of the catabolic regulator MMP13 and downregulation of the anabolic regulators aggrecan, type II collagen, and SOX6 at 24 hours, contributing to degradation of disc matrix enzymes. However, BMP-2 antagonised the IL-18 induced upregulation of aggrecan, type II collagen, and SOX6, resulting in reversal of IL-18 mediated disc degeneration.'] |
['To asses the effects of seminal plasma on sperm function.', 'Retrospective case-control study.', 'University hospital.', 'One hundred fourteen infertile men.', 'Acrobeads Test scores (0-4) and measurement of interleukin (IL)-6, soluble IL-6 receptor, epidermal growth factor, insulin-like growth factor-I (IGF-I), transforming growth factor-beta I, superoxide dismutase, calcitonin, and macrophage migration inhibitory factor (MIF) levels in seminal plasma.', 'Kruskal-Wallis test to compare the concentrations of substances as a nonparametric test for differences among Acrobeads Test scores and a multivariable logistic regression model to find independent risk factors associated with abnormal Acrobeads Test results.', 'The Acrobeads Test score was 0 for 7 samples, 1 for 20 samples, 2 for 18 samples, 3 for 28 samples, and 4 for 41 samples. Age, abstinence period, and semen parameters, except for sperm motility and percentage of sperm with abnormal morphology, had no effect on the Acrobeads Test results. Concentrations of IGF-I and MIF were significantly higher in patients with abnormal Acrobeads Test results. Multivariate analysis indicated that MIF and IGF-I were significantly associated with abnormal Acrobeads Test results (scores 0 to 1).'] |
['Diabetic women are five times more likely to develop congestive heart failure compared with two fold for men. The underlying mechanism for this gender difference is not known. Here we investigate the molecular mechanisms responsible for this female disadvantage and attempt safeguarding cardiomyocytes viability and function through restoration of pro-survival Pim-1.', 'Diabetes was induced by injection of streptozotocin in CD1 mice of both genders. Functional and dimensional parameters measurement using echocardiography revealed diastolic dysfunction in female diabetic mice within 8 weeks after STZ-induced diabetes. This was associated with significant downregulation of pro-survival Pim-1 and upregulation of pro-apoptotic Caspase-3, microRNA-1 and microRNA-208a. Male diabetic mice did not show any significant changes at this time point (P\u2009<\u20090.05 vs. female diabetic). Further, the onset of ventricular remodelling was quicker in female diabetic mice showing marked left ventricular dilation, reduced ejection fraction and poor contractility (P\u2009<\u20090.05 vs. male diabetic at 12 and 16 weeks of STZ-induced diabetes). Molecular analysis of samples from human diabetic hearts confirmed the results of pre-clinical studies, showing marked downregulation of Pim-1 in the female diabetic heart (P\u2009<\u20090.05 vs. male diabetic). Finally, in vitro restoration of Pim-1 reversed the female disadvantage in diabetic cardiomyocytes.'] |
['Infants of diabetic mothers have been characterized by macrosomia due to hyperinsulinism. A relation has been observed between circulating levels of leptin and the intrauterine growth pattern.', 'We studied the leptin and insulin concentrations in the cord blood of 29 newborn infants of mothers with type 1 diabetes (iT1DM), 70 newborn infants of mothers with gestational diabetes and 105 newborn infants of nondiabetic mothers.', 'There were significant differences (p < 0.001) between the 3 groups with the highest leptin levels 24.9 microg/l (range 1.7-94.1) in infants of mothers with iT1DM and the second-highest levels 14.0 microg/l (range 2.6-74.9) in infants of mothers with gestational diabetes (iGDM), whereas the control infants had the lowest leptin levels 10.0 microg/l (range 0.10-45.9). Girls had higher leptin concentrations than boys among the iT1DM and control infants. The insulin concentrations were 18.1 mU/l (range 1.9-123.3), 6.1 mU/l (range 1.1-51.4) and 3.6 mU/l (range 0.5-21.5) in the 3 groups (p < 0.001), respectively. A significant correlation was observed between leptin and insulin concentrations in iGDM and control infants (r = 0.51; p < 0.001 and r = 0.25; p < 0.05). Both absolute and relative birth weights correlated with leptin levels in all 3 groups (r = 0.60, p = 0.01 and r = 0.51, p = 0.05 in iT1DM; r = 0.51 and 0.56, p < 0.001 in iGDM and r = 0.42 and 0.59, p < 0.001 in control infants).'] |
['Kirsten-RAS (KRAS) mutations play an important role in the carcinogenesis of a subset of lung adenocarcinomas and are associated with poorer prognosis.', 'To investigate the relationship of KRAS mutation status to the histologic subtype of adenocarcinoma according to the recent classification, patient demographics, tumor size, predominant histologic subtype, nodal status, and visceral pleural invasion, in an attempt to uncover the reason for the worse prognosis associated with KRAS mutation.', 'A total of 187 consecutive resected lung adenocarcinomas from our institution from 2008 to 2011 that were diagnosed according to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification and screened for KRAS mutations were included in the study.', 'A total of 32% of the adenocarcinomas harbored the KRAS mutation. The median age in the KRAS mutation group was 69 years (range, 43-86 years), and male to female ratio was 1:2.3. The proportion of heavy smokers was significantly higher in tumors with KRAS mutation compared with wild type (83% versus 62%; P = .01). A total of 27% of tumors with KRAS mutation had pleural invasion versus 11% of tumors without KRAS mutation (P = .009). A total of 59 tumor samples were positive for KRAS mutation (25 for G12C, 14 for G12A, 8 for G12V, 7 for G12D, 3 for G12S, and 1 for G12T), and only 3 tumors harbored codon 13 mutations (G13C). Two tumors had double mutations.'] |
['Biomarkers of endothelial dysfunction, inflammation and coagulation are associated with atherosclerosis and cardiovascular disease, but their association and possible predictive value remain controversial among HIV-1-infected individuals. We sought to investigate the association of seven biomarkers with first-time myocardial infarction (MI) in an HIV-1-infected population.', 'A matched case-control study of 54 cases and 54 controls.', "We compared 54 HIV-1-infected patients with verified first-time MI and 54 HIV-1-infected controls matched for age, duration of antiretroviral therapy, sex, smoking and no known cardiovascular disease. Levels of high-sensitivity C-reactive protein, soluble endothelial selectin, soluble vascular cell adhesion molecule, soluble intercellular adhesion molecule, matrix metalloprotease 9, myeloperoxidase, and plasminogen activator inhibitor 1 (PAI-1) were measured using a Luminex assay in plasma samples from routine visits both 12 and 2 months prior to the case patient's MI.", 'The two groups had similar HIV characteristics and traditional cardiovascular risk factors. In univariate analysis, PAI-1 levels were associated with MI, whereas none of the other markers showed any association.In multivariate analyses adjusting for the D:A:D risk score, HIV viral load and high-sensitivity C-reactive protein, PAI-1 levels in the highest quartile were associated with a six to seven-fold increased risk of MI in both samples.'] |
['Endoscopic injection of stabilized nonanimal hyaluronic acid/dextranomer gel is an established treatment for vesicoureteral reflux in children. We performed a subgroup analysis to assess this treatment in reflux associated with bladder dysfunction.', 'Of 308 consecutive children treated endoscopically with stabilized nonanimal hyaluronic acid/dextranomer gel for dilating vesicoureteral reflux 54 were observed retrospectively to have bladder dysfunction. Initial followup consisted of voiding cystourethrogram at 3 and 12 months after injection, with positive response defined as reflux grade 0 or I. At 7 to 12 years following treatment patient charts were checked for urinary tract infections and bladder dysfunction, and a followup survey (postal questionnaire) was administered.', 'A positive response to therapy (cure) was observed in 45 children (83%) after 1 to 3 endoscopic treatments. Concurrently, bladder dysfunction had resolved in 32 patients (59%). After the last stabilized nonanimal hyaluronic acid/dextranomer gel implantation 45 patients (83%) were free of urinary tract infections. Questionnaire results were similar to chart based findings. Stabilized nonanimal hyaluronic acid/dextranomer gel implantation was well tolerated, with no associated complications.'] |
['Plant growth depends on both cell division and cell expansion. Plant hormones, including brassinosteroids (BRs), are central to the control of these two cellular processes. Despite clear evidence that BRs regulate cell elongation, their roles in cell division have remained elusive.', 'Here, we report results emphasizing the importance of BRs in cell division. An Arabidopsis BR biosynthetic mutant, dwarf7-1, displayed various characteristics attributable to slower cell division rates. We found that the DWARF4 gene which encodes for an enzyme catalyzing a rate-determining step in the BR biosynthetic pathways, is highly expressed in the actively dividing callus, suggesting that BR biosynthesis is necessary for dividing cells. Furthermore, dwf7-1 showed noticeably slower rates of callus growth and shoot induction relative to wild-type control. Flow cytometric analyses of the nuclei derived from either calli or intact roots revealed that the cell division index, which was represented as the ratio of cells at the G2/M vs. G1 phases, was smaller in dwf7-1 plants. Finally, we found that the expression levels of the genes involved in cell division and shoot induction, such as PROLIFERATING CELL NUCLEAR ANTIGEN2 (PCNA2) and ENHANCER OF SHOOT REGENERATION2 (ESR2), were also lower in dwf7-1 as compared with wild type.'] |
['Human cytomegalovirus (CMV) infection is associated with inferior survival in renal transplant patients, and ganciclovir (GCV) prophylaxis is associated with improved survival. In a murine CMV (MCMV) renal transplantation model, ganciclovir prophylaxis improved innate infiltrates and allograft damage during the period of prophylaxis. In this study, late effects were examined after the discontinuation of prophylaxis.', 'MCMV D+/R- and D-/R- allogeneic transplants were performed with cyclosporine immunosuppression. One D+/R- cohort received ganciclovir prophylaxis for 14 days after transplantation followed by 28 days without ganciclovir. At 42 days after transplantation, grafts were analyzed for histologic tissue damage and immune infiltrates. Another D+/R- cohort was treated with anti-NK1.1 antibodies for 14 days after transplantation and compared with animals without natural killer (NK) cell depletion.', 'At day 42, MCMV-infected transplants had higher damage scores (15.6±0.6) compared with uninfected transplants (8.3±0.9; P<0.01), which improved in ganciclovir-treated allografts (9.5±1.4). MCMV-infected grafts contained greater frequencies of NK cell and myeloid infiltrates compared with uninfected grafts (P<0.05), which decreased in the ganciclovir-treated grafts. NK cell depletion improved allograft histology of MCMV-infected grafts.'] |
['We reported that obesity was associated with increased arterial compliance in children, possibly due to accelerated vascular maturation. Here, we explored the additional burden of type 2 diabetes (T2DM) on vascular function in children.', 'Fifty normal weight [body mass index (BMI) 25-75%], 58 obese (BMI\u2009≥\u200995%), and 34 children with T2DM diagnosed by American Diabetes Association (ADA) criteria ages 10-18 yr were studied. Large and small artery elasticity (LAEI and SAEI, respectively) were measured by diastolic pulse-wave contour analysis.', 'SAEI was 27% higher in children with T2DM compared to normal weight children (p\u2009=\u20090.005). Mean LAEI for those with T2DM not different from either group. In the group with T2DM, both SAEI and LAEI increased with age up to 16\u2009yr, but declined thereafter. The strongest multivariable model predicting SAEI in children with T2DM combined lean mass, systolic blood pressure (SBP), and glucose (r2 \u2009=\u20090.59); for predicting LAEI, the strongest model included height, SBP, and low-density lipid-cholesterol (r2 \u2009=\u20090.61).'] |
['The acceptance of microarray technology in regulatory decision-making is being challenged by the existence of various platforms and data analysis methods. A recent report (E. Marshall, Science, 306, 630-631, 2004), by extensively citing the study of Tan et al. (Nucleic Acids Res., 31, 5676-5684, 2003), portrays a disturbingly negative picture of the cross-platform comparability, and, hence, the reliability of microarray technology.', "We reanalyzed Tan's dataset and found that the intra-platform consistency was low, indicating a problem in experimental procedures from which the dataset was generated. Furthermore, by using three gene selection methods (i.e., p-value ranking, fold-change ranking, and Significance Analysis of Microarrays (SAM)) on the same dataset we found that p-value ranking (the method emphasized by Tan et al.) results in much lower cross-platform concordance compared to fold-change ranking or SAM. Therefore, the low cross-platform concordance reported in Tan's study appears to be mainly due to a combination of low intra-platform consistency and a poor choice of data analysis procedures, instead of inherent technical differences among different platforms, as suggested by Tan et al. and Marshall."] |
['To investigate the association between metabolic syndrome (MS) and disease activity in patients with rheumatoid arthritis (RA).', 'Siriraj Rheumatoid Arthritis registry is a prospective cohort study establishing since May 2011. A total of 267 patients who had complete data in February 2015 were included in these analyses. All clinical and laboratory data related to disease activity, functional status, and parameters of MS according to the 2001 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) were collected. Univariate and backward stepwise multivariate analyses were performed to identify factors associated with MS.', 'Most (88%) were female with the mean age±standard deviation of 59±11.1 years old. MS was found in 43 patients (16%). Patients with MS had a significantly lower proportion of patients with remission (time-adjusted mean of disease activity score 28 or DAS28<2.6) than those with non-MS (2.3% vs. 16.5%, P=0.02). Multiple logistic regression analysis identified 3 independent factors associated with MS including body mass index [OR 1.2, 95% CI 1.1 to 1.3], educational level≤12 years [OR 5.92, 95% CI 1.47 to 23.83], and disease remission [OR 0.11, 95% CI 0.01 to 0.93]. This model correctly predicted 84% of cases.'] |
['There is a lot of inter-individual variation in the rotational anatomy of the distal femur. This study was set up to define the rotational anatomy of the distal femur in the osteo-arthritic knee and to investigate its relationship with the overall coronal alignment and gender.', 'CT-scans of 231 patients with end-stage knee osteo-arthritis prior to TKA surgery were obtained. This represents the biggest series published on rational geometry of the distal femur in literature so far.', 'The posterior condylar line (PCL) was on average 1.6° (SD 1.9) internally rotated relative to the surgical transepicondylar axis (sTEA). The perpendicular to trochlear anteroposterior axis (⊥TRAx) was on average 4.8° (SD 3.3°) externally rotated relative to the sTEA. The relationship between the PCL and the sTEA was statistically different in the different coronal alignment groups (p < 0.001): 1.0° (SD 1.8°) in varus knees, 2.1° (SD 1.8°) in neutral knees and 2.6° (SD 1.8°) in valgus knees. The same was true for the ⊥TRAx in these 3 groups (p < 0.02).There was a clear linear relationship between the overall coronal alignment and the rotational geometry of the distal femur. For every 1° in coronal alignment increment from varus to valgus, there is a 0.1° increment in posterior condylar angle (PCL vs sTEA).'] |
['Hepatocellular carcinoma is one of the most common malignancies worldwide. The only curative treatment is surgery. As hepatocellular carcinoma is often associated with liver cirrhosis, patients are at risk for postoperative liver failure. In the recent years, platelets are thought to play an important role in liver regeneration.The aim of this study was to discover the relevance of postoperative platelet counts after liver resection for hepatocellular carcinoma.', 'Data of 68 patients who underwent liver resection for hepatocellular carcinoma between July 2007 and July 2012 in a single centre were analysed. Postoperative morbidity and mortality were evaluated in regard to postoperative platelet counts. Comparative analysis between patients with platelet counts ≤100 2x109/ l and >100 x109/ l at d1 was performed in regard to postoperative outcome.', 'Within this cohort, 43 patients (63%) suffered from histologically proven liver cirrhosis. Postoperative mortality was statistically significant associated with postoperative reduced platelet counts. Comparative analysis showed significantly elevated postoperative bilirubin levels and lower prothrombin time in patients with platelet counts ≤ 100 1x109/ l at d1.'] |
['Familial hypercholesterolaemia (FH) is characterized by premature coronary heart disease (CHD). However, the incidence of CHD varies considerably among FH patients. Genetic variation in the renin-angiotensin-aldosterone system (RAAS) and the adrenalin/noradrenalin system may be of importance in determining the CHD risk in FH, because of their involvement in CHD. We investigated the association between CHD risk and combined genetic variation in the RAAS and adrenalin/noradrenalin system.', 'In 2190 FH patients, we genotyped six RAAS polymorphisms and five adrenalin/noradrenalin polymorphisms. For each patient, we calculated two gene-load scores by counting the number of risk genotypes within each pathway. Four of the six RAAS polymorphisms and none of the polymorphisms in the adrenalin/noradrenalin system were significantly associated with CHD (P < 0.05). The RAAS gene-load score was significantly associated with CHD (P(linear trend) < 0.001): in patients with a gene-load score of 5 or 6, the CHD risk was 2.3 times as high as in patients with a score of 0 or 1. The gene-load score of the adrenalin/noradrenalin system was not associated with CHD.'] |
["About 80% of patients with Crohn's disease (CD) require bowel resection and up to 65% will undergo a second resection within 10 years. This study reports clinical risk factors for resection surgery (RS) and repeat RS.", 'Retrospective cohort study, using data from patients included in the Swiss Inflammatory Bowel Disease Cohort. Cox regression analyses were performed to estimate rates of initial and repeated RS.', 'Out of 1,138 CD cohort patients, 417 (36.6%) had already undergone RS at the time of inclusion. Kaplan-Meier curves showed that the probability of being free of RS was 65% after 10 years, 42% after 20 years, and 23% after 40 years. Perianal involvement (PA) did not modify this probability to a significant extent. The main adjusted risk factors for RS were smoking at diagnosis (hazard ratio (HR) = 1.33; p = 0.006), stricturing with vs. without PA (HR = 4.91 vs. 4.11; p < 0.001) or penetrating disease with vs. without PA (HR = 3.53 vs. 4.58; p < 0.001). The risk factor for repeat RS was penetrating disease with vs. without PA (HR = 3.17 vs. 2.24; p < 0.05).'] |
['Prognosis of long-term motor outcome of acute stroke patients with severe motor impairment is difficult to determine.', 'Our primary goal was to evaluate the prognostic value of corticospinal tract (CST) injury on motor outcome of the upper limb compared with motor impairment level and lesion volume.', 'In all, 10 acute stroke patients with moderately severe to severe motor impairment of the upper limb underwent diffusion tensor imaging (DTI) and testing of upper limb strength and dexterity at acute, subacute, and chronic poststroke time points. A density-weighted CST atlas was constructed using DTI tractography data from normal participants. This CST atlas was applied, using a largely automated process, to DTI data from patients to quantify CST injury at each time point. Differences in axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) of the ipsilesional CST relative to the contralesional CST were measured.', 'Acute loss in CST AD correlated most strongly and significantly with subacute and chronic strength and dexterity and remained significant after adjusting for acute motor impairment or lesion volume. Subacute loss in CST FA correlated most strongly with chronic dexterity, whereas subacute behavioral measures of limb strength correlated most strongly with chronic strength measures.'] |
['Many ambulatory sleep apnea monitoring devices are equipped with software which allows an automated analysis of data as well as a visual analysis.', 'The Merlin system which records heart rate, snoring sound, efforts, oronasal flow, body position and oxygen saturation was investigated to identify proper parameter settings for the automated analysis and to compare the automated with the visual analysis in patients with mild obstructive sleep apnea syndrome (OSAS). Sensitivity and specificity of the visual and automated analysis of ambulatory monitoring in comparison with visual polysomnographic (PSG) analysis were determined.', 'First, we tried to find the optimal parameters for the automated analysis, using 7 different settings in 17 OSAS patients. Furthermore, we applied the optimized setting to 66 OSAS patients who were admitted (age 50.9 +/- 9.9 years, BMI 32.9 +/- 5 kg/m(2)), and compared the results with the visual analysis of raw data. The patients slept for one night in the sleep laboratory with Merlin and PSG simultaneously to compare the visual and automated analysis of Merlin data with results from the visual analysis of PSG. Automated analysis leads to an underestimation of the respiratory disturbance index (RDI; p < 0.001) compared with both the visual analysis and results of PSG. Using a cutoff level of 5 apneas and hypopneas/h for the diagnosis of OSAS, the sensitivity of Merlin with the automated analysis is 40.6% and the specificity is 100%. With a cutoff level of 15/h, sensitivity and specificity rose to 91.3 and 100%, respectively, which is comparable to the visual analysis.'] |
['To explore the molecular mechanism of apoptosis of the human umbilical vein endothelial cells (HUVECs) induced by burn serum and subeschar tissue fluid.', 'In vitro cultured HUVECs were randomly divided into A (treated by normal serum, n = 6), B (treated by burn serum, n = 6) and C (treated by subeschar tissue fluid, n = 6) groups. The change in cellular nuclear morphology was determined by Hochst 33258 fluorescent staining, and the apoptotic rate was calculated at 24th and 36th post treatment hours (PTHs). The DNA ladder strips were observed with agarose electrophoresis at 12th and 24th PTH. The activity of caspase-3, 8, 9 was assayed by caspase colorimetric assay kit at 12 PTH.', 'It was found that nuclei appeared to be condensed and highly fluorescent granular in form in B and C groups. The nucleic apoptotic rate in B and C groups was (38.9 +/- 7.3)% and (49.5 +/- 6.5)%, respectively, which was evidently higher than that in A group (P < 0.01). The DNA ladder strips could be found by agarose electrophoresis in B and C groups. The activity of caspase-3, 8, 9 in B and C groups was significantly higher than that in A group after 12 PTHs (P < 0.01).'] |
['Sleep changes are frequent in stroke patients and predict a poor outcome. It remains unclear how sleep influences stroke evolution and recovery. We assessed effects of sleep disruption on brain damage and on the expression of axon sprouting genes after focal cerebral ischemia in rats.', '12 h after ischemia induced by occlusion of the middle cerebral artery, rats were subjected to sleep disruption including sleep deprivation for 12h (SDpv12h) and sleep disturbances (SDis) by SDpv12h for consecutive 3 days. Control groups included ischemia without SDpv12h or SDis, sham surgery plus SDis and sham surgery without SDis. Sleep changes were evaluated based on EEG and EMG recordings.', 'SDpv12h increased the infarct volume by 40% (SDpv12h 82.8 +/- 10.9 vs. control 59.2 +/- 13.9 mm3, P = 0.008) and SDis by 76% (SDis 58.8 +/- 20.4 vs. control 33.8 +/- 6.3 mm3, P = 0.017). SDpv12h also increased the number of damaged cells, visualized by TUNEL staining, by 137% (SDpv12h 46.8 +/- 15 vs. control 19.7 +/- 7.7/mm2, P < 0.001) and SDis by 219% (SDis 32.9 +/- 13.2 vs. control 10.3 +/- 2.5/mm2, P = 0.002). In addition, SDis significantly elevated the expression of the axonal extension inhibitory molecule neurocan (SDis 14.3 +/- 0.4 vs. control 6.2 +/- 0.1-fold of change, P < 0.001) in the injured hemisphere.'] |
['We reviewed the issue of stem cells and therapeutic angiogenesis in the treatment of peripheral vascular disease.', 'MEDLINE (1997-2008) with the following search terms: "stem cell therapy," "endothelial progenitor cells," "peripheral blood mononuclear cells," and "peripheral vascular disease." Relevant published papers involving the above search terms, preclinical studies, and clinical trials using stem cells and progenitors for the treatment of peripheral occlusive vascular disease were included.', 'Transplantation of bone marrow-derived progenitor cells or peripheral blood mononuclear cells promotes tissue angiogenesis, as has already been explored in preclinical studies; angiogenesis can also be sustained using genetic, protein therapeutic approaches. Engineered scaffolding with stem cells is a further strategy, which is still in its infancy. The treatment of patients with severe peripheral arterial disease is generally reported as a series of case reports; all studies generally show an improvement in clinical symptoms, e.g., rest pain and pain-free walking time, as well as transcutaneous oxygen pressure, without any important adverse reactions. The few clinical trials also report similar encouraging results. All the studies have their shortcomings, including absence of control groups and objective evaluation of the results of treatments as well as short-term follow-up.'] |
['Human colonization with Helicobacter pylori increases the risk for distal gastric adenocarcinoma, possibly by altering gastric epithelial cell cycle events and/or gastrin secretion. This study aimed to determine whether H. pylori virulence-related characteristics affect apoptosis, proliferation, and gastrin levels in a rodent model of gastric adenocarcinoma.', 'Mongolian gerbils were challenged with H. pylori wild-type or isogenic cagA(-) and vacA(-) mutants, and apoptotic and proliferating cells were identified by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and proliferating cell nuclear antigen immunohistochemistry, respectively. Serum gastrin levels were determined by radioimmunoassay.', 'Gastric epithelial cell turnover was no different after infection with the wild-type, cagA(-), or vacA(-) strains. H. pylori infection significantly increased antral apoptosis 2-4 weeks after challenge, before apoptotic indices decreased to baseline. In contrast, antral proliferation rates were significantly higher 16-20 weeks after inoculation, but then decreased by 40 weeks. Antral proliferation was significantly related to serum gastrin levels, whereas antral apoptosis was inversely related to acute inflammation and lymphoid follicles.'] |
['To quantify right ventricular (RV) function in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after pulmonary endarterectomy (PEA).', 'Out of 33 patients, 16 were evaluated clinically and with echocardiography (conventional and myocardial deformation parameters) before PEA (preop) and at 1 week, 1 month, 3 months and 6 months after PEA. RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE) as well as mid-apical and basal peak ejection strain (S) and strain rate (SR) of the RV free wall were measured. Left ventricular (LV) apical lateral wall motion was regarded as indicating changes in overall heart rocking motion (RM). Heart catheterisation was performed before, within 1 week and at 6 months after PEA.', 'Clinical and haemodynamic parameters improved significantly after PEA. This correlated with the improvement in RVFAC, S and SR. TAPSE, on the other hand, showed a biphasic response (14.5 (4) mm preop, 8.5 (2.7) mm at 1 week and 11 (1.5) mm at 6 months). Changes in LV apical motion explain this finding. At baseline, TAPSE was enhanced by rocking motion of the heart as a result of the failing RV. Unloading the RV by PEA normalised the rocking motion and TAPSE decreased.'] |
['Caveolin-1 (CAV1) is an important structural component of cellular caveolae involved in cell signaling. CAV1 gene on/off regulatory mechanism in multiple diseases, including cancer is not clearly understood. The tumor suppressor versus oncogene paradox of CAV1 during tumor development tempted us to investigate the role for the epigenetic drift of CAV1 gene regulation.', 'We have analyzed CAV1 gene expression and associated epigenetic marks (DNA methylation and histone 3 modifications) in the CAV1 promoter in two colon cancer cell lines, under treatment with well established epigenetic modulators, AZA, SAM, TSA and SFN at varying concentrations. CAV1 gene promoter DNA methylation and histone modifications were analyzed by DNA methylation specific PCR, bisulphite modification of DNA and ChIP analyses following PCR respectively.', 'Ectopic expression of CAV1 by epigenetic modulators inhibits colon cancer cell growth. CAV1 promoter DNA remains unmethylated before and after treatment with epigenetic modulators, which confirmed that DNA methylation is not the regulator of CAV1 expression in colon cancer. There was enrichment of H3K4me3 and H3K9AcS10P and depletion of H3K9me3 modifications around the CAV1 promoter.'] |
['We tested the hypothesis that a single injection of botulinum toxin not only has local, but also distant effects on muscle function, biochemistry, and pharmacodynamics of atracurium.', 'Botulinum toxin (2.5 U) was injected into the tibialis muscle of anesthetized rats (n = 26). The contralateral side with no injection served to study distant effects. Control animals (n = 25) received a saline injection. Neuromuscular function, pharmacology, and expression of acetylcholine receptors (nAChRs) were evaluated in the tibialis at 0, 4, and 16 days after injection and in comparison with saline- injected controls.', 'On day 4, botulinum toxin caused complete paralysis of the tibialis, while its contralateral side showed a decrease in absolute twitch tension (1.8 N [1.6; 1.9] vs 3.0 N [2.8; 3.1], Newton, P < 0.05). On day 16, muscle weakness was only present on the toxin-injected side where absolute twitch tension was decreased (0.6 N [0.6, 0.7] vs 3.4 N [3.1, 3.7], P < 0.05). Tibialis mass was decreased on the toxin-injected side at day 4 (1.46 mg/g [1.43, 1.48] vs 1.74 mg/g [1.72; 1.75], P < 0.05) and on day 16 (0.78 mg/g [0.76, 0.79] vs 1.73 mg/g [1.69; 1.77], P < 0.05). Effects distant from the site of injection were seen on day 16, when muscle atrophy was also present in the adjacent gastrocnemius and soleus muscles. Normalized to tibialis mass, specific twitch tension (tension/g muscle) was reduced on the contralateral side at day 4 and on the toxin-injected side at day 16 in relation to saline controls. At day 16, an increased sensitivity to atracurium was seen on the toxin-injected side, evidenced as a decreased ED(50) (0.23 mg/kg [0.13, 0.33] vs 0.72 mg/kg [0.63, 0.82], P < 0.05) and a lower infusion rate (38 μL/kg/min [32, 43] vs135 μL/kg/min [126, 144], P < 0.05), together with a reduced plasma concentration requirement of atracurium (0.5 μg/mL [0.4, 0.7] vs 4.5 μg/mL [3.8, 5.2], P < 0.05) to achieve a steady state 50% reduction in baseline (absolute) twitch tension. ED(50) of atracurium was also decreased on the contralateral side at day 16 in relation to saline controls. The nAChRs in the tibialis were increased on the toxin-injected side to 123 fmol/mg [115, 131] vs 28 fmol/mg [25, 29] (P < 0.05) in time-matched saline-injected controls at day 4 and to 378 [341, 413] vs 27 fmol/mg [25, 29] (P < 0.05) at day 16.'] |
['Paclitaxel (Taxol) is an effective agent against a broad range of human cancers. Studies on the metabolism and disposition of paclitaxel have shown that it is primarily eliminated via hepatic metabolism by P450 enzymes (2C8 and 3A4) to essentially inactive metabolites, and that biliary and gut transport by P-glycoprotein (PGP) as well as urinary elimination of the parent compound play relatively minor roles. Recent studies in vitro have shown that paclitaxel treatment increases the level of CYP2C8 and CYP3A4 in human hepatocytes as well as PGP in colon tumor cells. The data suggest that previous paclitaxel exposure may influence metabolism and elimination of subsequent doses. Further, since weekly paclitaxel dose schedules are becoming more common as opposed to the original every 21-day dosing, the likelihood of enzyme induction from previous doses impacting that from subsequent doses is increased.', 'To study the potential for such sequence-dependent alterations in paclitaxel pharmacokinetics, we carried out pharmacokinetic studies in mouse plasma and tissues following day 1 and days 1 and 5 dosing at 20 mg/kg. Paclitaxel concentrations were determined by a sensitive LC/MS/MS assay out to 16 h post-dosing in plasma, liver, kidney, gut and heart. The effect of paclitaxel treatment on hepatic expression of PGP and P450 isoforms (CYP2C and CYP3A) was determined to elucidate the mechanism by which paclitaxel disposition is altered by previous drug exposure.', 'Pharmacokinetic analysis of the data showed that plasma and tissue AUC values after treatment on day 5 following a dose on day 1 were between 50% and 74% of those determined following a single dose on day 1. The terminal elimination half-life was not different. Activity and protein levels for CYP2C in liver were elevated at 24 and 96 h after paclitaxel dosing. Cremophor EL, a carrier solvent for paclitaxel, also caused elevated CYP2C activity. Neither CYP3A nor PGP levels in liver were altered by paclitaxel or Cremophor EL treatment at the 24-h and 96-h time points. The levels of 6alpha-OH-paclitaxel in feces were increased on day 5 as opposed to day 1 while paclitaxel levels in feces were unchanged.'] |
['Hypocalcemia is the most common complication after total thyroidectomy. Some patients need to stay in the hospital for monitoring of hypocalcemic symptoms and serum calcium levels for several days. We investigated the efficacy and safety of using early postoperative parathyroid hormone (PTH) results for early discharge after thyroidectomy.', 'A retrospective cohort study of 2 sequential groups of patients undergoing total thyroidectomy between January 2010 and March 2013 was undertaken. Patients were divided into 2 groups. In Group 1 (before June 2011), patients had daily monitoring of serum calcium level and hypocalcemic symptoms. They were discharged when calcium level was static and asymptomatic. Postoperative PTH was not utilized for discharge plan. In Group 2 (after June 2011), postoperative PTH and calcium level on day 1 were utilized to dictate subsequent management and discharge plan.', 'Of the 107 patients reviewed, 54 (50.5%) were in Group 1 and 53 (49.5%) were in Group 2. A total of 51 (47.7%) patients developed hypocalcemia. The two groups were comparable in demographic data, early postoperative PTH value, rate of hypocalcemia, the need for oral calcium and vitamin D supplements and rate of permanent hypoparathyroidism. Fewer patients in Group 2 experienced hypocalcemic symptoms, p=0.005. None of the patients in Group 2 needed intravenous calcium supplement (p=0.003). The median postoperative hospital stay for Group 1 was 4 days and for Group 2 was 1 day (p<0.0001).'] |
['Exercise improves the diagnostic performance of ankle-to-brachial index (ABI) in the detection of exercise-induced arterial endofibrosis (EIAE). Pressure values for all four limbs are required to calculate ABI, but rapid systemic pressure changes occur during the recovery period from exercise. We checked whether after exercise, ABI calculated from simultaneous measurements was better than from consecutive measurements for differentiating athletes with EIAE from normal athletes.', 'We studied 42 normal athletes and 42 athletes suffering from unilateral pain caused by histologically proven EIAE. Bilateral brachial and ankle (ASBP) systolic blood pressure levels were simultaneously measured in the supine position at rest and every minute during the first 4 min of the recovery from incremental maximal exercise. Using receiver operating characteristics curves (ROC), we compared the diagnostic performance of single-leg ASBP and ABI values and between-leg ASBP (DeltaASBP) and ABI (DeltaABI) differences, calculated from simultaneous (simu) versus consecutive (cons) measurements, to discriminate athletes with EIAE from normal athletes.', 'For single-leg postexercise values, ROC curve area was significantly higher for ABIsimu compared with ASBPsimu (P < 0.05, r = 0.91) and ASBPrand (P < 0.05, r = 0.68). Areas (+/- SE of area) of the ROC curves for postexercise Delta ASBPsimu and Delta ABIsimu were 0.97 +/- 0.01 and 0.97 +/- 0.02, respectively, and were higher than areas for postexercise Delta ASBP and Delta ABI calculated from consecutive and random measurements (P < 0.01). Accuracy for postexercise Delta ASBPsimu and Delta ABIsimu in discriminating EIAE from normal athletes was 93% [95% CI; 85-97], with a cutoff point of 22 mm Hg and 0.10, respectively.'] |
['To evaluate the indications for and the outcomes from distal pancreatectomy.', "Retrospective chart review of 171 patients who underwent distal pancreatectomy at Brigham and Women's Hospital between January 1996 and August 2005.", 'Nearly one-third of distal pancreatectomies were performed as part of an en bloc resection for a contiguous or metastatic tumor. Fifty-six percent of the patients underwent a standard distal pancreatectomy +/- splenectomy (group 1), whereas 44% of distal pancreatic resections included additional organs or contiguous intraperitoneal or retroperitoneal tumor (group 2). The overall post-operative complication rate was 37%; the most common complication was pancreatic duct leak (23%). When compared to patients undergoing standard distal pancreatectomy, those with a more extensive resection including multiple viscera and/or metastatic or contiguous tumor resection had no significant difference in overall complication rate (35% v. 39%, p = 0.75), leak rate (25% v. 20%, p = 0.47), new-onset insulin-dependent diabetes mellitus (3% v. 4%, p = 1.0), and mortality (2% v. 4%, p = 0.656).'] |
['Array-based comparative genomic hybridization (aCGH) is a new technique for detecting submicroscopic deletions and duplications, and can overcome many of the limitations associated with classic cytogenetic analysis. However, its clinical use in spontaneous abortion needs comprehensive evaluation. We used aCGH to investigate chromosomal imbalances in 100 spontaneous abortions and compared the results with G-banding karyotyping and fluorescence in situ hybridization (FISH). Inconsistent results were verified by quantitative fluorescence PCR.', "Abnormalities were detected in 61 cases. aCGH achieved the highest detection rate (93.4%, 57/61) compared with traditional karyotyping (77%, 47/61) and FISH analysis (68.9%, 42/61). aCGH identified all chromosome abnormalities reported by traditional karyotyping and interphase FISH analysis, with the exception of four triploids. It also detected three additional aneuploidy cases in 37 specimens with 'normal' karyotypes, one mosaicism and 10 abnormalities in 14 specimens that failed to grow in vitro."] |
['Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease and impaired left ventricular (LV) function, yet the impact of NAFLD on right ventricular (RV) function remains unclear. We investigate the RV functional properties in patients with NAFLD.', 'Ninety consecutive patients with the diagnosis of biopsy-proven NAFLD and 45 age- and sex-matched controls were included. All patients underwent an echocardiographic examination. RV function was evaluated by two-dimensional (2D) speckle-tracking echocardiography (STE).', 'Mean fibrosis stage and nonalcoholic steatohepatitis (NASH) scores were 1.3\xa0±\xa01.1 and 5.2\xa0±\xa01.6, respectively. NAFLD patients displayed decreased RV function compared to controls. NAFLD patients with liver fibrosis (67 patients) had significantly lower RV function assessed by GLS (global longitudinal strain) compared to patients without liver fibrosis (18.9\xa0±\xa03.4% vs. 21.6\xa0±\xa02.3%, P\xa0<\xa00.001). NASH score ≥5 was associated with lower RV-GLS (18.9\xa0±\xa03.1% vs. 21.0\xa0±\xa03.4%, P\xa0=\xa00.006). NASH score inversely correlated with RV-GLS (r\xa0=\xa0-0.370, P\xa0<\xa00.001) such as patients with impaired RV-GLS (<19%) showed significantly higher NASH score compared to normal RV-GLS group (5.8\xa0±\xa01.4 vs. 4.8\xa0±\xa01.7, P\xa0=\xa00.009). Logistic regression analysis revealed that NASH score was an independent predictor of impaired RV function in patients with NAFLD.'] |
['Cow milk protein allergy occurs in 2% to 6% of infants population. Goat milk has been used as an alternative to cow milk, but there is probably some cross-reactivity between the milks. Little is known about the allergenicity of goat milk per se. The aim of this study is to compare cow and goat milk allergenicity in a mouse atopy model.', 'Balb/C mice were intragastrically sensitized to cow or goat milk by five doses administrated weekly. Six weeks after the first dose mice were killed, sera were collected and spleens removed for analysis.', 'The number of mice with diarrhea was significantly higher in the cow milk-sensitized group than in the goat milk-sensitized group. Serum cow milk-specific immunoglobulin G1 and histamine levels were also significantly higher in cow milk-sensitized mice. Cytokine production by spleen derived T cells showed a Th2 response with high levels of interleukin-4 production and low levels of interferon-gamma in cow milk-sensitized mice. In addition, goat milk induced a lower lymphocyte sensitization as a result of a significant decrease in the specific proliferation ratio of these cells.'] |
['Proprotein convertase subtilisin kexin/type 9 (PCSK9) is an inhibitor of the low density (LDL) lipoprotein receptor. Plasma PCSK9 is increased by fenofibrate and statins. Here, we determined how standard dose of statin and combined therapy with fenofibrate modulate PCSK9.', 'Randomized, open-label cross-over study investigating the effect of fenofibrate (160 mg), atorvastatin (10 mg), and combination of both in patients with type 2 diabetes mellitus and atherogenic dyslipidemia. After the single administration of atorvastatin and fenofibrate for 6 weeks, patients received both for another 6 weeks. PCSK9, lipids and lipoproteins levels were determined at day 1, weeks 6, 9 and 12.', 'Upon 6 weeks of treatment, atorvastatin decreased LDL-cholesterol by 30% (p<0.001) and fenofibrate decreased triglyceride level by 31% (p<0.01) and increased HDL-cholesterol by 13% (p<0.05). Combination did not show further benefit. Atorvastatin increased PCSK9 by 24% at day 1 and by 14% at week 6 (p < or = 0.01). Fenofibrate increased PCSK9 by 26% at week 6 (p < or = 0.01), but had no effect at day 1. Three weeks of combination therapy increased PCSK9 by 42%, 6 weeks by 19% (p < or = 0.01). PCSK9 changes were not different between treatments over 6-week periods.'] |
['Dyslipidaemia, insulin resistance, metabolic syndrome and HIV/HAART-associated lipodystrophy syndrome (HALS) are common comorbidities in HIV-1-infected patients, which may increase cardiovascular risk. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone with effects on metabolism and phosphate homeostasis. The aim of this study was to determine the relationship between FGF23 levels, metabolic alterations, fat distribution and cardiovascular risk.', 'This was a cross-sectional study. Serum FGF23 levels were analysed in 152 patients and 34 healthy control individuals. Patients belonged to three groups: HIV-1-infected, antiretroviral-treated patients who have developed HALS (n\u200a=\u200a60); HIV-1-infected, antiretroviral-treated patients without HALS (n\u200a=\u200a43); and untreated (naive) HIV-1-infected patients (n\u200a=\u200a49). Serum FGF23 levels were compared with lipid and glucose homeostasis parameters, fat distribution and cardiovascular risk.', 'Serum FGF23 levels were increased in HIV-1-infected patients, but the increase was most marked in those with HALS. FGF23 levels showed a strong positive correlation with age, indicators of dyslipidaemia (LDL cholesterol, polyunsaturated fatty acids and monounsaturated fatty acids), HALS parameters (trunk/appendicular fat ratio), insulin resistance (fasting insulin\xa0and homeostasis model assessment of insulin resistance) and C-reactive protein. FGF23 levels correlated with cardiovascular risk but correlation was lost after age adjustment.'] |
['Epidural anesthesia potentiates sedative drug effects and decreases minimum alveolar concentration (MAC). The authors hypothesized that epidural anesthesia also decreases the general anesthetic requirements for adequate depth of anesthesia as measured by Bispectral Index (BIS).', 'After premedication with 0.02 mg/kg midazolam and 1 microg/kg fentanyl, 30 patients aged 20-65 yr were randomized in a double-blinded fashion to receive general anesthesia with either intravenous saline placebo or intravenous lidocaine control (1-mg/kg bolus dose; 25 microg x kg(-1) x min(-1)). A matched group was prospectively assigned to receive epidural lidocaine (15 ml; 2%) with intravenous saline placebo. All patients received 4 mg/kg thiopental and 1 mg/kg rocuronium for tracheal intubation. After 10 min of a predetermined end-tidal sevoflurane concentration, BIS was measured. The ED50 of sevoflurane for each group was determined by up-down methodology based on BIS less than 50 (MAC(BIS50)). Plasma lidocaine concentrations were measured.', 'The MAC(BIS50) of sevoflurane (0.59% end tidal) was significantly decreased with lidocaine epidural anesthesia compared with general anesthesia alone (0.92%) or with intravenous lidocaine (1%; P < 0.0001). Plasma lidocaine concentrations in the intravenous lidocaine group (1.9 microg/ml) were similar to those in the epidural lidocaine group (2.0 microg/ml).'] |
['Depression is known to be a risk factor for cardiovascular diseases but the underlying mechanisms remain unclear. Since recent preclinical evidence suggests that endogenous agonists of cannabinoid receptors (endocannabinoids) are involved in both cardiovascular function and depression, we asked whether endocannabinoids correlated with either in humans.', 'Resting blood pressure and serum content of endocannabinoids in ambulatory, medication-free, female volunteers with depression (n = 28) and their age- and ethnicity-matched controls (n = 27) were measured. In females with depression, both diastolic and mean arterial blood pressures were positively correlated with serum contents of the endocannabinoids, N-arachidonylethanolamine (anandamide) and 2-arachidonoylglycerol. There was no correlation between blood pressure and endocannabinoids in control subjects. Furthermore, depressed women had significantly higher systolic blood pressure than control subjects. A larger body mass index was also found in depressed women, however, it was not significantly correlated with serum endocannabinoid contents.'] |
['Hyperglycemia generates reactive oxygen species and prevents isoflurane-induced preconditioning. The authors tested the hypothesis that scavenging reactive oxygen species with N-acetylcysteine will restore protection against myocardial infarction produced by isoflurane in vivo.', 'Barbiturate-anesthetized dogs (n = 45) were instrumented for measurement of systemic hemodynamics. Myocardial infarct size and coronary collateral blood flow were measured with triphenyltetrazolium staining and radioactive microspheres, respectively. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Dogs were randomly assigned to receive an infusion of 0.9% saline or 15% dextrose in water to increase blood glucose concentrations to 600 mg/dl (hyperglycemia) in the absence or presence of isoflurane (1.0 minimum alveolar concentration) with or without pretreatment with N-acetylcysteine (150 mg/kg i.v.) in six experimental groups. Isoflurane was discontinued, and blood glucose concentrations were allowed to return to baseline values before left anterior descending coronary artery occlusion.', 'Myocardial infarct size was 27 +/- 2% (n = 8) of the left ventricular area at risk in control experiments. Isoflurane significantly (P < 0.05) decreased infarct size (13 +/- 2%; n = 7). Hyperglycemia alone did not alter infarct size (29 +/- 3%; n = 7) but abolished the protective effect of isoflurane (25 +/- 2%; n = 8). N-Acetylcysteine alone did not affect infarct size (28 +/- 2%; n = 8) but restored isoflurane-induced cardioprotection during hyperglycemia (10 +/- 1%; n = 7).'] |
['\u2002 Hepatitis C virus (HCV) proteins can activate the PI3K/Akt pathway which is involved in multiple cellular functions such as inflammatory cell activation and liver fibrosis. The aim of the present study was to elucidate the correlation between Akt expression and liver fibrosis staging in chronic hepatitis C (CHC) patients.', '\u2002 Paraffin-embedded liver sections from 133 consecutive treatment-naïve CHC patients were recruited. The expression features of Akt were analyzed using immunohistochemical methods and the results were compared with histological, virological and biochemical profiles.', '\u2002 The 73 patients with high Akt expression carried higher histological activity index scores (6.52\u2003±\u20032.5 vs 5.62\u2003±\u20032.4, P\u2003=\u20030.04) and advanced fibrosis (72.7% vs 26.3%, P\u2003<\u20030.01) than other 60 patients with low Akt expression. The high Akt expression showed a significant incremental trend dependent on fibrosis stages, from 33.3% of F0 to 85.7% of F4 (P\u2003=\u20030.005). Akt expression was not correlated with degrees of steatosis and virological features of HCV infection, such as viral load and genotypes. Multivariate logistic regression analysis showed advanced fibrosis was the most significant factor associated with high Akt expression (odds ratio\u2003=\u20033.16).'] |
['Black American heart transplant recipients receiving cyclosporine-based primary immunoprophylaxis suffer higher rates of allograft rejection with hemodynamic compromise, infections, and posttransplant coronary artery disease. We examined the hypothesis that a combination of tacrolimus and mycophenolate mofetil "resurrects" clinical outcome of black Americans to those seen in white heart transplant recipients.', 'Sixty-three adult primary heart transplant recipients were included in this study. Twenty black American and 21 white patients who received tacrolimus-based primary immunoprophylaxis were enrolled in this prospective, observational parallel cohort investigation. A separate group of 22 black American patients were randomly allocated to receive cyclosporine-microemulsion-based primary prophylaxis and served as the control population for assessing outcomes in the black American group. Adjunctive immunosuppression included mycophenolate mofetil and corticosteroids. The primary end-point was the freedom from allograft rejection requiring treatment at 1 year. Secondary end-points included rejection with hemodynamic compromise, and patient or graft survival. Adverse events evaluated included development of infections requiring hospitalization and nonimmunological outcomes including hyperlipidemia, hypertension, and diabetes mellitus (new onset or worsened).', 'Tacrolimus-treated black American patients had greater freedom from allograft rejection requiring treatment at 1 year than those treated with cyclosporine (64% vs. 37%, P=0.01). No differences were noted between tacrolimus-treated black Americans and whites in the primary end point (64% and 67% respectively, P=nonsignificant [NS]). Tacrolimus-based immunosuppression was associated with better 1-year survival in black Americans compared with cyclosporine (95% vs. 73%, P=0.04), and this end point was similar to that achieved in tacrolimus-treated white heart transplant recipients (95%). No differences in infection rates were noted among either group. Cyclosporine-treated black Americans suffered more hyperlipidemia and worse hypertension than tacrolimus-treated patients.'] |
['To explore the association between previous severe HIV disease, defined as past Centers for Disease Control and Prevention class C diagnosis, and neurocognitive and psychiatric outcomes in long-term survivors of perinatally acquired HIV.', 'A retrospective cohort study of perinatally HIV-infected adolescents receiving outpatient care at a single site.', 'Comparisons were made between those with and without class C diagnoses.', 'Eighty-one patients formed the study group, 47% were females and 72% were African-American. Median patient age was 15 years (interquartile range 13-17). Of the study group, 47% had a past class C diagnosis. The median age at class C diagnosis was 3.1 years (interquartile range 0.9-8.1). There were no significant differences between the groups with respect to most recent CD4(+) cell percentage or plasma viral RNA level. Class C patients were more likely to have a history of psychiatric diagnosis [odds ratio 2.6; 95% confidence interval (CI) 1.1-6.3], psychiatric hospitalization (odds ratio 4.8; 95% CI 1.2-17.4), or learning disability (odds ratio 4.5; 95% CI 1.7-11.4). There was a significant difference in full-scale intelligence quotient between the groups (adjusted linear regression coefficient -11.7; 95% CI -17.9 to 5.5). After adjusting for age at antiretroviral therapy initiation, the associations between class C diagnosis and lower full-scale intelligence quotient, learning disorders, and psychiatric diagnoses remained significant.'] |
['This study seeks to examine whether existing study-level data meta-analysis approaches can be used to produce unbiased and precise effect estimates relative to meta-analyses conducted using patient-level data, where a recurrent event is the outcome of interest.', 'Data from two studies focusing on the prevention of falls in the hospital setting (N=1,838 total) was divided into the three hospital sites from which data were collected. Outcome data were considered as recurrent event survival data, single event survival data, count data, rate data, and binary data. A range of analysis approaches were considered.', 'Andersen-Gill, negative binomial, bootstrap resampling, and modified relative risk analysis approaches produced congruous point estimates of effect, whereas modified relative risk analysis produced considerably smaller standard errors. Pooled effect point estimates derived from these approaches were not consistent when using study-level data as opposed to patient-level data, and 95% confidence intervals were excessively wide when between-study heterogeneity was present.'] |
['To compare the proliferation of endothelial, epithelial, and stromal cells in the endometrium of women with endometriosis and normal controls.', 'Proliferating cells were identified using the monoclonal antibody antiproliferating cell nuclear antigen. A second antibody (CD34) was used to identify endothelial cells (ECs).', 'University Department of Obstetrics and Gynaecology.', 'Women with laparoscopically proven endometriosis, n = 30. Controls were women with a normal pelvis at laparoscopy performed for tubal sterilization or for infertility due to a male factor, n = 27.', 'Endothelial cells: proliferative index. Epithelial and stromal cells: semi-quantitative immunostaining score.', 'The mean EC proliferative index was significantly greater in those with endometriosis compared with controls. This difference was most marked during the proliferative phase of the menstrual cycle. Proliferative phase epithelial and stromal cells demonstrated significantly higher immunostaining scores in endometriosis patients than in controls.'] |
['The tibial nerve provides the majority of sensation to the foot. Although multiple techniques have been described, there exists little evidence-based medicine evaluating different techniques for blocking the tibial nerve at the ankle. We hypothesized that an ultrasound (US)-guided tibial nerve block at the ankle would prove more successful than a conventional approach based on surface landmarks.', "Eighteen healthy volunteers were prospectively randomized into this controlled and blinded study. Each subject was placed prone, and one ankle was randomly assigned to receive either an US-guided tibial nerve block (group US) or a traditional landmark-based tibial nerve block (group LM). The subject's other ankle then received the alternate approach. All blocks were performed with 5 mL of 3% chloroprocaine. We evaluated sensory and motor blocks. A successful block was defined as complete loss of sensation to both ice and pinprick at 5 cutaneous sites. Secondary outcome variables included performance times, number of needle passes, participant satisfaction, and presence of any complications.", 'At 30 mins, the block was complete in 72% of participants in group US as compared with 22% in group LM. At all times, the proportion of complete blocks was higher in group US. Ultrasound-guided blocks took longer on average to perform than traditional blocks (159 vs 79 secs; P < 0.001). There were more needle redirects in group US, with 8 subjects requiring 3 or more redirects versus none in group LM. Subjects preferred the US block 78% of the time (95% confidence interval, 52%-95%).'] |
['Chromium allergy has traditionally been caused by occupational skin contact with cement. In 1983, Danish legislation made the addition of ferrous sulphate compulsory in cement to reduce the water-soluble chromium content to not more than 2 ppm. An effect from this intervention has previously been demonstrated among Danish construction workers.', 'To investigate the development of chromium allergy among patients with dermatitis tested between 1985 and 2007 in Denmark. Furthermore, to determine causative exposures in patients with chromium allergy.', 'A retrospective analysis of patch test data was performed (n = 16,228) and charts from patients with chromium allergy were reviewed. Comparisons were made using a chi(2) test. Logistic regression analyses were used to test for associations.', 'The prevalence of chromium allergy decreased significantly from 3.6% in 1985 to 1% in 1995 (P(trend) < 0.001) but increased to 3.3% in 2007 (P(trend) < 0.001). The frequency of clinically relevant cement exposure decreased significantly among patients with chromium allergy from 12.7% in 1989-1994 to 3.0% (P < 0.01) in 1995-2007, whereas the frequency of relevant leather exposure increased significantly from 24.1% during 1989-1994 to 45.5% during 1995-2007 (P < 0.02).'] |
['Premenopausal migraines frequently are associated with fluctuations of estrogen levels. Both, migraine and combined hormonal contraceptives (CHC) increase the risk of vascular events. Therefore progestagen-only contraceptives (POC) are a safer alternative. A previous short-term study demonstrated a positive impact of the oral POC desogestrel on migraine frequency. To study the effect of the POC desogestrel 75 μg on migraine frequency, intensity, use of acute medication and quality of life in a clinical setting over the period of 180 days.', "Patients' charts were screened for women with migraine, who had decided to use desogestrel for contraception. Charts were included, if routinely conducted headache diaries were complete for 90 days before treatment (baseline) and over a treatment period of 180 days. We also report about starters who stopped treatment early, because of adverse events. Baseline data (day 1-90 before treatment) were compared with first and second treatment period (treatment days 1-90 and days 91-180). Quality of life was evaluated using MIDAS questionnaires.", 'Days with migraine (5.8 vs 3.6), with any kind of headache (9.4 vs 6.6), headache intensity (15.7 vs 10.7), days with severe headache (5.4 vs 2.4) and use of triptans (12.3 vs7.8) were significantly reduced after 180 days. MIDAS score and grade improved significantly.'] |
['Endothelin-1 (ET-1) has potent vasoconstrictor and hypertrophic actions. Pharmacological antagonists of endothelin receptors attenuate cardiac hypertrophy, have been approved for treatment of pulmonary hypertension, and are under investigation for treatment of heart failure. To investigate the role of ET-1 in the heart, we created mice with cardiomyocyte deletion of ET-1.', 'Mice with cardiomyocyte-specific deletion of ET-1 are phenotypically normal when young. Remarkably, as the mice age or when young animals are subjected to aortic banding, they develop an unexpected phenotype of progressive systolic dysfunction and cardiac dilation. Echocardiography, necropsy, histology, and molecular phenotype confirm a dilated cardiomyopathy. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling analysis reveals greater abundance of apoptotic nuclei in the ET-1-deficient hearts. Transcriptional and Western analyses suggest enhanced tumor necrosis factor (TNF)-mediated apoptosis with increases in caspase-8 activity. These ET-1-deficient hearts also have diminished nuclear factor (NF)-kappaB activity, resulting in diminution of downstream inhibitors of TNF signaling.'] |
['The glucokinase regulatory protein (GCKR) regulates the activity of the glucokinase (GCK), which plays a key role in glucose homeostasis. Genetic variants in GCK have been associated with diabetes and gestational diabetes (GDM). Due to the relationship between GCKRP and GCK, polymorphisms in GCKR are also candidates for genetic association with GDM. The aim of this study was to evaluate the association between the GCKR rs780094 polymorphism and GDM in a Brazilian population.', '252 unrelated Euro-Brazilian pregnant women were classified as control (healthy pregnant women, n = 125) and GDM (pregnant women with GDM, n = 127) age-matched groups. Clinical and anthropometric data were obtained from all subjects. The GCKR rs780094 polymorphism was genotyped using fluorescent probes (TaqMan', 'Both groups were in Hardy-Weinberg equilibrium. The GCKR rs780094 polymorphism was associated with GDM in codominant and dominant models (P = 0.022 and P = 0.010, respectively). The minor allele (T) frequency for the control group in the study was 38.4% (95% CI: 32-44%), similar to frequencies reported for other Caucasian populations.'] |
['Clinical manifestations of autoimmune hepatitis (AIH) range from mild chronic to acute, sometimes fulminant hepatitis. However, it is unknown how the progression to fatal hepatitis occurs. We developed a mouse model of fatal AIH by inducing a concurrent loss of forkhead box P3(+) regulatory T cells and programmed cell death-1 (PD-1)-mediated signaling. In this model, dysregulated follicular helper T cells in the spleen are responsible for the induction, and the C-C chemokine receptor 6/C-C chemokine ligand 20 axis is crucial for the migration of these T cells into the liver. Using this fatal AIH model, we aimed to clarify key molecules triggering fatal AIH progression. During progression, T-bet together with interferon (IFN)-γ and C-X-C chemokine receptor (CXCR)3 were highly expressed in the inflamed liver, suggesting helper T (Th)1-type inflammation. T cells that dominantly expanded in the spleen and the inflamed liver were CXCR3-expressing CD8(+) T cells; depletion of these CD8(+) T cells suppressed AIH progression. Expression of one CXCR3 ligand, chemokine (C-X-C motif) ligand (CXCL)9, was elevated in the liver. CXCL9-expressing macrophages/Kupffer cells were colocalized with infiltrating T cells, and in vivo administration of anti-CXCL9 suppressed AIH progression. In addition, serum levels of interleukin (IL)-18, but not IL-1β, were elevated during progression, and dendritic cells in the spleen and liver highly produced IL-18. In vivo administration of anti-IL-18R suppressed the increase of splenic CXCR3(+) T cells and the progression to fatal AIH. Moreover, tumor necrosis factor alpha, but not IFN-γ, was involved in up-regulating CXCL9 in the liver and for increased serum levels of IL-18.'] |
["In patients with hematologic malignancies who receive stem-cell transplantation, donors' T cells can recognize minor histocompatibility antigens on recipient cells and generate an objective response against the tumor. However, a major side effect of such therapy is graft-versus-host disease (GVHD). The purpose of this study was to characterize distinct T-cell clones that were frequently and exclusively involved in GVHD or graft-versus-tumor (GVT) effects.", 'We hypothesized that distinct GVHD-associated T-cell clones can be identified during the disease progression. To test this, we conducted comparative analysis of T-cell receptor (TCR) Vβs in donor-recipient pairs of patients with GVHD versus those with GVHD-free and relapse-free survival using quantitative reverse-transcriptase polymerase chain reaction and spectratyping analyses.', 'We identified three sets of T-cell clones that were either frequently involved in GVHD (TCR Vβ4, 11, and 23) or GVT effect (TCR Vβ9, 16, and 20), or were increased at the time of GVHD and GVT effects in a patient-specific manner (TCR Vβ2, 3, 7, 12, 15, and 17). Spectratyping analysis showed restricted clonality of the identified TCR Vβs. Polymerase chain reaction analysis also confirmed the presence of GVHD-associated T-cell clones at the site of the disease.'] |
['Activation of SIRT1 deacetylase prevents retinal ganglion cell (RGC) loss in experimental optic neuritis, an inflammatory optic neuropathy. While mechanisms of this effect are not known, evidence suggests it involves reduction of oxidative stress. We hypothesized that SIRT1 reduces RGC loss due to oxidative stress in noninflammatory optic neuropathies, and examined effects following traumatic injury.', 'Optic nerve crush injury was induced in wild-type C57BL/6 mice, mice overexpressing SIRT1, and mice with conditional deletion of SIRT1 in neurons. Wild-type mice were treated daily with vehicle or 250 mg/kg resveratrol, a naturally occurring polyphenol that activates SIRT1. RGC function was assessed by pupillometry and optokinetic responses (OKR), and RGC survival was measured. Superoxide levels were measured to assess oxidative stress.', 'Significant decreases in pupillary light responses, OKR and RGC survival occurred 1 week after optic nerve crush, with progressive worsening at 2 to 4 weeks. Resveratrol treatment and SIRT1 overexpression delayed RGC loss and loss of pupillary light responses following optic nerve crush, although no change in RGC loss occurred in neuronal SIRT1-deficient mice. A significant accumulation of superoxide was detected in wild-type optic nerves following crush, and was reduced in mice overexpressing SIRT1 or treated with resveratrol.'] |
['To develop a qualitative exposure classification of employees in Norwegian smelters and to investigate the relationship between respiratory symptoms and occupational exposure using this classification.', 'The 3,924 participants completed a standardised questionnaire including questions of respiratory symptoms, familial asthma, allergy, doctor-diagnosed asthma, smoking habits, previous exposure and occupation. The employees were classified according to their current job function: (1) line operators were employed full time on the production line, (2) non-exposed employees did not work in production, (3) the remaining employees were classified as non-line operators. The association between the prevalence of respiratory symptoms and job category was examined using multivariate logistic regression.', 'The mean age of the participants was 38.6 years (standard deviation 9.2 years), 88.5% were males. The odds ratios (OR) (95% confidence intervals in parenthesis) for dyspnoea, cough and phlegm regarding previous exposure compared with no previous exposure were 1.4 (1.1-1.7), 1.4 (1.2-1.8) and 1.3 (1.0-1.7), respectively. The OR in line operators compared with non-exposed employees was 1.2 (0.9-1.7) for dyspnoea, 1.3 (1.0-1.8) for cough and 1.9 (1.4-2.7) for phlegm. The OR for respiratory symptoms was higher in relation to previous exposure than current job function except for phlegm.'] |
['Although both colorectal neoplasms and atherosclerosis may be induced by visceral fat accumulation, no association between these factors has yet been elucidated.', 'Among Japanese participants in our colonoscopic screening and annual surveillance programs, asymptomatic subjects were investigated. Visceral fat area was measured by computed tomography, and the ankle-brachial index and pulse-wave velocity (markers of systemic atherosclerosis) were also estimated. Colorectal findings during screening were investigated in association with these parameters.', 'Nine hundred and seven subjects (males: 71.9%; mean age: 57.3±8.7 years) were enrolled. Colorectal adenomas were identified during colorectal screening of 407 subjects (44.9%). The prevalence of all colorectal adenoma and advanced neoplasia increased with an elevated pulse-wave velocity from 32.2% (advanced neoplasia, 2.6) to 62.1% (8.4%) in higher quartiles (p<0.001 and p=0.003). The risk of advanced neoplasia was higher in subjects with an abnormal ankle-brachial index (33% vs. 4.6%, p<0.001). Upon multivariate analysis, visceral fat area and pulse-wave velocity were associated with all adenoma, and the ankle-brachial index with advanced neoplasia.'] |
['Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood.', 'Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response.', 'Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1β in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone.'] |
['The Atreus 2C+ system automates whole blood (WB) processing into a red cell concentrate, plasma and buffy coat (BC) suitable for platelet concentrate (PC) manufacture. This study compared the quality of PC made from BC using the Atreus, with those made by a manual method.', 'WB was collected into Atreus disposables or standard bottom and top processing packs and held without active cooling for 26 h at 22 +/- 2 degrees C before processing, either with the Atreus, or using a centrifuge and press. BC were rested for 3 h and then 4 BC were pooled with one unit of plasma, mixed, centrifuged and pressed to make a pooled PC. The PC were analysed for quality markers to day 9 of storage.', 'Platelet quality was good in both Atreus 2C+ derived PC and control units throughout storage. Metabolic markers (pH, ATP and HSR) and activation markers (CD62P, sCD62P, annexin V binding, microparticles, GP IIb/IIIa) did not differ between the Atreus and control units. Atreus-derived PC had significantly lower platelet yields (302 +/- 59 x 10(9) platelets/unit; mean +/- standard deviation, n = 8) than control PC (411 +/- 76 x 10(9) platelets/unit; P < 0.01), but met the UK guidelines for platelet yield.'] |
['To determine bone mass using quantitative phalangeal bone ultrasound in young coeliac patients after a long-term gluten-free diet.', 'A total of 99 patients with coeliac disease (CD) (52 girls, mean age 15.5 +/- 9.7 years; 47 boys, mean age 14.4 +/- 8.4 years) and 44 healthy subjects matched for age, weight and height (26 girls, mean age 18.4 +/- 9.9 years; 18 boys, mean age 16.3 +/- 11.2 years) were included in the study.', 'Bone status was assessed using an ultrasound device that measures amplitude-dependent speed of sound (Ad-SoS) in metres per second. Measurements were made on the phalanges (II-V) of the non-dominant hand, and an average value was computed. Nutrient intake was assessed using a 7-day record.', 'Analysis of variance (ANOVA) and the unpaired t-test showed that the intake of phosphates (P < 0.05), proteins, fat and carbohydrates (P < 0.005 in all) was higher in patients than in controls. No significant difference in Ad-SoS was found between patients and controls (95% CI -10.9 to 60.6) in the overall group, in girls or boys, or in patients following a gluten-free diet strictly or partially. In the patients, only age (beta 4.01, 95% CI 1.84-6.16, P < 0.0005) and weight (beta 2.62, 95% CI 1.53-3.70, P < 0.0001) showed a significant positive relation with Ad-SoS.'] |
['This study investigated whether endothelial dysfunction occurs in mesenteric arteries of apoE-deficient mice and determined the role of endothelin (ET)-1, which is increased in human atherosclerosis, using an orally active endothelin ET(A) receptor antagonist.', 'ApoE-deficient and C57BL/6J control mice were fed for 30 weeks with normal chow or high-fat Western-type diet alone or in combination with darusentan (LU135252; 50 mg/kg/day). Vasomotor reactivity of isolated small mesenteric arteries (I.D. 200-250 microm) was studied in vitro under perfused and pressurized conditions.', 'In both mouse strains, about one fourth of the endothelium-dependent relaxant response to acetylcholine was insensitive to inhibition by L-NAME and indomethacin. In mesenteric arteries of apoE-deficient mice on Western-type diet, increased intima-media thickness and levels of endothelin-1 protein were observed. In addition, NO-mediated endothelium-dependent relaxation to acetylcholine was reduced without affecting L-NAME/indomethacin insensitive relaxation and contractions to endothelin-1 and serotonin were enhanced. Treatment with darusentan normalized vascular structure, NO-mediated relaxation to acetylcholine and contractions to endothelin-1 and serotonin without affecting blood pressure or plasma cholesterol levels.'] |
['Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Although ω-3 fatty acids are known to have antiinflammatory effects, their effect against NEC remains unclear.', 'Mother rats fed a soybean-based, docosahexaenoic acid (DHA)- or eicosapentaenoic acid (EPA)-enriched diet from days 7 to 20 of gestation were examined. On day 20, the rat pups were delivered by abdominal incision, their intestines were removed, and messenger RNA was extracted. A rat NEC model was used to confirm the effects of ω-3 fatty acids on the inflamed intestine (n = 20-28). The expression of inflammatory molecules was analyzed by real-time polymerase chain reaction (n = 11-14).', 'The concentrations of DHA and EPA in the intestine were significantly increased in the DHA and EPA groups (P < .01). The expression of the antiinflammatory prostaglandin E2 receptor EP3 was increased in the DHA (P < .05) and EPA groups (P < .01). In the NEC model, the reduced incidence of colitis was confirmed in the DHA and EPA groups. The expression of peroxisome proliferator-activated receptor γ was increased (P < .05), and the inhibitor of nuclear factor-κB α/β decreased in both the DHA (P < .01) and EPA groups (P < .05).'] |
['P-wave dispersion (PWD) is a useful predictor of paroxysmal atrial fibrillation (AF). The effect of cardiac resynchronization therapy (CRT) on PWD and the prognostic implications of the improvement in PWD remain undefined. The aim of the study was to explore the clinical significance of the improvement of PWD after CRT.', 'Electrocardiographic studies were performed before and three months after CRT in 81 patients (57 men and 24 women; age (60.5 ± 11.2) years) with standard CRT indication but no history of AF. A significant improvement of PWD (PWD responder) was defined as a relative decrease ≥ 20% from baseline PWD. The primary endpoints were new-onset AF detected by electrocardiogram (ECG) or CRT.', 'After (30.6 ± 7.5) months of follow-up, PWD responders (n = 43) had a significantly lower incidence of AF than did PWD nonresponders, 12% vs. 29% (P < 0.001). In Cox proportional hazard analysis, PWD responders was the only predictor of lower risk of new-onset AF (HR 0.33, 95% confidence interval 0.12 - 0.96, P = 0.033).'] |
['Chronic high levels of PTH may be associated with up-regulation of proteases and cytokines. Monocyte chemoattractant protein-1 (MCP-1) is an inflammatory cytokine, produced predominantly by macrophages and endothelial cells, and is expressed in adipose tissue. More recently it has been shown that PTH administration increases MCP-1 expression in osteoblasts.', 'Because both PTH and MCP-1 levels are higher in obesity, the goal was to determine whether the high MCP-1 occurs only in the presence of high serum PTH and is independent of adiposity and examine its relationship with bone mineral density (BMD) and turnover.', 'In this case-control clinical design, 111 eligible women were categorized into four groups: leaner women [body mass index (BMI) 23 ± 2 kg/m(2)] with normal or higher PTH and obese (BMI 44 ± 7 kg/m(2)) with normal or higher PTH.', 'Serum MCP-1 levels were higher (P < 0.01) in the high (PTH = 74.9 ± 27.0 pg/ml, MCP-1 = 421.5 ± 157.0 pg/ml) compared with normal PTH (PTH = 32.5 ± 10.4 pg/ml, MCP-1 = 322.5 ± 97.8 pg/ml) group, independent of BMI. C-reactive protein and adiponectin were influenced only by BMI and not PTH. MCP-1 was positively associated with osteocalcin and propeptide of type 1 collagen in the leaner (r > 0.3, P < 0.05) but not the obese women and was not associated with BMD in either group.'] |
['Duodenal obstruction occurs in 1 of 6000 live births and requires urgent surgical intervention. Duodenal atresia previously has been ascribed to a developmental failure of luminal recanalization; however, the cause of duodenal atresia remains incompletely understood. Although familial intestinal atresias have been described and syndromic associations are known, no specific genetic link has been established. Fibroblast growth factor-10 (Fgf10) is a known regulatory molecule relevant to mesenchymal-epithelial interactions, and mice deficient in Fgf10 demonstrate congenital anomalies in several organ systems including the gastrointestinal tract. The authors hypothesized that Fgf10 could serve a regulatory role in establishing normal duodenal development.', 'Wild-type mice with beta-galactosidase under the control of the Fgf10 promoter were harvested from timed-pregnancy mothers. The expression of Fgf10 in the duodenum during development was evaluated by developing the embryos in X-Gal solution. Wild-type and mutant Fgf10(-/-) embryos were harvested from timed-pregnancy mothers at 18.5 days postconception (near term) and were analyzed for duodenal morphology (Institutional Animal Care and Use Committee-approved protocol 32-02). Photomicrographs were reviewed.', 'Fibroblast growth factor-10 is active in the duodenum at a late stage of development. The Fgf10(-/-) mutants demonstrate duodenal atresia with a variable phenotype similar to clinical findings. The duodenum fails to develop luminal continuity and has proximal dilation. The phenotype occurs in an autosomal recessive pattern with incomplete penetrance (38%).'] |
['To compare hypothalamus-pituitary-adrenal (HPA) axis integrity at diagnosis and recovery after transsphenoidal surgery (TSS), in acromegaly patients, compared with tumor size matched non-functioning adenoma (NFA) patients.', 'A retrospective 7-year evaluation of acromegaly patients, who underwent TSS with 52\xa0weeks follow-up at a single institution, was undertaken. 50 acromegaly with complete follow-up data at all points and 50 NFA patients were matched for tumor size; HPA axis was similarly assessed pre-operatively and at 6, 12 and 52\xa0weeks post-operatively. Recovery of HPA axis and gender specific prevalence of adrenal insufficiency (AI), were analyzed in both groups. We also studied AI in acromegaly patients requiring medical therapy post-operatively vs those in remission after surgery.', 'AI remained less prevalent in acromegaly vs NFA (acromegaly, p\xa0=\xa00.01; NFA, p\xa0=\xa00.15) at 52\xa0weeks after surgery, although the prevalence of AI decreased in both groups from baseline by 52\xa0weeks. Additionally, recovery from baseline AI was significantly greater by 52\xa0weeks in acromegaly patients over NFA patients (p\xa0=\xa00.001). Recovery of HPA axis in acromegaly patients remained significant (p\xa0=\xa00.03) despite the need for medical therapy. AI at baseline was proportionately more prevalent in acromegalic males at baseline (p\xa0=\xa00.002) but no gender difference was apparent at 52\xa0weeks (p\xa0=\xa00.35). Conversely, in NFA patients, no gender difference was apparent pre-operatively (p\xa0=\xa00.49), but AI was more prevalent in males at 52\xa0weeks (p\xa0=\xa00.001).'] |
['Periodic limb movements of sleep (PLMS) are common in the elderly. However, no large polysomnographic study has closely examined the relationship of PLMS to sleep architecture and arousals from sleep. We investigated the prevalence and correlates of PLMS in a community-based sample of older women.', 'Observational study, cross-sectional analyses.', 'Two clinical sites participating in the Study of Osteoporotic Fractures (SOF).', '455 older community-dwelling women (mean age 82.9 years) who completed in-home polysomnography at SOF visit 8.', 'N/A.', 'In-home 12 channel polysomnography was performed with measurement of leg movements by bilateral piezo sensors. Measures of PLMS included the number of leg movements per hour of sleep (PLMI) and the number of leg movements causing EEG-documented arousals per hour of sleep (PLMA). An elevated PLMI was common, with 66% showing PLMI > or =5 and 52% showing PLMI > or =15. A PLMA > or =5 and > or =15 were observed in 124 (27%) and 26 (6%) participants respectively. After adjustment for the potential confounders of antidepressant medication use, age, race, body mass index, and apnea-hypopnea index, participants with a higher PLMA had a significantly higher arousal index, lower sleep efficiency, higher percentages of sleep stages 1 and 2 and lower percentages of stages 3-4 and REM (p < .001). An increased PLMI was associated with a higher arousal index, but not with other indices of sleep quality. Neither PLMI or PMLA was associated with subjective sleepiness or other known comorbidities.'] |
['Portal fibroblasts are newly identified, potentially fibrogenic liver cells that are distinct from hepatic stellate cells. The ectonucleotidase* nucleoside triphosphate diphosphohydrolase 2 (NTPDase2) is restricted to portal fibroblasts in the normal liver. However, the fate of NTPDase2 after bile duct ligation (BDL) is unknown.', 'The aim of this study was to assess the effect of experimental rat and disease-mediated human biliary cirrhosis on NTPDase2 expression in the liver.', 'Cirrhosis was induced in experimental rats via BDL and carbon tetrachloride (CCl4) administration. Archived human liver biopsy specimens from normal liver, primary biliary cirrhosis, or hepatitis C cirrhosis were examined. Changes in expression of NTPDase2 were determined using confocal immunofluorescence, immunoblot, and real-time polymerase chain reaction.', 'Confocal immunofluorescence demonstrated a decrease in NTPDase2 expression after BDL. Immunoblot and real-time polymerase chain reaction demonstrated a decrease in NTPDase2 expression by portal fibroblasts after BDL. No decrease in NTPDase2 protein was noted after CCl4 administration, and NTPDase2 messenger ribonucleic acid was markedly up-regulated after CCl4 administration. Confocal immunofluorescence demonstrated a shift of NTPDase2 expression from portal areas to central areas that colocalized with alpha-smooth muscle actin after CCl4 administration. In human biopsy specimens, NTPDase2 expression was lost in cirrhosis owing to primary biliary cirrhosis, whereas NTPDase2 expression was shifted to bridging fibrous bands in cirrhosis owing to hepatitis C.'] |
['The platelets (PLTs) in PLT concentrates are counted with hematology analyzers, but varying results among different hematology analyzers are observed, making comparisons very difficult. Due to the absence of red blood cells in PLT concentrates, the International Council for Standardization in Hematology (ICSH) reference method was modified to be used for PLT concentrates and validated in an international comparative study.', 'Five PLT samples were shipped to eight participating centers of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative and counted on the same day. PLTs were stained with fluorescein isothiocyanate-labeled anti-CD41a in tubes (TruCount, BD Biosciences), measured on a flow cytometer, and analyzed with a uniform template. These samples were also counted on 15 hematology analyzers.', 'The ICSH method and newly developed BEST method yielded PLT counting results with less than 1% difference (not significant). The intercenter coefficient of variation (CV) of the BEST method was on average 6.3% versus 7.6% on average for hematology analyzers. The CV of individual hematology analyzers was on average 0.9%, which was considerably lower than for the flow cytometers with a mean of 3.7%.'] |
['For patients with epithelial ovarian cancer (EOC) cytoreduction, with a combination of taxane and platinum, is the standard of care. Despite this, approximately 50% of patients with advanced disease will relapse and moreover 15-20% of cases of EOC are resistant to platinum based chemotherapy. Vascular Endothelial Growth Factor (VEGF), an angiogenic factor, is associated with poor prognosis. This study was undertaken to examine whether there is an association between VEGF-A expression in the tumour of EOC patients and their response to platinum based chemotherapy.', 'The study cohort consisted of 66 patients with advanced stage EOC (FIGO III-IV). Ovarian cancer tissue was analysed for VEGF-A expression immunohistochemically. Protein expression was measured and correlated, with platinum sensitivity and overall patient survival.', 'Median age of patients was 53 years, 45 patients had platinum sensitive disease (68%), the remaining patients being platinum resistant (32%). Of the platinum resistant group, 18 (86%) patients had high VEGF score compared to only 1 (2%) with high VEGF score in the platinum sensitive group. Median survival was 11 months in the patient group with high VEGF score versus 32 months in that cohort with low VEGF score. VEGF expression was significantly inversely correlated with overall survival (P < 0.0001).'] |
['Elcatonin (ECT) is used to prevent and treat osteoporosis. However, little is known about its effect on the disuse osteoporosis (DOP). The aim of this study is to evaluate the effect of ECT on DOP caused by fracture fixation.', 'Forty-five male Sprague-Dawley (SD) rats, aged 6 weeks, were randomly allocated into three groups: the control group without surgery and elcatonin treatment (CTR, n = 15), the surgery group without elcatonin treatment (SUR, n = 15), and the surgery group which received elcatonin subcutaneously (SUR + ECT, n = 15). Surgery was produced by cutting the midshaft of the right femur transversely, fixing with stainless intramedullary needle, and immobilizing the right leg. All the proximal tibias from the random five rats in each group were harvested and investigated by evaluating bone mineral density (BMD), X-ray images, and histological staining respectively at the 4th, 8th, and 12th weeks after surgery.', 'Both of the SUR and SUR + ECT groups obviously exhibited lower BMD values compared to the CTR group; however, the SUR + ECT group showed significantly higher BMD values (p < 0.001, p < 0.05, and p < 0.05) than the SUR group at each time point after surgery. Moreover, similar changes were observed between these groups when examining the radiographs and hematoxylin and eosin (HE) staining.'] |
['To elucidate whether miR-216b suppresses cell proliferation and invasion by targeting PKCα, thus to reveal the molecular mechanism that miR-216b functions as a tumor suppressor in nasopharyngeal carcinoma (NPC).', "PKCα 3'UTR-luciferase vector was constructed and dual-luciferase reporter gene assay was employed to examine the effect of miR-216b on luciferase activity. Nasopharyngeal cancer CNE2 cells were transfected with miR-216b mimics, and then qRT-PCR and Western blotting were performed to detect the expressions of PKCa mRNA and protein. The effects of PKCα downregulation on cell proliferation and invasion were assessed after PKCα siRNA were transfected into CNE2 cells. CNE2 cells were cotransfected with miR-216b mimics and PKCα plasmid, and the proliferation of CNE2 cells was assayed using a MTS cell proliferation assay kit.", "The results of dual-luciferase reporter gene assay demonstrated that miR-216b could bind to the 3'-untranslated region (UTR) of PKCα and inhibited the luciferase activity to 62.4% of that of the mimics control cells. The expressions of PKCα mRNA and protein were significantly down-regulated by 49.1% and 55.7%, respectively, in comparison with that of the control cells. siRNA-mediated downregulation of PKCα suppressed the proliferation and invasion ability of CNE2 cells, and could partially mimic the tumor-inhibiting effect of miR-216b. Moreover, the overexpressed PKCα may partially reverse the inhibitory effect of miR-216b on proliferation of CNE2 cells."] |
['Factors affecting the stability of intertrochanteric fractures when elderly patients fall are few to be reported. In this retrospective study, possible factors were investigated.', 'Two hundred and twenty-three consecutive elderly patients (≥65 years) with intertrochanteric fractures due to low energy injuries were studied. Patient age, gender, body mass index (BMI), body weight and height were compared between fractures with stable (AO/OTA type A1, intact lesser trochanter, 80 patients) and unstable (AO/OTA types A2, A3, displaced lesser trochanter or reverse obliquity fractures, 143 patients) types. Statistical approaches with univariate and multivariate analyses were performed.', 'There was no statistical difference in patient gender, age, body weight or height between patients with stable and unstable fractures in both univariate and multivariate analysis. However, BMI was statistically higher in patients with unstable fractures (22.7 vs 21.4, p\xa0=\xa00.01) in univariate analysis, but without a difference in multivariate analysis (p\xa0=\xa00.07).'] |
['The aim of this study is to examine the effects of taurine supplementation on homocysteine (Hcy) metabolism and liver injury in rats fed a choline-deficient diet.', 'Thirty rats were divided into three groups (n=10), to receive one of the following diets for 4 weeks: control diet (C), choline-deficient diet (CDD), or choline-deficient diet supplemented with taurine (CDDT). The CDD and the CDDT consisted of AIN-93 without the recommended choline content of 2.5%, and the CDDT was supplemented by the addition of 2.5% taurine.', 'Four weeks of ingesting a CDD resulted in a significant increase in plasma Hcy (50%) as well as a decrease in liver S-adenosylmethionine (SAM) concentration and S-adenosylmethionine/S-adenosylhomocysteine ratio. No changes were found in plasma methionine and cysteine plasma levels compared to control group. Four weeks of ingesting a CDD also caused a significant (P<0.05) increase in hepatic total fat, hepatic malondialdehyde (MDA), and plasma alanine aminotransferase (ALT) levels. In addition, reduced hepatic glutathione (GSH) levels and reduced/oxidized glutathione ratios (GSH/GSSG) were found in rats fed a CDD compared to controls. Taurine supplementation of the CDD normalized genes involved in the remethylation pathway, BHMT and CHDH, which were impaired by CDD alone. However, taurine supplementation failed to prevent CDD-induced Hcy metabolism disturbances and hepatic injury. Also, taurine added to CDD caused decreased expression of PEMT, CHKa, and CHKb, key genes involved in phosphatidylcholine (PC) synthesis and liver fat accumulation.'] |
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