905 resultados para Multiple-effect
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Context: There is great interindividual variability in the response to recombinant human (rh) GH therapy in patients with Turner syndrome (TS). Ascertaining genetic factors can improve the accuracy of growth response predictions. Objective: The objective of the study was to assess the individual and combined influence of GHR-exon 3 and -202 A/C IGFBP3 polymorphisms on the short-and long-term outcomes of rhGH therapy in patients with TS. Design and Patients: GHR-exon 3 and -202 A/C IGFBP3 genotyping (rs2854744) was correlated with height data of 112 patients with TS who remained prepubertal during the first year of rhGH therapy and 65 patients who reached adult height after 5 +/- 2.5 yr of rhGH treatment. Main Outcome Measures: First-year growth velocity and adult height were measured. Results: Patients carrying at least one GHR-d3 or -202 A-IGFBP3 allele presented higher mean first-year growth velocity and achieved taller adult heights than those homozygous for GHR-fl or -202 C-IGFBP3 alleles, respectively. The combined analysis of GHR-exon 3 and -202 A/C IGFBP3 genotypes showed a clear nonadditive epistatic influence on adult height of patients with TS treated with rhGH (GHR-exon 3 alone, R-2 = 0.27; -202 A/C IGFBP3, R-2 = 0.24; the combined genotypes, R-2 = 0.37 at multiple linear regression). Together with clinical factors, these genotypes accounted for 61% of the variability in adult height of patients with TS after rhGH therapy. Conclusion: Homozygosity for the GHR-exon3 full-length allele and/or the -202C-IGFBP3 allele are associated with less favorable short-and long-term growth outcomes after rhGH treatment in patients with TS. (J Clin Endocrinol Metab 97: E671-E677, 2012)
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Abstract Study design Controlled laboratory study. Objectives The purposes of this paper were to investigate (d) whether vastus medialis obliquus (VMO), vastus lateralis longus (VLL) and vastus lateralis obliquus (VLO) EMG activity can be influenced by hip abduction performed by healthy subjects. Background Some clinicians contraindicate hip abduction for patellofemoral patients (with) based on the premise that hip abduction could facilitate the VLL muscle activation leading to a VLL and VMO imbalance Methods and measures Twenty-one clinically healthy subjects were involved in the study, 10 women and 11 men (aged X = 23.3 ± 2.9). The EMG signals were collected using a computerized EMG VIKING II, with 8 channels and three pairs of surface electrodes. EMG activity was obtained from MVIC knee extension at 90° of flexion in a seated position and MVIC hip abduction at 0° and 30° with patients in side-lying position with the knee in full extension. The data were normalized in the MVIC knee extension at 50° of flexion in a seated position, and were submitted to ANOVA test with subsequent application of the Bonferroni multiple comparisons analysis test. The level of significance was defined as p ≤ 0.05. Results The VLO muscle demonstrated a similar pattern to the VMO muscle showing higher EMG activity in MVIC knee extension at 90° of flexion compared with MVIC hip abduction at 0° and 30° of abduction for male (p < 0.0007) and MVIC hip abduction at 0° of abduction for female subjects (p < 0.02196). There were no statistically significant differences in the VLL EMG activity among the three sets of exercises tested. Conclusion The results showed that no selective EMG activation was observed when comparison was made between the VMO, VLL and VLO muscles while performing MVIC hip abduction at 0° and 30° of abduction and MVIC knee extension at 90° of flexion in both male and female subjects. Our findings demonstrate that hip abduction do not facilitated VLL and VLO activity in relation to the VMO, however, this study included only healthy subjects performing maximum voluntary isometric contraction contractions, therefore much remains to be discovered by future research
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Mutations in solute carrier family 26 (sulfate transporter), member 2 (SLC26A2) gene result in a spectrum of autosomal recessive chondrodysplasias that range from the mildest recessive form of multiple epiphysial dysplasia (rMED) through the most common diastrophic dysplasia (DTD) to lethal atelosteogenesis type II and achondrogenesis IB. The clinical variability has been ascribed to quantitative effect of mutations of the sulfate transporter activity. Here we describe two Brazilian sisters, born to healthy and non consanguineous parents, with Robin sequence, mild shortening of upper and lower limbs, brachymetacarpalia/tarsalia, additional and accelerated carpal ossification, marked genu valgum, and multiple epiphysial dysplasia. This phenotype was intermediate between DTD and rMED, and both girls have a compound heterozygous mutations for the SLC26A2, a Finnish founder mutation (c.-26?+?2T>C), and R279W. This combination of mutations has been observed in individuals with different phenotypes, including DTD, DTD variant, and rMED. The distinct phenotype of our cases reinforces the hypothesis that other factors may be influencing the phenotype as previously suggested.
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The aim of this study was to evaluate the effect of irrigation regimens on dentin microhardness at the furcation area of mandibular molars, using sodium hypochlorite and ethylenediaminetetraacetic acid (EDTA), individually and in alternation. The occlusal surface and the roots of 20 non-carious extracted human permanent mandibular molars were cut transversally and discarded. The tooth blocks were embedded in acrylic resin and randomly assigned to 4 groups (n=5) according to the irrigating regimens: 1% NaOCl solution, 17% EDTA solution, 1% NaOCl and 17% EDTA and distilled water (control). Knoop microhardness of dentin at the furcation area was evaluated. Data were analyzed using one-way ANOVA and Tukey's multiple comparison tests (α=0.05). The results of this study indicated that all irrigation solutions, except for distilled water (control), decreased dentin microhardness. EDTA did not show a significant difference with NaOCl/EDTA (p>0.05), but showed a significant difference with NaOCl (p<0.01). EDTA and NaOCl/EDTA showed a maximum decrease in microhardness. The 17% EDTA solution, either alone or in combination with 1% NaOCl reduced significantly dentin microhardness at the furcation area of mandibular molars.
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The objective of this study is to provide empirical evidence on how ownership structure and owner’s identity affect performance, in the banking industry by using a panel of Indonesia banks over the period 2000–2009. Firstly, we analysed the impact of the presence of multiple blockholders on bank ownership structure and performance. Building on multiple agency and principal-principal theories, we investigated whether the presence and shares dispersion across blockholders with different identities (i.e. central and regional government; families; foreign banks and financial institutions) affected bank performance, in terms of profitability and efficiency. We found that the number of blockholders has a negative effect on banks’ performance, while blockholders’ concentration has a positive effect. Moreover, we observed that the dispersion of ownership across different types of blockholders has a negative effect on banks’ performance. We interpret such results as evidence that, when heterogeneous blockholders are present, the disadvantage from conflicts of interests between blockholders seems to outweigh the advantage of the increase in additional monitoring by additional blockholder. Secondly, we conducted a joint analysis of the static, selection, and dynamic effects of different types of ownership on banks’ performance. We found that regional banks and foreign banks have a higher profitability and efficiency as compared to domestic private banks. In the short-run, foreign acquisitions and domestic M&As reduce the level of overhead costs, while in the long-run they increase the Net Interest Margin (NIM). Further, we analysed NIM determinants, to asses the impact of ownership on bank business orientation. Our findings lend support to our prediction that the NIM determinants differs accordingly to the type of bank ownership. We also observed that banks that experienced changes in ownership, such as foreign-acquired banks, manifest different interest margin determinants with respect to domestic or foreign banks that did not experience ownership rearrangements.
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Hypoxia-inducible factor-1 alpha (HIF-1α) plays a critical role in survival and is associated with poor prognosis in solid tumors. The role of HIF-1α in multiple myeloma is not completely known. In the present study, we explored the effect of EZN2968, an locked nucleic acid antisense oligonucleotide against HIF-1α, as a molecular target in MM. A panel of MM cell lines and primary samples from MM patients were cultured in vitro in the presence of EZN2968 . Under normoxia culture condition, HIF-1α mRNA and protein expression was detectable in all MM cell lines and in CD138+ cells from newly diagnosed MM patients samples. Significant up-regulation of HIF-1α protein expression was observed after incubation with IL6 or IGF-I, confirming that HIF-1α can be further induced by biological stimuli. EZN2968 efficiently induces a selective and stable down-modulation of HIF-1α and decreased the secretion of VEGF released by MM cell. Treatment with EZN2968 gave rise to a progressive accumulation of cells in the S and subG0 phase. The analysis of p21, a cyclin-dependent kinase inhibitors controlling cell cycle check point, shows upregulation of protein levels. These results suggest that HIF-1α inhibition is sufficient for cell cycle arrest in normoxia, and for inducing an apoptotic pathways.. In the presence of bone marrow microenvironment, HIF-1α inhibition blocks MAPK kinase pathway and secretion of pro-surviaval cytokines ( IL6,VEGF,IL8) In this study we provide evidence that HIF-1α, even in the absence of hypoxia signal, is expressed in MM plasma cells and further inducible by bone marrow milieu stimuli; moreover its inhibition is sufficient to induce a permanent cell cycle arrest. Our data support the hypothesis that HIF-1α inhibition may suppress tumor growth by preventing proliferation of plasma cells through p21 activation and blocking pro-survival stimuli from bone marrow microenvironment.
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Recent studies support the notion that statins, widely prescribed cholesterol-lowering agents, may target key elements in the immunological cascade leading to inflammation and tissue damage in the pathogenesis of multiple sclerosis (MS). Compelling experimental and observational clinical studies highlighted the possibility that statins may also exert immunomodulatory synergy with approved MS drugs, resulting in several randomized clinical trials testing statins in combination with interferon-beta (IFN-?). Some data, however, suggest that this particular combination may not be clinically beneficial, and might actually have a negative effect on the disease course in some patients with MS. In this regard, a small North American trial indicated that atorvastatin administered in combination with IFN-? may increase disease activity in relapsing-remitting MS. Although other trials did not confirm this finding, the enthusiasm for studies with statins dwindled. This review aims to provide a comprehensive overview of the completed clinical trials and reports of the interim analyses evaluating the combination of IFN-? and statins in MS. Moreover, we try to address the evident question whether usage of this combination routinely requires caution, since the number of IFN-?-treated MS patients receiving statins for lowering of cholesterol is expected to grow.
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Clinically, the displacement of intravertebral fat into the circulation during vertebroplasty is reported to lead to problems in elderly patients and can represent a serious complication, especially when multiple levels have to be treated. An in vitro study has shown the feasibility of removing intravertebral fat by pulsed jet-lavage prior to vertebroplasty, potentially reducing the embolization of bone marrow fat from the vertebral bodies and alleviating the cardiovascular changes elicited by pulmonary fat embolism. In this in vivo study, percutaneous vertebroplasty using polymethylmethacrylate (PMMA) was performed in three lumbar vertebrae of 11 sheep. In six sheep (lavage group), pulsed jet-lavage was performed prior to injection of PMMA compared to the control group of five sheep receiving only PMMA vertebroplasty. Invasive recording of blood pressures was performed continuously until 60 min after the last injection. Cardiac output and arterial blood gas parameters were measured at selected time points. Post mortem, the injected cement volume was measured using CT and lung biopsies were processed for assessment of intravascular fat. Pulsed jet-lavage was feasible in the in vivo setting. In the control group, the injection of PMMA resulted in pulmonary fat embolism and a sudden and significant increase in mean pulmonary arterial pressure. Pulsed jet-lavage prevented any cardiovascular changes and significantly reduced the severity of bone marrow fat embolization. Even though significantly more cement had been injected into the lavaged vertebral bodies, significantly fewer intravascular fat emboli were identified in the lung tissue. Pulsed jet-lavage prevented the cardiovascular complications after PMMA vertebroplasty in sheep and alleviated the severity of pulmonary fat embolism.
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Objective: To compare the soft and hard tissue healing and remodeling around tissue-level implants with different neck configurations after at least 1 year of functional loading. Material and methods: Eighteen patients with multiple missing teeth in the posterior area received two implants inserted in the same sextant. One test (T) implant with a 1.8 mm turned neck and one control (C) implant with a 2.8 mm turned neck were randomly assigned. All implants were placed transmucosally to the same sink depth of approximately 1.8 mm. Peri-apical radiographs were obtained using the paralleling technique and digitized. Two investigators blinded to the implant type-evaluated soft and hard tissue conditions at baseline, 6 months and 1 year after loading. Results: The mean crestal bone levels and soft tissue parameters were not significantly different between T and C implants at all time points. However, T implants displayed significantly less crestal bone loss than C implants after 1 year. Moreover, a frequency analysis revealed a higher percentage (50%) of T implants with crestal bone levels 1–2 mm below the implant shoulder compared with C implants (5.6%) 1 year after loading. Conclusion: Implants with a reduced height turned neck of 1.8 mm may, indeed, lower the crestal bone resorption and hence, may maintain higher crestal bone levels than do implants with a 2.8 mm turned neck, when sunk to the same depth. Moreover, several factors other than the vertical positioning of the moderately rough SLA surface may influence crestal bone levels after 1 year of function.
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We and others found two polymorphic LRRK2 (leucine-rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first sequenced the coding regions in young onset and familial PD patients and identified 59 variants. We then examined these variants in 250 patients and 250 control subjects. Among the 17 polymorphic variants, five demonstrated different frequency in cases versus controls and were considered in a larger sample of 1,363 patients and 1,251 control subjects. The relative risk of an individual with both p.G2385R and p.R1628P is about 1.9, and this is reduced to 1.5-1.6 if the individual also carries rs7133914:G>C; p.R1398H or rs7308720:C>A: p.N551K. The risk of a carrier with p.R1628P is largely negated if the individual also carries p.R1398H or p.N551K. In dopaminergic neuronal lines, p.R1398H had significantly lower kinase activity, whereas p.G2385R and p.R1628P showed higher kinase activity than wild type. We provided the first evidence that multiple LRRK2 variants exert an individual effect and together modulate the risk of PD among Chinese.
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Excessive consumption of acidic drinks and foods contributes to tooth erosion. The aims of the present in vitro study were twofold: (1) to assess the erosive potential of different dietary substances and medications; (2) to determine the chemical properties with an impact on the erosive potential. We selected sixty agents: soft drinks, an energy drink, sports drinks, alcoholic drinks, juice, fruit, mineral water, yogurt, tea, coffee, salad dressing and medications. The erosive potential of the tested agents was quantified as the changes in surface hardness (ΔSH) of enamel specimens within the first 2 min (ΔSH2-0 = SH2 min - SHbaseline) and the second 2 min exposure (ΔSH4-2 = SH4 min - SH2 min). To characterise these agents, various chemical properties, e.g. pH, concentrations of Ca, Pi and F, titratable acidity to pH 7·0 and buffering capacity at the original pH value (β), as well as degree of saturation (pK - pI) with respect to hydroxyapatite (HAP) and fluorapatite (FAP), were determined. Erosive challenge caused a statistically significant reduction in SH for all agents except for coffee, some medications and alcoholic drinks, and non-flavoured mineral waters, teas and yogurts (P < 0·01). By multiple linear regression analysis, 52 % of the variation in ΔSH after 2 min and 61 % after 4 min immersion were explained by pH, β and concentrations of F and Ca (P < 0·05). pH was the variable with the highest impact in multiple regression and bivariate correlation analyses. Furthermore, a high bivariate correlation was also obtained between (pK - pI)HAP, (pK - pI)FAP and ΔSH.
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The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2mg, and tropisetron 5mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.
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In this study, the effect of time derivatives of flow rate and rotational speed was investigated on the mathematical modeling of a rotary blood pump (RBP). The basic model estimates the pressure head of the pump as a dependent variable using measured flow and speed as predictive variables. Performance of the model was evaluated by adding time derivative terms for flow and speed. First, to create a realistic working condition, the Levitronix CentriMag RBP was implanted in a sheep. All parameters from the model were physically measured and digitally acquired over a wide range of conditions, including pulsatile speed. Second, a statistical analysis of the different variables (flow, speed, and their time derivatives) based on multiple regression analysis was performed to determine the significant variables for pressure head estimation. Finally, different mathematical models were used to show the effect of time derivative terms on the performance of the models. In order to evaluate how well the estimated pressure head using different models fits the measured pressure head, root mean square error and correlation coefficient were used. The results indicate that inclusion of time derivatives of flow and speed can improve model accuracy, but only minimally.
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Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. The present study evaluated the effect of atorvastatin added to interferon beta-1b in multiple sclerosis (MS) in a multicenter, randomized, parallel-group, rater-blinded study performed in eight Swiss hospitals. Seventy-seven patients with relapsing-remitting MS started interferon beta-1b every other day. After 3 months, they were randomized 1:1 to receive atorvastatin 40 mg/day or not in addition to interferon beta-1b until month 15. The primary endpoint was the proportion of patients with new lesions on T2-weighted images at month 15 compared to baseline at month three. At study end, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.14; 95 % CI 0.36-3.56; p = 0.81). All predefined secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of new Gd-enhancing lesions on T1-weighted images, total brain volume, volume of grey matter, volume of white matter, EDSS, MSFC, relapse rate, time to first relapse, number of relapse-free patients and neutralizing antibodies did not show any significant differences (all p values >0.1). Transient elevations of liver enzymes were more frequent with atorvastatin (p = 0.02). In conclusion, atorvastatin 40 mg/day in addition to interferon beta-1b did not have a beneficial effect on relapsing-remitting MS compared to interferon beta-1b monotherapy over a 12-month period.