Podcasts about methods four

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.16.253385v1?rss=1 Authors: Dong, G.-H. Abstract: Background: Animal models suggest transitions from non-addictive to addictive behavioral engagement are associated with ventral-to-dorsal striatal shifts. However, few studies have examined such features in humans, especially in internet gaming disorder (IGD), a behavioral addiction. Methods: Four-hundred-and-eighteen subjects (174 with IGD; 244 with recreational game use (RGU)) were recruited. Resting-state fMRI data were collected and functional connectivity (FC) analyses were performed based on ventral and dorsal striatal seeds. Correlations and follow-up spectrum dynamic causal model (spDCM) analyses were performed to examine relationships between ventral/dorsal striatum to medial frontal gyrus (MFG) and IGD severity. Longitudinal data from 40 subjects (22 IGD; 18 RGU) were also analysed to investigate further. Results: Interactions were observed between group (IGD, RGU) and striatal regions (ventral, dorsal). IGD relative to RGU subjects showed lower ventral-striatum-to-MFG (mostly involving supplementary motor area (SMA)) and higher dorsal-striatum-to-MFG functional connectivity. spDCM revealed that left dorsal-striatum-to-MFG connectivity was correlated with IGD severity. Longitudinal data further support for ventral-to-dorsal striatal MFG relationships in IGD. Conclusions: Consistent with animal models of substance addictions, ventral-to-dorsal striatal transitions in involvement coritico-striatal circuitry may underlie IGD and its severity. These findings suggest possible neurobiological mechanisms that may be targeted in treatments for IGD. Copy rights belong to original authors. Visit the link for more info

The decision to pull the trigger on a construction project is big. Your new space may give legs to a new business venture, spur company or product-line growth or provide a motivating space for your team. Once you have decided to move forward with your project, now what? This episode is loaded with information business owners can use to select the right team and path, or delivery method, to successfully complete their project. We offer a high-level perspective on each of the four delivery methods, including their distinctive advantages and disadvantages. Because there is so much to discuss on this topic, we will dissect each delivery method in upcoming episodes. Stay tuned!  www.bushconstruct.com 

Objective: Detection of disseminated tumor cells (DTCs) in the bone marrow (BM) of patients with breast cancer is associated with poor outcomes. Recent studies demonstrated that DTCs may serve as a prognostic factor in ovarian cancer. The aim of this 3-center study was to evaluate the impact of BM status on survival in a large cohort of patients with ovarian cancer. Materials and Methods: Four hundred ninety-five patients with primary ovarian cancer were included in this 3-center prospective study. Bone marrow aspirates were collected intraoperatively from the iliac crest. Disseminated tumor cells were identified by antibody staining and by cytomorphology. Clinical outcome was correlated with the presence of DTCs. Results: Disseminated tumor cells were detected in 27% of all BM aspirates. The number of cytokeratin-positive cells ranged from 1 to 42 per 2 x 10(6) mononuclear cells. Disseminated tumor cell status did correlate with histologic subtype but not with any of the other established clinicopathologic factors. The overall survival was significantly shorter among DTC-positive patients compared to DTC-negative patients (51 months; 95% confidence interval, 37-65 months vs 33 months; 95% confidence interval, 23-43 months; P = 0.023). In the multivariate analysis, BM status, International Federation of Gynecology and Obstetrics stage, nodal status, resection status, and age were independent predictors of reduced overall survival, whereas only BM status, International Federation of Gynecology and Obstetrics stage, and resection status independently predicted progression-free survival. Conclusions: Tumor cell dissemination into the BM is a common phenomenon in ovarian cancer. Disseminated tumor cell detection has the potential to become an important biomarker for prognostication and disease monitoring in patients with ovarian cancer.

Introduction: Keloids are the result of excessive scar tissue formation. Besides their poor aesthetic appearance, keloids can be associated with severe clinical symptoms such as pain, itching, and rigidity. Unfortunately, most therapeutic approaches remain clinically unsatisfactory. Recently, injections with botulinum toxin A (BTA) were proposed for the treatment of established keloids in a clinical trial. In this study, we aimed to verify the effects of intralesional BTA for the treatment of therapy-resistant keloids using objective measurements. In addition, the underlying molecular mechanisms were investigated using cultured keloid-derived fibroblasts. Materials and Methods: Four patients received BTA (doses varying from 70 to 140 Speywood units per session) injected directly into their keloids every 2 months for up to 6 months. Differences in height and volume were evaluated clinically and measured with a 3-D optical profiling system. Keloid-derived fibroblasts were treated with different concentrations of BTA, and expression of collagen (COL)1A1, COL1A2, COL3A1, TGF-beta 1, TGF-beta 2, TGF-beta 3, fibronectin-1, laminin-beta 2, and alpha-SMA was determined by real-time quantitative PCR. MTT and BrdU assays were used to analyze the effects of BTA on fibroblast proliferation and metabolism. Results: Intralesional administration of BTA did not result in regression of keloid tissue. No differences in expression of ECM markers, collagen synthesis, or TGF-beta could be observed after BTA treatment of keloid fibroblasts. In addition, cell proliferation and metabolism of keloid fibroblasts was not affected by BTA treatment. Conclusion: The suggested clinical efficiency of intralesional BTA for the therapy of existent keloids could not be confirmed in this study. Based on our data, the potential mechanisms of action of BTA on keloid-derived fibroblasts remain unclear. Copyright (C) 2012 S. Karger AG, Basel

Objectives: In artisanal small-scale gold mining (ASGM) areas in many developing countries, mercury (Hg) is used to extract gold from ore. Data of 1250 participants from Indonesia, Mongolia, Philippines, Tanzania, and Zimbabwe were combined to analyze the relation between exposure in ASGM areas and body burden. Methods: Four groups were selected relating to their intensity of contact with mercury: (i) a non-exposed control group; (ii) a low exposed group with participants only living in mining areas, but not working as miners; (iii) a medium exposed group, miners living in exposed areas and working with mercury without smelting amalgam; and (iv) a high exposed group, miners living in exposed areas and smelting amalgam. Results: Compared to the non-exposed control group, participants living and/or miners working in highly exposed areas have significantly higher concentration of total mercury in urine, hair and blood (p-value < 0.001). The median mercury value in urine in the control group is < 0.2 mu g/L. In the high exposed group of amalgam smelters, the median in urine is 12.0 mu g/L. The median in blood in the control group is < 0.93 mu g/L. The median level in blood of the high exposed group is 7.56 mu g/L. The median for mercury in hair samples from the control group is 0.21 mu g/g. In the high exposed group the median hair concentration is 2.4 mu g/g hair. Mercury levels also differ considerably between the countries, reflecting a diverse background burden due to different fish eating habits and different work place methods. Conclusions: A high percentage of exposed individuals had levels above threshold values. These high levels of mercury are likely to be related with serious health problems.

Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Basel

Background: Active dendritic cell (DC) immunization protocols are rapidly gaining interest as therapeutic options in patients with acute myeloid leukemia (AML). Here we present for the first time a GMP-compliant 3-day protocol for generation of monocyte-derived DCs using different synthetic Toll-like receptor (TLR) agonists in intensively pretreated patients with AML. Methods: Four different maturation cocktails were compared for their impact on cell recovery, phenotype, cytokine secretion, migration, and lymphocyte activation in 20 AML patients and 25 healthy controls. Results: Maturation cocktails containing the TLR7/8 agonists R848 or CL075, with and without the addition of the TLR3 agonist poly(I:C), induced DCs that had a positive costimulatory profile, secreted high levels of IL-12(p70), showed chemotaxis to CCR7 ligands, had the ability to activate NK cells, and efficiently stimulated antigen-specific CD8(+) T cells. Conclusions: Our results demonstrate that this approach translates into biologically improved DCs, not only in healthy controls but also in AML patients. This data supports the clinical application of TLR-matured DCs in patients with AML for activation of innate and adaptive immune responses.

Background: The increasing demand for complementary medicine indicates a change in attitudes regarding treatment understanding. Objectives: To investigate the role of attitudes in treatment motivation. (1) Can the study sample be subdivided into homogenous groups as regards attitudes toward complementary treatment? (2) How do these groups relate to motivational variables? Patients and Methods: Four questionnaires on motivation and attitudes were administered to 203 patients of two clinics for complementary medicine. Results were interpreted following Petry's motivational process model that distinguishes treatment disposition, preparedness for treatment and treatment activity. Results: According to a cluster analysis, 3 patient groups could be identified: `Not- convinced' patients (cluster 1, n = 24) demonstrated little conviction regarding any aspect of complementary treatment. `Convinced' patients (cluster 2, n = 103) showed a high degree of agreement on all three scales, being highest on `Role of patient'. `Partially- convinced' patients (cluster 3, n = 70) also evaluated `Role of patient' highest, but aspects of the `Physician- patient relationship' and the `Treatment method' were only partly regarded as important. In all clusters, the pragmatic motive of treatment acceptance was central for the treatment choice, but was highest in cluster 2. As compared to cluster 1, a complementary treatment understanding was higher in patients of clusters 2 and 3 ( highest in cluster 2). Discussion: Even if the pragmatic treatment motivation was high in all groups, the central role of treatment attitudes in the motivational process could be verified. Despite differing attitude structures, a majority of patients displayed a complementary treatment comprehension.