488 research outputs found

    Collapse-related bone changes at multidetector CT in ARCO 1-2 osteonecrotic femoral heads: correlation with clinical and MRI data.

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    OBJECTIVE: To assess the frequency of collapse-related bone changes at multi-detector CT (MDCT) in osteonecrotic femoral heads (ONFH) and to compare clinical parameters and MRI findings in Association Research Circulation Osseous (ARCO) 1-2 ONFH with or without collapse-related bone changes (CRBC) at MDCT. MATERIALS AND METHODS: This is a secondary analysis of radiographic, MRI, and MDCT examinations of ONFH of patients eligible for a prospective clinical trial. Radiographs and MRI were analyzed to perform ARCO staging. Frequency of CRBC at MDCT including cortical interruption, trabecular interruption, impaction, and resorption was determined by two readers (R1, R2) blinded to radiographic, MRI, and clinical data. Baseline clinical and imaging data of ARCO 1-2 ONFH were compared between hips with or without CRBC at MDCT. RESULTS: One hundred thirty-two hips of 77 participants were analyzed. There were 78 non-collapsed and 54 collapsed ONFH. For R1 and R2, 31/78 (40%) and 20/78 (26%) ARCO 1-2 ONFH and 54/54 (100%) and 53/54 (98%) ARCO 3-4 ONFH showed at least one CRBC at MDCT. For both readers, there was no significant difference in pain, functional impairment, size of lesion, and the presence of BME on MRI between ARCO 1-2 hips with or without CRBC at MDCT. CONCLUSION: Twenty-six to forty percent of ARCO 1-2 ONFH demonstrate at least one collapse-related bone change at CT. Their clinical and MRI findings do not differ from those without collapse-related bone changes

    TEACHERS’ PERCEPTIONS OF PERSONAL AND ENVIRONMENTAL ATTRIBUTES INDICATIVE OF THEMATICAL CREATIVITY IN ETHNIC MINORITY, HIGH SCHOOL STUDENTS, AS REFLECTED IN A DYNAMIC SYSTEM MODEL OF CREATIVE PROBLEM-SOLVING ABILITY

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    This research project has been formulated as a thematic, deductive, qualitative study to investigate teachers’ perceptions of the creative problem-solving ability (CPSA) dynamic system model(Cho, 1999, 2003) in determining problem-solving ability in mathematics (CPSAM). In the dynamic system model, Cho proposed that six attributes, namely convergent thinking, divergent thinking, motivation, knowledge and skills, and environment, are essential for creative problem-solving ability. Two quantitative studies, Lin and Cho (2011) and Teseo (2018) examined the six attributes of the dynamic system model as predictors for problem-solving ability in mathematics. To understand the teachers’ perceptions of the application of the CPSA attributes in the dynamic system model to students’ CPSAM, in the present qualitative study, I focused on the teachers’ assessment of the model. The teachers had to formulate their responses to six open-ended research questions to address the inquiry of the suitability of the dynamic system model in determining the creative problem-solving ability in mathematics for ethnic minority high school students. They were also invited to express their opinion on whether the six attributes could be placed in a hierarchical order of importance or the attributes formed a coherent integral unit. Finally, the participants were invited to provide their own model in place of the dynamic system model. Teachers were purposefully sampled and invited and the final pool comprised instructors who offer AP and other higher order courses from three different disciplines. The data were collected as semi structured email interviews and also as limited telephone and face-to-face interviews. The information extracted from the interviews were allocated to prior themes to determine the perceptions expressed by the teachers. The thematic qualitative analysis method was undertaken in this study. Overall, 25 teachers responded to the invitation, and the sample included all the disciplines attempted for inclusion. There was a unanimous acceptance of the dynamic system model. In fact, 80% of the teachers expressed a hierarchical preference by placing the environmental attribute at the top of the list, followed by prior knowledge and motivation, and from these attributes they believed a nurtured ability for divergent thinking would evolve. None of the participants gave any credence to convergent thinking as playing a role in CPSAM. It became evident from the teachers’ perceptions that they thought the environment played a major role in developing creativity. Specifically, parental involvement, school climate, and their own contributions formulated pedagogies that nurture and promote creative thinking in their classes

    Intergenerational programming during the pandemic: Transformation during (constantly) changing times

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    Intergenerational programs have long been employed to reduce ageism and optimize youth and older adult development. Most involve in-person meetings, which COVID-19 arrested. Needs for safety and social contact were amplified during COVID-19, leading to modified programming that engaged generations remotely rather than eliminating it. Our collective case study incorporates four intergenerational programs in five US states prior to and during COVID-19. Each aims to reduce ageism, incorporating nutrition education, technology skills, or photography programming. Authors present case goals, participants, implementation methods, including responses to COVID-19, outcomes, and lessons learned. Technology afforded opportunities for intergenerational connections; non-technological methods also were employed. Across cases, programmatic foci were maintained through adaptive programming. Community partners’ awareness of immediate needs facilitated responsive programming with universities, who leveraged unique resources. While new methods and partnerships will continue post-pandemic, authors concurred that virtual contact cannot fully substitute for in-person relationship-building. Remote programming maintained ties between groups ready to resume shared in-person programming as soon as possible; they now have tested means for responding to routine or novel cancellations of in-person programming. Able to implement in-person and remote intergenerational programming, communities can fight ageism and pursue diverse goals regardless of health, transportation, weather, or other restrictions

    Human carbamylome description identifies carbamylated α2-macroglobulin and hemopexin as two novel autoantigens in early rheumatoid arthritis

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    Objectives: Anti-carbamylated protein antibodies (anti-CarPA) are present in rheumatoid arthritis (RA) sera and have been associated with erosive disease. The exact targets of anti-CarPA in vivo are currently not well known; we used a proteomic approach on serum and synovial fluid (SF) of RA patients to assess the human carbamylome and to identify carbamylated autoantigens as potential biomarkers in early RA. Methods: Mass spectrometry was performed on SF and serum from RA patients. Carbamylated proteins present in both sample types were selected as candidate autoantigens for the establishment of ELISAs. A cohort of early RA patients was tested for positivity for specific anti-CarPA. Results: Eleven novel carbamylated proteins were identified, and five were selected as potential autoantigens for detection of anti-CarPA. Among them, antibodies against carbamylated Hemopexin (anti-CaHPX) and Alpha-2-macroglobulin (anti-CaA2M) showed comparable diagnostic value to the established carbamylated fetal calf serum-based ELISA. A cohort of 189 early RA patients was studied. The combination of these new biomarkers with antibodies against citrullinated peptides and rheumatoid factor identified 89% of early RA patients in our cohort. There was little correlation between the tested biomarkers, and each one of the tested antigens could identify a different subset of seronegative RA patients. Anti-CaA2M positivity showed clinical potential, being associated with higher disease disability. Conclusion: We highlight the detection of novel carbamylated autoantigens in vivo using a combined proteomic approach in SF and serum of RA patients. Anti-CaHPX and anti-CaA2M are promising clinical biomarkers, especially in seronegative RA

    The Rise in Cardiovascular Risk Factors and Chronic Diseases in Guyana: A Narrative Review

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    Background: Guyana experiences health challenges related to both communicable and non-communicable diseases. Cardiovascular disease (CVD) is the most common non-communicable disease in Guyana. The main causes of the increased prevalence of non-communicable diseases are modifiable risk factors (e.g. obesity, hypertension, elevated cholesterol, unhealthy dietary patterns) and non-modifiable risk factors (e.g. age and genetics). Objective: The aim of this review is to understand CVD and risk factor data, in the context of ethnicity in Guyana. Methods: A review of the published literature as well as government and international health agency reports was conducted. All publications from 2002–2018 describing CVD and related risk factors in Guyana were screened and extracted. Findings: The population of Guyana is comprised of six ethnic groups, of which East Indian (39.8%) and African (29.3%) are the majority. CVD accounts for 526 deaths per 100,000 individuals per year. Among Indo-Guyanese and Afro-Guyanese, CVD is the primary cause of death affecting 32.6% and 22.7% of the populations, respectively. Within the Indo-Guyanese and Afro-Guyanese communities there is a high prevalence of hypertension and diabetes among individuals over the age of 50. There is a lack of available data describing ethnic disparities in CVD and related risk factors such as obesity, smoking, alcohol, physical activity and diet in Guyana. Conclusions: Important knowledge gaps remain in understanding the ethnic disparities of CVD and related risk factors in Guyana. Future research should focus on high risk populations and implement widespread screening and treatment strategies of common risk factors such as hypertension, diabetes, and elevated cholesterol to curb the epidemic of CVD in Guyana

    Effects of Hydroxyurea Treatment on Haemolysis in Patients with Sickle Cell Disease at Muhimbili National Hospital, Tanzania

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    Tanzania is one of the countries with a high burden of sickle cell disease (SCD). Haemolytic anaemia is a clinical feature of SCD, and has been linked to major complications leading to morbidity and mortality. Treatment with hydroxyurea (HU) has shown to induce foetal haemoglobin (HbF) which in turn decreases haemolysis in patients. This study aimed to investigate the effects of HU on haemolysis in SCD patients attending Muhimbili National Hospital, Tanzania by comparing their haemolytic parameters before and after therapy. Patients meeting the criteria were initiated on HU therapy for 3 months. Two haemolytic biomarkers: unconjugated plasma bilirubin levels and absolute reticulocyte counts were measured from patients’ blood samples at baseline and after 3 months of HU therapy and compared. Both absolute reticulocyte counts and indirect plasma bilirubin levels significantly declined after HU therapy. Median (IQR) plasma unconjugated bilirubin levels dropped significantly from 20.3 (12.7–34.4) μmol/L to 14.5 (9.6–24.1) μmol/L (p < 0.001) and mean (SD) absolute reticulocyte counts dropped significantly from 0.29 (0.1) x 109/L to 0.17 (0.1) x 109/L (p < 0.001) after therapy, thus, a decline in both haemolytic biomarkers after treatment was observed. This study found a potential for use of HU therapy in managing SCD patients in our settings evidenced by improvements in their haemolytic parameters. Clinical trials with a lager sample size conducted for a longer time period would be beneficial in guiding towards the inclusion of HU in treatment protocols for the Tanzanian population. Keywords: Sickle cell disease; hydroxyurea; haemolysis; foetal haemoglobin &nbsp

    CHARACTERIZING GLYCOSAMINOGLYCAN AND GLYCOSAMINOGLYCAN-OLIGO INTERACTIONS WITH CANCER STEM CELLS AND THEIR REGULATORS

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    Tumor metastasis and recurrence account for more than 90% of cancer-associated deaths and are thought to occur due to a small subpopulation of neoplastic cells known as cancer stem cells (CSCs). Because CSCs are resistant to conventional chemotherapy, there is a critical need to develop CSC-targeting agents. Microenvironmental components, especially glycosaminoglycans (GAGs), play a key role in regulating CSC phenotype. GAGs such as heparan sulfate (HS) interact with hundreds of proteins and influence a variety of biological processes including tumor proliferation, angiogenesis, metastasis and stem cell biology. Recently, the Desai and Patel laboratories have demonstrated that a hexasaccharide form of HS, HS06, inhibits CSC self-renewal in multiple cancer cell lines, while shorter/longer chains are less potent. To explore potential mechanisms driving this phenomenon, this work aimed to devise a biophysical screening methodology to identify CSC-relevant protein targets of HS06. This was accomplished using fluorescence spectroscopy in combination with computational docking assays. Our methodology identified several new, CSC-relevant proteins that bound HS06 with nanomolar affinity. Furthermore, chain-length dependent patterns were observed for HS binding to IGF-1, IGF-1R and the IGF-1/IGF-1R complex (a key regulator of CSCs), providing a plausible explanation for prior cell-based observations that HS06 inhibits IGF-1R activation while longer chains enhance activation. The second aim of this work was to study HS06’s ability to target CSCs, both in vitro and in vivo, in comparison to 2-O,3-O-desulfated heparin (ODSH), a nonanticoagulant GAG-derivative currently in multiple cancer clinical trials. Using preliminary in vitro screens, we observed that HS06 inhibited CSCs while longer nonanticoagulant GAGs like ODSH did not. This was confirmed in vivo, where HS06 was more effective at inhibiting tumor growth and CSC self-renewal in an HT-29 xenograft mouse model compared to ODSH. In conclusion, despite little attention being paid towards the study of GAG-oligos in literature, our work demonstrates that such molecules demonstrate significant therapeutic promise. These preliminary results indicate that in contrast to longer polymers such as ODSH, GAG-oligos like HS06 warrant further attention in translational/clinical studies aimed at developing anti-CSC agents

    Original Full Length Article Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: Five year follow-up of a prospective controlled study

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    Objective: To determine the efficacy of bone marrow cell implantation into the necrotic lesion of the femoral head on clinical symptoms and the progression of osteonecrosis of the femoral head in comparison with core decompression. Methods: We studied nineteen patients and twenty four hips with early stage osteonecrosis of the femoral head. The hips were allocated to either core decompression only or core decompression and implantation of bone marrow cells. Both patients and assessors were blind with respect to treatment group assignment. The primary outcomes were clinical symptoms and disease progression. Results: Bone marrow implantation afforded a significant reduction in pain and in joint symptoms and reduced the incidence of fractural stages. At 60 months, eight of the eleven hips in the control group had deteriorated to the fractural stage whereas only three of the thirteen hips in the bone marrow graft group had progressed to that stage. Survival analysis showed a significant difference in the time to failure between the two groups at 60 months. Patients had only minor side-effects after the treatments. Conclusions: This long term follow-up study confirmed that implantation of autologous bone marrow cells in the necrotic lesion might be an effective treatment for patients with early stages of osteonecrosis of the femoral head

    Antibodies against carbamylated proteins: prevalence and associated disease characteristics in Belgian patients with rheumatoid arthritis or other rheumatic diseases.

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    OBJECTIVES: Anti-carbamylated protein antibodies (anti-CarP) are reported to be associated with increased disease activity and with more severe joint damage in rheumatoid arthritis (RA) patients. The present study investigated the presence of anti-CarP in various rheumatic diseases, and their specific clinical significance in RA, in Belgian rheumatology patients. METHOD: We tested sera from 254 RA patients, 56 healthy controls, and 153 patients with different rheumatic conditions: juvenile idiopathic arthritis (JIA), axial spondyloarthritis, systemic sclerosis, and Sjögren's syndrome (SS). An in-house enzyme-linked immunosorbent assay was used to detect immunoglobulin G antibodies against carbamylated foetal calf serum. RESULTS: Anti-CarP were detected in 88 RA patients (34.6%), of whom 82% were also positive for anti-citrullinated protein antibodies (ACPAs) and 81% were also rheumatoid factor (RF) positive. Of note, 11 anti-CarP single-positive patients were detected (4.3%). The previously reported association with joint erosions was not detected. However, in ACPA- and RF-negative RA patients, the presence of anti-CarP was associated with higher disease activity and disability. Fifteen per cent of JIA patients and 30% of SS patients also tested positive for anti-CarP and their antibody levels did not differ significantly from those of anti-CarP-positive RA patients. Anti-CarP levels were, however, significantly higher in ACPA- or RF-positive patients. CONCLUSION: Anti-CarP antibodies were detected in the sera of a cohort of Belgian RA patients. Moreover, they were also detected in primary SS patients and in JIA patients. In the seronegative subset of RA patients, anti-CarP antibodies showed prognostic value
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