329 research outputs found

    Probing the Formation of Reactive Oxygen Species by a Porous Self- Assembled Benzophenone Bis-Urea Host

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    Herein, we examine the photochemical formation of reactive oxygen species (ROS) by a porous benzophenone-containing bis-urea host (1) to investigate the mechanism of photooxidations that occur within the confines of its nanochannels. UV irradiation of the self-assembled host in the presence of molecular oxygen generates both singlet oxygen and superoxide when suspended in solution. The efficiency of ROS generation by the host is lower than that of benzophenone (BP), which could be beneficial for reactions carried out catalytically, as ROS species react quickly and often unselectively. Superoxide formation was detected through reaction with 5,5- dimethyl-1-pyrroline N-oxide in the presence of methanol. However, it is not detected in CHCl3, as it reacts rapidly with the solvent to generate methaneperoxy and chloride anions, similar to BP. The lifetime of airborne singlet oxygen (τΔairborne) was examined at the air−solid outer surface of the host and host·quencher complexes and suggests that quenching is a surface phenomenon. The efficiency of the host and BP as catalysts was compared for the photooxidation of 1-methyl-1-cyclohexene in solution. Both the host and BP mediate the photooxidation in CHCl3, benzene, and benzene-d6, producing primarily epoxide-derived products with low selectivity likely by both type I and type II photooxidation processes. Interestingly, in CHCl3, two chlorohydrins were also formed, reflecting the formation of chloride in this solvent. In contrast, UV irradiation of the host·guest crystals in an oxygen atmosphere produced no epoxide and appeared to favor mainly the type II processes. Photolysis afforded high conversion to only three products: an enone, a tertiary allylic alcohol, and a diol, which demonstrates the accessibility of the encapsulated reactants to oxygen and the influence of confinement on the reaction pathway

    Arthroscopic observation was useful to detect loosening of the femoral component of unicompartmental knee arthroplasty in a recurrent hemoarthrosis

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    A case of recurrent hemarthrosis of the knee after a mobile-bearing unicompartmental knee arthroplasty (UKA; Oxford UKA) is described. A 58-year-old man met with a road traffic accident 10 months after UKA. He developed anteromedial pain and hemarthrosis of the knee joint 1 month after the accident, which required multiple aspirations. Physical examination showed no instability. Plain radiograph revealed no signs of loosening. All laboratory data, including bleeding and coagulation times, were within normal limits. Diagnostic arthroscopy demonstrated loosening of the femoral component. Any intraarticular pathology other than nonspecific synovitis was ruled out. The loose femoral component and polyethylene meniscal bearing were revised. Since then, hemarthrosis has not recurred

    Bursaries, writing grants and fellowships: a strategy to develop research capacity in primary health care

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    BACKGROUND: General practitioners and other primary health care professionals are often the first point of contact for patients requiring health care. Identifying, understanding and linking current evidence to best practice can be challenging and requires at least a basic understanding of research principles and methodologies. However, not all primary health care professionals are trained in research or have research experience. With the aim of enhancing research skills and developing a research culture in primary health care, University Departments of General Practice and Rural Health have been supported since 2000 by the Australian Government funded 'Primary Health Care Research Evaluation and Development (PHCRED) Strategy'. A small grant funding scheme to support primary health care practitioners was implemented through the PHCRED program at Flinders University in South Australia between 2002 and 2005. The scheme incorporated academic mentors and three types of funding support: bursaries, writing grants and research fellowships. This article describes outcomes of the funding scheme and contributes to the debate surrounding the effectiveness of funding schemes as a means of building research capacity. METHODS: Funding recipients who had completed their research were invited to participate in a semi-structured 40-minute telephone interview. Feedback was sought on acquisition of research skills, publication outcomes, development of research capacity, confidence and interest in research, and perception of research. Data were also collected on demographics, research topics, and time needed to complete planned activities. RESULTS: The funding scheme supported 24 bursaries, 11 writing grants, and three research fellows. Nearly half (47%) of all grant recipients were allied health professionals, followed by general practitioners (21%). The majority (70%) were novice and early career researchers. Eighty-nine percent of the grant recipients were interviewed. Capacity, confidence, and level of research skills in ten core areas were generally considered to have improved as a result of the award. More than half (53%) had presented their research and 32% had published or submitted an article in a peer-reviewed journal. CONCLUSION: A small grant and mentoring scheme through a University Department can effectively enhance research skills, confidence, output, and interest in research of primary health care practitioners

    Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

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    Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research

    Metabolic Effects of Acute Thiamine Depletion Are Reversed by Rapamycin in Breast and Leukemia Cells

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    Thiamine-dependent enzymes (TDEs) control metabolic pathways that are frequently altered in cancer and therefore present cancer-relevant targets. We have previously shown that the recombinant enzyme thiaminase cleaves and depletes intracellular thiamine, has growth inhibitory activity against leukemia and breast cancer cell lines, and that its growth inhibitory effects were reversed in leukemia cell lines by rapamycin. Now, we first show further evidence of thiaminase therapeutic potential by demonstrating its activity against breast and leukemia xenografts, and against a primary leukemia xenograft. We therefore further explored the metabolic effects of thiaminase in combination with rapamycin in leukemia and breast cell lines. Thiaminase decreased oxygen consumption rate and increased extracellular acidification rate, consistent with the inhibitory effect of acute thiamine depletion on the activity of the TDEs pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes; these effects were reversed by rapamycin. Metabolomic studies demonstrated intracellular thiamine depletion and the presence of the thiazole cleavage product in thiaminase-treated cells, providing validation of the experimental procedures. Accumulation of ribose and ribulose in both cell lines support the thiaminase-mediated suppression of the TDE transketolase. Interestingly, thiaminase suppression of another TDE, branched chain amino ketoacid dehydrogenase (BCKDH), showed very different patterns in the two cell lines: in RS4 leukemia cells it led to an increase in BCKDH substrates, and in MCF-7 breast cancer cells it led to a decrease in BCKDH products. Immunoblot analyses showed corresponding differences in expression of BCKDH pathway enzymes, and partial protection of thiaminase growth inhibition by gabapentin indicated that BCKDH inhibition may be a mechanism of thiaminase-mediated toxicity. Surprisingly, most of thiaminase-mediated metabolomic effects were also reversed by rapamycin. Thus, these studies demonstrate that acute intracellular thiamine depletion by recombinant thiaminase results in metabolic changes in thiamine-dependent metabolism, and demonstrate a previously unrecognized role of mTOR signaling in the regulation of thiamine-dependent metabolism

    Early intervention for adolescents with Patellofemoral Pain Syndrome - a pragmatic cluster randomised controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Self-reported knee pain is highly prevalent among adolescents. As much as 50% of the non-specific knee pain may be attributed to Patellofemoral Pain Syndrome (PFPS). In the short term, exercise therapy appears to have a better effect than patient education consisting of written information and general advice on exercise or compared with placebo treatment. But the long-term effect of exercise therapy compared with patient education is conflicting. The purpose of this study is to examine the short- and long-term effectiveness of patient education compared with patient education and multimodal physiotherapy applied at a very early stage of the condition among adolescents.</p> <p>Methods/Design</p> <p>This study is a single blind pragmatic cluster randomised controlled trial. Four upper secondary schools have been invited to participate in the study (approximately 2500 students, aged 15-19 years). Students are asked to answer an online questionnaire regarding musculoskeletal pain. The students who report knee pain are contacted by telephone and offered a clinical examination by a rheumatologist. Subjects who fit the inclusion criteria and are diagnosed with PFPS are invited to participate in the study. A minimum of 102 students with PFPS are then cluster-randomised into two intervention groups based on which school they attend. Both intervention groups receive written information and education. In addition to patient education, one group receives multimodal physiotherapy consisting primarily of neuromuscular training of the muscles around the foot, knee and hip and home exercises.</p> <p>The students with PFPS fill out self-reported questionnaires at baseline, 3, 6, 12 and 24 months after inclusion in the study. The primary outcome measure is perception of recovery measured on a 7-point Likert scale ranging from "completely recovered" to "worse than ever" at 12 months.</p> <p>Discussion</p> <p>This study is designed to investigate the effectiveness of patient education compared with patient education combined with multimodal physiotherapy. If patient education and multimodal physiotherapy applied at an early stage of Patellofemoral Pain Syndrome proves effective, it may serve as a basis for optimising the clinical pathway for those suffering from the condition, where specific emphasis can be placed on early diagnosis and early treatment.</p> <p>Trial Registration</p> <p>clinicaltrials.gov reference: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01438762">NCT01438762</a></p

    A community faith centre based screening and educational intervention to reduce the risk of type 2 diabetes: A feasibility study

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    AIMS: People of South Asian origin experience higher rates of diabetes and complications of diabetes compared to white Europeans. Therefore, it is important to identify those with undiagnosed diabetes and those at high risk of developing diabetes, in order to intervene with lifestyle intervention to reduce risk and prevent complications. We conducted a study to assess the feasibility of delivering a faith centre based pathway for screening and referral to group education for high risk individuals to increase screening uptake and reduce diabetes risk. METHODS: Opportunistic screening and early intervention strategy for people at risk of diabetes and cardiovascular disease in local faith centres. The screening consisted of a diabetes risk assessment tool and a near patient test for HbA1c. Participants found to be at high risk of diabetes (HbA1c 6-6.4%/42-46mmol/mol) were offered a 'Walking Away from Diabetes' group educational intervention aimed at increasing exercise levels and reducing diabetes risk. RESULTS: 252 participants were screened during four screening events. 202 participants (80.2%) gave consent for their data to be included in the analysis. 72.4% of participants were found to have a high diabetes risk score. 32 participants (15.8%) had a HbA1c result (6-6.4%/42-46mmol/mol). Eight participants (4.0%) had a (HbA1c ⩾6.5%/⩾47mmol/mol). Of those eligible for the diabetes prevention education programme, 18 participants (56.3%) attended. CONCLUSIONS: This study confirms that screening followed by group education within faith centre settings is feasible and acceptable to participants. The strategies chosen were effective in achieving a high screening yield and high uptake of group education

    Local Ca2+ Entry Via Orai1 Regulates Plasma Membrane Recruitment of TRPC1 and Controls Cytosolic Ca2+ Signals Required for Specific Cell Functions

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    Store-operated Ca2+ entry (SOCE) has been associated with two types of channels: CRAC channels that require Orai1 and STIM1 and SOC channels that involve TRPC1, Orai1, and STIM1. While TRPC1 significantly contributes to SOCE and SOC channel activity, abrogation of Orai1 function eliminates SOCE and activation of TRPC1. The critical role of Orai1 in activation of TRPC1-SOC channels following Ca2+ store depletion has not yet been established. Herein we report that TRPC1 and Orai1 are components of distinct channels. We show that TRPC1/Orai1/STIM1-dependent ISOC, activated in response to Ca2+ store depletion, is composed of TRPC1/STIM1-mediated non-selective cation current and Orai1/STIM1-mediated ICRAC; the latter is detected when TRPC1 function is suppressed by expression of shTRPC1 or a STIM1 mutant that lacks TRPC1 gating, STIM1(684EE685). In addition to gating TRPC1 and Orai1, STIM1 mediates the recruitment and association of the channels within ER/PM junctional domains, a critical step in TRPC1 activation. Importantly, we show that Ca2+ entry via Orai1 triggers plasma membrane insertion of TRPC1, which is prevented by blocking SOCE with 1 µM Gd3+, removal of extracellular Ca2+, knockdown of Orai1, or expression of dominant negative mutant Orai1 lacking a functional pore, Orai1-E106Q. In cells expressing another pore mutant of Orai1, Orai1-E106D, TRPC1 trafficking is supported in Ca2+-containing, but not Ca2+-free, medium. Consistent with this, ICRAC is activated in cells pretreated with thapsigargin in Ca2+-free medium while ISOC is activated in cells pretreated in Ca2+-containing medium. Significantly, TRPC1 function is required for sustained KCa activity and contributes to NFκB activation while Orai1 is sufficient for NFAT activation. Together, these findings reveal an as-yet unidentified function for Orai1 that explains the critical requirement of the channel in the activation of TRPC1 following Ca2+ store depletion. We suggest that coordinated regulation of the surface expression of TRPC1 by Orai1 and gating by STIM1 provides a mechanism for rapidly modulating and maintaining SOCE-generated Ca2+ signals. By recruiting ion channels and other signaling pathways, Orai1 and STIM1 concertedly impact a variety of critical cell functions that are initiated by SOCE
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