3,925 research outputs found

    The Classic: Functional Results of Hip Arthroplasty with Acrylic Prosthesis

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    This Classic article is a reprint of the original work by R. Merle d’Aubigné and M. Postel, Functional Results of Hip Arthroplasty with Acrylic Prosthesis. An accompanying biographical sketch on R. Merle d’Aubigné, MD, is available at DOI 10.1007/s11999-008-0571-2. The Classic Article is ©1954 by the Journal of Bone and Joint Surgery, Inc. and is reprinted with permission from Merle d’Aubigné R, Postel M. Functional results of hip arthroplasty with acrylic prosthesis. J Bone Joint Surg Am. 1954;35:451--475

    Geographical trends in research: a preliminary analysis on authors' affiliations

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    In the last decade, research literature reached an enormous volume with an unprecedented current annual increase of 1.5 million new publications. As research gets ever more global and new countries and institutions, either from academia or corporate environment, start to contribute with their share, it is important to monitor this complex scenario and understand its dynamics. We present a study on a conference proceedings dataset extracted from Springer Nature Scigraph that illustrates insightful geographical trends and highlights the unbalanced growth of competitive research institutions worldwide. Results emerged from our micro and macro analysis show that the distributions among countries of institutions and papers follow a power law, and thus very few countries keep producing most of the papers accepted by high-tier conferences. In addition, we found that the annual and overall turnover rate of the top 5, 10 and 25 countries is extremely low, suggesting a very static landscape in which new entries struggle to emerge. Finally, we highlight the presence of an increasing gap between the number of institutions initiating and overseeing research endeavours (i.e. first and last authors' affiliations) and the total number of institutions participating in research. As a consequence of our analysis, the paper also discusses our experience in working with affiliations: an utterly simple matter at first glance, that is instead revealed to be a complex research and technical challenge yet far from being solved

    Outbreak of West Nile virus causing severe neurological involvement in children, Nuba Mountains, Sudan, 2002.

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    An atypical outbreak of West Nile virus (WNV) occurred in Ngorban County, South Kordophan, Sudan, from May to August 2002. We investigated the epidemic and conducted a case-control study in the village of Limon. Blood samples were obtained for cases and controls. Patients with obvious sequelae underwent cerebrospinal fluid (CSF) sampling as well. We used enzyme-linked immunosorbent assay (ELISA) and neutralization tests for laboratory diagnosis and identified 31 cases with encephalitis, four of whom died. Median age was 36 months. Bivariate analysis did not reveal any significant association with the risk factors investigated. Laboratory analysis confirmed presence of IgM antibodies caused by WNV in eight of 13 cases, indicative of recent viral infection. The unique aspects of the WNW outbreak in Sudan, i.e. disease occurrence solely among children and the clinical domination of encephalitis, involving severe neurological sequelae, demonstrate the continuing evolution of WNV virulence. The spread of such a virus to other countries or continents cannot be excluded

    Left ventricular non-compaction: clinical features and cardiovascular magnetic resonance imaging

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    Background: It is apparent that despite lack of family history, patients with the morphological characteristics of left ventricular non-compaction develop arrhythmias, thrombo-embolism and left ventricular dysfunction. METHODS: Forty two patients, aged 48.7 +/- 2.3 yrs (mean +/- SEM) underwent cardiovascular magnetic resonance (CMR) for the quantification of left ventricular volumes and extent of non-compacted (NC) myocardium. The latter was quantified using planimetry on the two-chamber long axis LV view (NC area). The patients included those referred specifically for CMR to investigate suspected cardiomyopathy, and as such is represents a selected group of patients. RESULTS: At presentation, 50% had dyspnoea, 19% chest pain, 14% palpitations and 5% stroke. Pulmonary embolism had occurred in 7% and brachial artery embolism in 2%. The ECG was abnormal in 81% and atrial fibrillation occurred in 29%. Transthoracic echocardiograms showed features of NC in only 10%. On CMR, patients who presented with dyspnoea had greater left ventricular volumes (both p < 0.0001) and a lower left ventricular ejection fraction (LVEF) (p < 0.0001) than age-matched, healthy controls. In patients without dyspnoea (n = 21), NC area correlated positively with end-diastolic volume (r = 0.52, p = 0.0184) and end-systolic volume (r = 0.56, p = 0.0095), and negatively with EF (r = -0.72, p = 0.0001). CONCLUSION: Left ventricular non-compaction is associated with dysrrhythmias, thromboembolic events, chest pain and LV dysfunction. The inverse correlation between NC area and EF suggests that NC contributes to left ventricular dysfunction

    Trends in incidence of recorded diagnosis of osteoporosis, osteopenia, and fragility fractures in people aged 50 years and above: retrospective cohort study using UK primary care data

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    Summary This study used primary care data to estimate the incidence of recorded diagnosis of osteoporosis, osteopenia, and fragility fracture in the UK during 2000–2018 accounting for age, sex, calendar year and social deprivation. More than 3 million people aged 50–99 years were included. We found that men living in the most deprived areas had a 45% higher risk of being diagnosed with osteoporosis and 50% higher risk of fragility fracture compared to men living in the least deprived areas. Purpose a) To estimate the incidence trends of a recorded diagnosis of osteoporosis, osteopenia, and fragility fracture in the UK over time; b) to describe differences according to age, sex, and social deprivation. Methods This is a longitudinal population-based cohort study using routinely collected primary care data obtained via IQVIA Medical Research Database (IMRD). All patients aged 50–99 years registered with a practice participating in THIN (The Health Improvement Network) between 2000–2018 were included. The first recorded diagnosis of osteoporosis, osteopenia, or fragility fracture was used to estimate incidence rates (IR) per 10,000 person-years at risk. Poisson regression was used to provide Incidence Rate Ratios (IRR) adjusted by age, sex, social deprivation, calendar year, and practice effect. Results The year-specific adjusted IRR of recorded osteoporosis was highest in 2009 in women [IRR 1.44(95%CI 1.38–1.50)], whereas in men it was highest in 2013–2014 [IRR 1.94(95%CI 1.72–2.18)] compared to 2000. The year-specific adjusted IRR of fragility fracture was highest in 2012 in women [IRR 1.77(95%CI 1.69–1.85)], whereas in men it was highest in 2013 [IRR 1.64(95%CI 1.51–1.78)] compared to 2000. Men in the most deprived areas had a higher risk of being diagnosed with osteoporosis [IRR 1.45(95%CI 1.38–1.53)], osteopenia [IRR 1.17(95%CI 1.09–1.26)], and fragility fracture [IRR 1.50(95%CI 1.44–1.56)] compared to those living in the least deprived areas, but smaller differences were seen in women. Conclusion Use of fracture risk assessment tools may enhance the detection of osteoporosis cases in primary care. Further research is needed on the effect of social deprivation on diagnosis of osteoporosis and fractures

    Sunscreens - Which and what for?

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    It is well established that sun exposure is the main cause for the development of skin cancer. Chronic continuous UV radiation is believed to induce malignant melanoma, whereas intermittent high-dose UV exposure contributes to the occurrence of actinic keratosis as precursor lesions of squamous cell carcinoma as well as basal cell carcinoma. Not only photocarcinogenesis but also the mechanisms of photoaging have recently become apparent. In this respect the use of sunscreens seemed to prove to be more and more important and popular within the last decades. However, there is still inconsistency about the usefulness of sunscreens. Several studies show that inadequate use and incomplete UV spectrum efficacy may compromise protection more than previously expected. The sunscreen market is crowded by numerous products. Inorganic sunscreens such as zinc oxide and titanium oxide have a wide spectral range of activity compared to most of the organic sunscreen products. It is not uncommon for organic sunscreens to cause photocontact allergy, but their cosmetic acceptability is still superior to the one given by inorganic sunscreens. Recently, modern galenic approaches such as micronization and encapsulation allow the development of high-quality inorganic sunscreens. The potential systemic toxicity of organic sunscreens has lately primarily been discussed controversially in public, and several studies show contradictory results. Although a matter of debate, at present the sun protection factor (SPF) is the most reliable information for the consumer as a measure of sunscreen filter efficacy. In this context additional tests have been introduced for the evaluation of not only the protective effect against erythema but also protection against UV-induced immunological and mutational effects. Recently, combinations of UV filters with agents active in DNA repair have been introduced in order to improve photoprotection. This article reviews the efficacy of sunscreens in the prevention of epithelial and nonepithelial skin cancer, the effect on immunosuppression and the value of the SPF as well as new developments on the sunscreen market. Copyright (C) 2005 S. Karger AG, Basel

    Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China.

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    A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women's Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95% confidence interval [CI]: 1.0, 1.4 [0.8-2.5], and 2.2 [1.2-4.0], respectively; P trend = 0.003). Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030). Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations

    A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

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    Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties

    Arabidopsis MKS1 Is Involved in Basal Immunity and Requires an Intact N-terminal Domain for Proper Function

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    Innate immune signaling pathways in animals and plants are regulated by mitogen-activated protein kinase (MAPK) cascades. MAP kinase 4 (MPK4) functions downstream of innate immune receptors via a nuclear substrate MKS1 to regulate the activity of the WRKY33 transcription factor, which in turn controls the production of anti-microbial phytoalexins.We investigate the role of MKS1 in basal resistance and the importance of its N- and C-terminal domains for MKS1 function. We used the information that mks1 loss-of-function partially suppresses the mpk4 loss-of-function phenotype, and that transgenic expression of functional MKS1 in mpk4/mks1 double mutants reverted the mpk4 dwarf phenotype. Transformation of mks1/mpk4 with mutant versions of MKS1 constructs showed that a single amino acid substitution in a putative MAP kinase docking domain, MKS1-L32A, or a truncated MKS1 version unable to interact with WRKY33, were deficient in reverting the double mutant to the mpk4 phenotype. These results demonstrate functional requirement in MKS1 for the interaction with MPK4 and WRKY33. In addition, nuclear localization of MKS1 was shown to depend on an intact N-terminal domain. Furthermore, loss-of-function mks1 mutants exhibited increased susceptibility to strains of Pseudomonas syringae and Hyaloperonospora arabidopsidis, indicating that MKS1 plays a role in basal defense responses.Taken together, our results indicate that MKS1 function and subcellular location requires an intact N-terminus important for both MPK4 and WRKY33 interactions
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