Massive Osteolytic Lesion of the Femur after Total Knee Arthroplasty.

Various failure mechanisms have been identified in total knee arthroplasty (TKA). We hereby present one case of failure, which stands out because of its rapid and destructive progression. We report the case of a 72-year-old Caucasian female patient who developed a large bone osteolytic lesion of the femur after TKA. The patient presented to our hospital 7 years after the initial surgery, complaining of persistent knee pain. The lesion affected the distal half of the femur and, after a diagnostic workup, required a resection of 20 cm and reconstruction with a tumor prosthesis. Subsequent pathological analysis revealed a reaction to cement and prosthesis components. Periprosthetic osteolysis continues to be a major problem, and a reaction to cement and prosthesis components can be an elusive cause of TKA failure.info:eu-repo/semantics/publishedVersio

A critical overview of computational approaches employed for COVID-19 drug discovery

COVID-19 has resulted in huge numbers of infections and deaths worldwide and brought the most severe disruptions to societies and economies since the Great Depression. Massive experimental and computational research effort to understand and characterize the disease and rapidly develop diagnostics, vaccines, and drugs has emerged in response to this devastating pandemic and more than 130 000 COVID-19-related research papers have been published in peer-reviewed journals or deposited in preprint servers. Much of the research effort has focused on the discovery of novel drug candidates or repurposing of existing drugs against COVID-19, and many such projects have been either exclusively computational or computer-aided experimental studies. Herein, we provide an expert overview of the key computational methods and their applications for the discovery of COVID-19 small-molecule therapeutics that have been reported in the research literature. We further outline that, after the first year the COVID-19 pandemic, it appears that drug repurposing has not produced rapid and global solutions. However, several known drugs have been used in the clinic to cure COVID-19 patients, and a few repurposed drugs continue to be considered in clinical trials, along with several novel clinical candidates. We posit that truly impactful computational tools must deliver actionable, experimentally testable hypotheses enabling the discovery of novel drugs and drug combinations, and that open science and rapid sharing of research results are critical to accelerate the development of novel, much needed therapeutics for COVID-19

Self-administered questionnaire versus interview as a screening method for intimate partner violence in the prenatal setting in Japan: A randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Intimate partner violence (IPV) is a serious social issue in Japan. In order to start effective interventions for abused women, the appropriate method of screening for IPV in healthcare settings needs clarifying. The objective of this study was to compare the effectiveness of a face-to-face interview with a self-administered questionnaire. We used the Violence Against Women Screen (VAWS), a Japanese screening instrument for intimate partner violence (IPV), for identifying pregnant women who have experienced abuse.</p> <p>Methods</p> <p>We conducted a randomised controlled trial to screen participants at three points in time in a prenatal clinic in Tokyo, Japan. There were 328 consenting women between 14 and 25 weeks of pregnancy who were consecutively selected and randomly assigned to either the interview or self-administered questionnaire group. Both groups completed the same screening instrument three times during their pregnancy. The primary outcome was the total number of women identified by each screening method and the secondary outcome was the effect of the screening as measured by the women's comfort level and their expressed need to consult with the nurse.</p> <p>Results</p> <p>For all three screenings, the identification rate in the interview group was significantly lower than that for the self-administered questionnaire group (relative risk 0.66, 95% CI 0.46 to 0.97), even after controlling for smoking (adjusted odds ratio 0.59, 95% CI 0.35 to 0.98). The two groups did not differ for secondary outcomes.</p> <p>Conclusions</p> <p>The self-administered questionnaire identified more IPV than the face-to-face interview when screening pregnant women in a Japanese prenatal clinic.</p> <p>Trial Registration</p> <p>UMIN-CTRC000000353</p

CACHE (Critical Assessment of Computational Hit-finding Experiments): A public–private partnership benchmarking initiative to enable the development of computational methods for hit-finding

One aspirational goal of computational chemistry is to predict potent and drug-like binders for any protein, such that only those that bind are synthesized. In this Roadmap, we describe the launch of Critical Assessment of Computational Hit-finding Experiments (CACHE), a public benchmarking project to compare and improve small-molecule hit-finding algorithms through cycles of prediction and experimental testing. Participants will predict small-molecule binders for new and biologically relevant protein targets representing different prediction scenarios. Predicted compounds will be tested rigorously in an experimental hub, and all predicted binders as well as all experimental screening data, including the chemical structures of experimentally tested compounds, will be made publicly available and not subject to any intellectual property restrictions. The ability of a range of computational approaches to find novel binders will be evaluated, compared and openly published. CACHE will launch three new benchmarking exercises every year. The outcomes will be better prediction methods, new small-molecule binders for target proteins of importance for fundamental biology or drug discovery and a major technological step towards achieving the goal of Target 2035, a global initiative to identify pharmacological probes for all human proteins. [Figure not available: see fulltext.

DNA multigene characterization of Fasciola hepatica and Lymnaea neotropica and its fascioliasis transmission capacity in Uruguay, with historical correlation, human report review and infection risk analysis

Fascioliasis is a highly pathogenic zoonotic disease emerging in recent decades, in part due to the effects of climate and global changes. South America is the continent presenting more numerous human fascioliasis endemic areas and the highest Fasciola hepatica infection prevalences and intensities known in humans. These serious public health scenarios appear mainly linked to altitude areas in Andean countries, whereas lowland areas of non-Andean countries, such as Uruguay, only show sporadic human cases or outbreaks. To understand this difference, we characterized F. hepatica from cattle and horses and lymnaeids of Uruguay by sequencing of ribosomal DNA ITS-2 and ITS-1 spacers and mitochondrial DNA cox1, nad1 and 16S genes. Results indicate that vectors belong to Lymnaea neotropica instead of to Lymnaea viator, as always reported from Uruguay. Our correlation of fasciolid and lymnaeid haplotypes with historical data on the introduction and spread of livestock species into Uruguay allow to understand the molecular diversity detected. We study the life cycle and transmission features of F. hepatica by L. neotropica of Uruguay under standardized experimental conditions to enable a comparison with the transmission capacity of F. hepatica by Galba truncatula at very high altitude in Bolivia. Results demonstrate that although L. neotropica is a highly efficient vector in the lowlands, its transmission capacity is markedly lower than that of G. truncatula in the highlands. On this baseline, we review the human fascioliasis cases reported in Uruguay and analyze the present and future risk of human infection in front of future climate change estimations

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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