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    The Role of Single Positive Cultures in Presumed Aseptic Total Hip and Knee Revision Surgery—A Systematic Review of the Literature

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    Background: Prior to revision hip (THA) or knee arthroplasty (TKA), periprosthetic low-grade infection (PJI) should be ruled out. Despite advances in preoperative diagnosis, unsuspected positive cultures (UPCs) may occur in initially planned aseptic revisions. Particularly, single UPCs pose a diagnostic and therapeutic dilemma, as their impact on outcome is unclear and recommendations are heterogeneous. This review investigates the frequency of single UPCs and their impact on implant survivorship. Methods: In July 2022, a comprehensive literature search was performed using PubMed and Cochrane Library search. In total, 197 articles were screened. Seven retrospective studies with a total of 5821 cases were able to be included in this review. Results: Based on the cases included, UPCs were found in 794/5821 cases (14%). In 530/794 cases (67%), the majority of the UPCs were single positive. The most commonly isolated pathogens were coagulase negative Staphylococci and Cutibacterium acnes. Five of seven studies reported no influence on revision- or infection-free survival following a single positive culture. In two studies, single UPCs following THA revision were correlated with subsequent re-revision for PJI. Conclusions: Single UPCs of a non-virulent pathogen following presumed aseptic TKA revision may be interpreted as contaminants. A single UPC following THA revision may be a risk factor for subsequent PJI. The role of systemic antibiotic treatment remains unclear, but it should be considered if other risk factors for PJI are present

    Training interventions to reduce the risk of injury to the lower extremity joints during landing movements in adult athletes: a systematic review and meta-analysis

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    Objective: Aim of this systematic review was to summarise training interventions designed to reduce biomechanical risk factors associated with increased risk of lower extremity landing injuries and to evaluate their practical implications in amateur sports. Design: Systematic review and meta-analysis. Data sources: MEDLINE, Scopus and SPORTDiscus. Eligibility criteria: Training intervention(s) aimed at reducing biomechanical risk factors and/or injury rates included the following: (1) prospective or (non-)randomised controlled study design; (2) risk factors that were measured with valid two-dimensional or three-dimensional motion analysis systems or Landing Error Scoring System during jump landings. In addition, meta-analyses were performed, and the risk of bias was assessed. Results: Thirty-one studies met all inclusion criteria, capturing 11 different training interventions (eg, feedback and plyometrics) and 974 participants. A significantly medium effect of technique training (both instruction and feedback) and dynamic strengthening (ie, plyometrics with/without strengthening) on knee flexion angle (g=0.77; 95% CI 0.33 to 1.21) was shown. Only one-third of the studies had training interventions that required minimal training setup and additional coaching educations. Conclusion: This systematic review highlights that amateur coaches can decrease relevant biomechanical risk factors by means of minimal training setup, for example, instructing to focus on a soft landing, even within only one training session of simple technique training. The meta-analysis emphasises implementing technique training as stand-alone or combined with dynamic strengthening into amateur sport training routine

    Two-way Dispatched function in Sonic hedgehog shedding and transfer to high-density lipoproteins

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    The Sonic hedgehog (Shh) signaling pathway controls embryonic development and tissue homeostasis after birth. This requires regulated solubilization of dual-lipidated, firmly plasma membrane-associated Shh precursors from producing cells. Although it is firmly established that the resistance-nodulation-division transporter Dispatched (Disp) drives this process, it is less clear how lipidated Shh solubilization from the plasma membrane is achieved. We previously showed that Disp enhances proteolytic Shh solubilization from its lipidated terminal peptide anchors. This process, called shedding, converts tightly membrane-associated hydrophobic Shh precursors into delipidated soluble proteins. We show here that Disp-mediated Shh shedding is modulated by a serum factor that we identify as high-density lipoprotein (HDL). In addition to serving as soluble sinks for free membrane cholesterol, HDLs also accept the cholesterolmodified Shh peptide from Disp. The cholesteroylated Shh peptide is required and sufficient for Disp-mediated transfer because mCherry linked to cholesteroylated peptides associates with HDL in a Disp-dependent manner, but an N-palmitoylated Shh variant that lacks C-cholesterol does not. Disp-mediated Shh transfer to HDL is finalized by proteolytic processing of the palmitoylated N-terminal membrane anchor. Unlike dual processed soluble Shh with moderate bioactivity, HDL-associated N-processed Shh is highly bioactive. We suggest that the purpose of different post-translationally modified soluble Shh forms generated from one dual-lipidated cellular precursor is to fine-tune cellular responses in a tissue type-specific and time-specific manner

    Monocyte subpopulation profiling indicates CDK6-derived cell differentiation and identifies subpopulation-specific miRNA expression sets in acute and stable coronary artery disease

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    Coronary artery disease (CAD) is a long-lasting inflammatory disease characterized by monocyte migration into the vessel wall leading to clinical events like myocardial infarction (MI). However, the role of monocyte subsets, especially their miRNA-driven differentiation in this scenario is still in its infancy. Here, we characterized monocyte subsets in controls and disease phenotypes of CAD and MI patients using flow cytometry and miRNA and mRNA expression profiling using RNA sequencing. We observed major differences in the miRNA profiles between the classical (CD14++CD16−) and nonclassical (CD14+CD16++) monocyte subsets irrespective of the disease phenotype suggesting the Cyclin-dependent Kinase 6 (CDK6) to be an important player in monocyte maturation. Between control and MI patients, we found a set of miRNAs to be differentially expressed in the nonclassical monocytes and targeting CCND2 (Cyclin D2) that is able to enhance myocardial repair. Interestingly, miRNAs as miR-125b playing a role in vascular calcification were differentially expressed in the classical subset in patients suffering from CAD and not MI in comparison to control samples. In conclusion, our study describes specific peculiarities of monocyte subset miRNA expression in control and diseased samples and provides basis to further functional analysis and to identify new cardiovascular disease treatment targets

    Multilevel and empirical reliability estimates of learning growth: A simulation study and empirical illustration

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    Reliable learning progress information is crucial for teachers’ interpretation and data-based decision making in everyday classrooms. Slope estimates obtained from simple regression modeling or more complex latent growth models are typically used in this context as indicators of learning progress. Research on progress monitoring has used mainly two ways to estimate reliability of learning progress, namely (a) split-half reliability and (b) multilevel reliability. In this work we introduce empirical reliability as another attractive alternative to quantify measurement precision of slope estimates (and intercepts) in learning progress monitoring research. Specifically, we extended previous work on slope reliability in two ways: (a) We evaluated in a simulation study how well multilevel reliability and empirical reliability work as estimates of slope reliability, and (b) we wanted to better understand reliability of slopes as a latent variable (by means of empirical reliability) vs. slopes as an observed variable (by means of multilevel reliability). Our simulation study demonstrates that reliability estimation works well over a variety of different simulation conditions, while at the same time conditions were identified in which reliability estimation was biased (i.e., with very poor data quality, eight measurement points, and when empirical reliability was estimated). Furthermore, we employ multilevel reliability and empirical reliability to estimate reliability of intercepts (i.e., initial level) and slopes for the quop-L2 test. Multilevel and empirical reliability estimates were comparable in size with only slight advantages for latent variable scores. Future avenues for research and practice are discussed

    Respiration aligns perception with neural excitability

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    Recent studies from the field of interoception have highlighted the link between bodily and neural rhythms during action, perception, and cognition. The mechanisms underlying functional body-brain coupling, however, are poorly understood, as are the ways in which they modulate behavior. We acquired respiration and human magnetoencephalography data from a near-threshold spatial detection task to investigate the trivariate relationship between respiration, neural excitability, and performance. Respiration was found to significantly modulate perceptual sensitivity as well as posterior alpha power (8–13 Hz), a well-established proxy of cortical excitability. In turn, alpha suppression prior to detected versus undetected targets underscored the behavioral benefits of heightened excitability. Notably, respiration-locked excitability changes were maximized at a respiration phase lag of around –30° and thus temporally preceded performance changes. In line with interoceptive inference accounts, these results suggest that respiration actively aligns sampling of sensory information with transient cycles of heightened excitability to facilitate performance

    LIMB-Q Kids—German Translation and Cultural Adaptation

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    (1) Purpose: Lower limb deformities can have a severe impact on health-related quality of life (HRQL). LIMB-Q Kids is a new patient-reported outcome measure (PROM) aiming to elucidate the experience of 8–18-year-old patients before, during and after treatment, and to measure the different aspects of HRQL. The aim of this study was to translate and culturally adapt LIMB-Q Kids to German. (2) Methods: The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines were followed. Three forward translations, a backward translation, an expert panel meeting with eight participants, and twenty cognitive debriefing interviews led to the final German version of LIMB-Q Kids. (3) Results: In the forward translations, 4/159 items were difficult to translate, and 2/159 items in the backward translation differed from the original English version. Cognitive debriefing interviews with 20 patients identified 7/159 items that were difficult to comprehend/answer, and 2 of these items were changed. (4) Conclusions: Lower limb deformities can have a great impact on children, and it is important to measure and consider the impact on HRQL. In order to be able to use PROMs in different countries, conceptually equivalent translations and cultural adaptations should be performed in order to ensure comprehensibility. The final German version of LIMB-Q Kids is ready for use in an international field test

    Managing type 1 diabetes mellitus with a ketogenic diet

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    Summary: Traditional guidelines for type 1 diabetics do not restrict carbohydrates to improve clinical outcomes for patients. This paper highlights the favorable blood glucose control outcomes when a type 1 diabetic focuses on caloric intake from protein and healthy fats instead of the traditional carbohydrate-focused meals. We followed a male type 1 diabetic in his 20s adopting a ketogenic diet through a process of slowly lowering total daily carbohydrate intake. Diabetes-related biomarkers were measured throughout the process. Diabetes-related biomarkers saw massive improvements and ended up in the official non-diabetic range. Total daily insulin requirements dropped by 70%. The patient also experienced great improvements in his quality of life. This study demonstrates the possibility of improving diabetes-related biomarkers through dietary changes, which have positive effects on health outcomes in patients living with this disease

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