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Staphylococcus aureus Biofilm-Associated Infections: Have We Found a Clinically Relevant Target?

Staphylococcus aureus is one of the most diverse bacterial pathogens. This is reflected in its ability to cause a wide array of infections and in genotypic and phenotypic differences between clinical isolates that extend beyond their antibiotic resistance status. Many S. aureus infections, including those involving indwelling medical devices, are therapeutically defined by the formation of a biofilm. This is reflected in the number of reports focusing on S. aureus biofilm formation and biofilm-associated infections. These infections are characterized by a level of intrinsic resistance that com

A Systematic Review of Trajectories of Clinically Relevant Distress Amongst Adults with Cancer: Course and Predictors.

To improve interventions for people with cancer who experience clinically relevant distress, it is important to understand how distress evolves over time and why. This review synthesizes the literature on trajectories of distress in adult patients with cancer. Databases were searched for longitudinal studies using a validated clinical tool to group patients into distress trajectories. Twelve studies were identified reporting trajectories of depression, anxiety, adjustment disorder or post-traumatic stress disorder. Heterogeneity between studies was high, including the timing of baseline assess

Skeletal parathyroid hormone hyporesponsiveness: a neglected, but clinically relevant reality in chronic kidney disease.

PURPOSE OF REVIEW: Defining the optimal parathyroid hormone (PTH) target in chronic kidney disease (CKD) is challenging, especially for bone outcomes, due to the substantial variability in the skeleton's response to PTH. Although PTH hyporesponsiveness is as integral a component of CKD-mineral bone disorder as elevated PTH levels, clinical awareness of this condition is limited. In this review, we will discuss factors and mechanisms contributing to PTH hyporesponsiveness in CKD. This knowledge may provide clues towards a personalized approach to treating secondary hyperparathyroidism in CKD.

A practical assessment protocol for clinically relevant P-glycoprotein-mediated drug-drug interactions.

BACKGROUND: Drug-drug interactions (DDIs) may influence the effectiveness and safety of medication treatment, which may require additional monitoring, dose adjustment or avoidance of certain drugs. DDIs involving P-glycoprotein (P-gp) affect many drugs, but current official product information is often insufficient to guide the management of these DDIs in clinical practice. The aim of this paper is to describe a protocol to assess DDIs involving P-gp and to develop and implement practice recommendations for clinically relevant P-gp-mediated DDIs that affect clinical outcomes through changes in

Cagrilintide is not associated with clinically relevant QTc prolongation: A thorough QT study in healthy participants.

AIMS: The combination of cagrilintide and semaglutide (CagriSema) is being developed for the treatment of obesity and type 2 diabetes. The objective of this thorough QT study was to confirm that cagrilintide does not result in a clinically relevant prolongation in cardiac repolarization compared with placebo. MATERIALS AND METHODS: This was a double-blind study (NCT05804162) in which healthy participants were randomized to cagrilintide, administered as a once-weekly subcutaneous injection dose escalated to 4.5 mg, or a placebo. The primary end point was the time-matched change from baseline i

Broth microdilution protocol for determining antimicrobial susceptibility of Legionella pneumophila to clinically relevant antimicrobials.

Currently there is no detailed, internationally agreed protocol defined to evaluate antimicrobial susceptibility testing (AST) for Legionella pneumophila (required to establish epidemiological cut-off value or "ECOFF" boundaries); therefore, antimicrobial resistance in these isolates cannot be defined. AST methods utilising media containing activated charcoal as an ingredient, to enable Legionella growth, are unreliable as noted in an internationally authored opinion paper and a new gold standard is required. Here we define a detailed protocol for broth microdilution (BMD) using defined cell c

Clinically relevant differences in spinal mobility related to daytime performance in patients with axial spondyloarthritis.

OBJECTIVE: Patients with axial spondyloarthritis (axSpA) suffer from clinical symptoms like morning stiffness and back pain. Mobility of patients with axSpA is often impaired. The aim of this study is to compare the performance of patients with axSpA regarding mobility measures including performance-based tests and objective electronic assessments with the Epionics SPINE device (ES) at different times of the day compared with healthy controls (HC). METHODS: Observational trial, consecutive inpatients with axSpA (n=100) and 20 HCs were examined in the morning (V1: before 10:00 am) and in the a

Clinically relevant differences between primary Raynaud's phenomenon and secondary to connective tissue disease.

OBJECTIVES: Raynaud's phenomenon (RP) is a symptom complex associated with digital vascular compromise. Our aim was to examine for clinically relevant differences between primary RP (PRP) and secondary RP (SRP) to connective tissue disease. METHODS: We report cross-sectional results from the Patient Survey of experiences of Raynaud's Phenomenon (PASRAP), which aimed to explore the broad-ranging impact of RP. The survey was widely distributed online including via social medial. Participation was voluntary and responses were anonymous. RESULTS: 1229 respondents completed PASRAP with self-repor

Normative vertebral deformity measurements in a clinically relevant population using magnetic resonance imaging.

BACKGROUND: Osteoporosis is the leading cause of vertebral fractures. Dual-energy X-ray absorptiometry (DXA) and radiographs are traditionally used to detect osteoporosis and vertebral fractures/deformities. Magnetic resonance imaging (MRI) can be utilized to detect the relative severity of vertebral deformities using three-dimensional information not available in traditional DXA and lateral two-dimensional radiography imaging techniques. AIM: To generate normative vertebral parameters in women using MRI and DXA scans, determine the correlations between MRI-calculated vertebral deformities an

Dexamethasone and concentrated growth factors on peripheral nerve injury: A clinic-relevant animal study.

BACKGROUND: Mandibular nerve injury is a common clinical condition that affects clinicians' management and patients' quality of life. In the literature, there are various effective treatments available. The primary purpose of this study was to determine and compare the effects of dexamethasone and concentrated growth factor (CGF) on regeneration in patients with nerve trauma that mimics clinical situations. METHODS: In this study, 36 rats were divided into 3 groups: the control, dexamethasone and CGF groups. The inferior alveolar nerve was traumatized through the extraction socket after mandi

The Clinical Relevance of the Lingual Branch in Ridge Augmentation of the Posterior Mandible: A Pilot Cadaver Study.

Guided bone regeneration (GBR) requires a tension-free flap without damaging the collateral circulation in order to secure better surgical outcomes. Topographic knowledge regarding the neurovascular bundles in the posterior aspect of the mandible can prevent complications during lingual flap design. The lingual branch (LB) of the inferior alveolar or maxillary arteries is not sufficiently illustrated or described in the literature. Nevertheless, it has an intimate relationship with the lingual nerve (LN) during ridge augmentation and implant-related posterior mandible surgery. Therefore, this

Prediction of clinically relevant postoperative pancreatic fistula using radiomic features and preoperative data.

Clinically relevant postoperative pancreatic fistula (CR-POPF) can significantly affect the treatment course and outcome in pancreatic cancer patients. Preoperative prediction of CR-POPF can aid the surgical decision-making process and lead to better perioperative management of patients. In this retrospective study of 108 pancreatic head resection patients, we present risk models for the prediction of CR-POPF that use combinations of preoperative computed tomography (CT)-based radiomic features, mesh-based volumes of annotated intra- and peripancreatic structures and preoperative clinical data

Effective and clinically relevant optimisation of cushioning stiffness to maximise the offloading capacity of diabetic footwear.

INTRODUCTION: Optimising the cushioning stiffness of diabetic footwear/orthoses can significantly enhance their offloading capacity. This study explores whether optimum cushioning stiffness can be predicted using simple demographic and anthropometric parameters. METHODS: Sixty-nine adults with diabetes and loss of protective sensation in their feet were recruited for this cross-sectional observational study. In-shoe plantar pressure was measured using Pedar® for a neutral diabetic shoe (baseline) and after adding cushioning footbeds of varying stiffness. The cushioning stiffness that achieved

Genomic analysis reveals HDAC1 regulates clinically relevant transcriptional programs in Pancreatic cancer.

Novel strategies are needed to combat multidrug resistance in pancreatic ductal adenocarcinoma (PDAC). We applied genomic approaches to understand mechanisms of resistance in order to better inform treatment and precision medicine. Altered function of chromatin remodeling complexes contribute to chemoresistance. Our study generates and analyzes genomic and biochemical data from PDAC cells overexpressing HDAC1, a histone deacetylase involved in several chromatin remodeling complexes. We characterized the impact of overexpression on drug response, gene expression, HDAC1 binding, and chromatin st

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… We highlight the clinical relevance of this approach by using the data to nominate a novel nine gene signature that predicts HDAC1 expression and is associated with patient survival. … To determine the clinical relevance of the genes selected using the LASSO model, survival analysis was performed comparing the patients in the top and bottom quartile of predictor values from the regression and the patients group with the highest predictor values had significantly worse overall survival …

Altered chronic glycemic control in a clinically relevant model of rat thoracic spinal contusion.

The lifetime risk for Type 2 diabetes mellitus remains higher in people with spinal cord injuries (SCIs) than in the able-bodied population. However, the mechanisms driving this disparity remain poorly understood. The goal of the present study was to evaluate the impact of a palatable high-fat diet (HFD) on glycemic regulation using a rodent model of moderate thoracic contusion. Animals were placed on either Chow or HFD and tolerance to glucose, insulin, and ENSURE mixed meal were investigated. Important targets in the gut-brain axis were investigated. HFD consumption equally induced weight ga

Complications of Synthetic Midurethral Slings: Is There a Relevant Discrepancy Between Observational Data and Clinical Trials?

CONTEXT: The complications of synthetic midurethral slings (MUSs) in women with stress urinary incontinence (SUI) have become a globally debated issue. OBJECTIVE: To systematically review the short- and long-term complications of mesh slings reported in observational data compared with clinical trial data, to determine whether the complication rates from clinical trials reflects "real-world" observational data. EVIDENCE ACQUISITION: PubMed and Cochrane Library were searched. Methods as detailed in Preferred Reporting Items for Systematic Reviews and Meta-analyses and Cochrane Handbook for Sy

Cross-sectional study evaluating the association of haemophilia-related distress and clinically relevant outcomes.

INTRODUCTION: In chronic diseases, disease-related distress can impact disease outcomes. Distress and haemophilia-related distress has been demonstrated in people with haemophilia (PwH). The association of haemophilia-related distress on disease outcomes among PwH is unknown. AIM: To study the association of haemophilia-related distress with haemophilia specific outcomes, including adherence to prophylactic therapy, the presence of a target joint, healthcare utilization and work-impairment. METHODS: In a cross-sectional study, adults with haemophilia A or B were enrolled in a study to valida

Rapid Diagnostic Tests for the Detection of the Four Dengue Virus Serotypes in Clinically Relevant Matrices.

The efficient and accurate diagnosis of dengue, a major mosquito-borne disease, is of primary importance for clinical care, surveillance, and outbreak control. The identification of specific dengue virus serotype 1 (DENV-1) to DENV-4 can help in understanding the transmission dynamics and spread of dengue disease. The four rapid low-resource serotype-specific dengue tests use a simple sample preparation reagent followed by reverse transcription-isothermal recombinase polymerase amplification (RT-RPA) combined with lateral flow detection (LFD) technology. Results are obtained directly from clin

A clinically relevant model of focal embolic cerebral ischemia by thrombus and thrombolysis in rhesus monkeys.

Over decades of research into the treatment of stroke, nearly all attempts to translate experimental treatments from discovery in cells and rodents to use in humans have failed. The prevailing belief is that it might be necessary to pretest pharmacological neuroprotection in higher-order brains, especially those of nonhuman primates (NHPs). Over the past few years, chemical thrombolysis and mechanical thrombectomy have been established as the standard of care for ischemic stroke in patients. The spotlight is now shifting towards emphasizing both focal ischemia and subsequent reperfusion in dev

Analyses on Clinical Efficacy of TIPS in the Treatment of Cirrhotic Portal Hypertension and Relevant Influencing Factors.

The study aimed to explore the clinical efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in treating cirrhotic portal hypertension and relevant influencing factors. 100 patients with cirrhotic portal hypertension receiving TIPS in the 980 hospitals of PLA logistic force from January 2015 to January 2018 were enrolled. Blood was collected from patients to detect liver function indicators [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], renal function indicators [blood urea nitrogen (BUN) and creatinine (Cr)], glucose metabolism indicators [insulin and gluco