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Aimed towards senescent cells boosts functional healing soon after spinal cord injury.
The emergence and spread of extended-spectrum β-lactamases (ESBLs), metallo-β-lactamases (MBLs), or variant low-affinity penicillin-binding proteins (PBPs) pose a major threat to our ability to treat bacterial infection using β-lactam antibiotics. Although combinations of β-lactamase inhibitors with β-lactam agents have been clinically successful, there are no MBL inhibitors in current therapeutic use. Furthermore, recent clinical use of new-generation cephalosporins targeting PBP2a, an altered PBP, has led to the emergence of resistance to these antimicrobial agents. Previous work shows that natural polyphenols such as cranberry-extracted proanthocyanidins (cPAC) can potentiate non-β-lactam antibiotics against Gram-negative bacteria. selleckchem This study extends beyond previous work by investigating the in vitro effect of cPAC in overcoming ESBL-, MBL-, and PBP2a-mediated β-lactam resistance. The results show that cPAC exhibit variable potentiation of different β-lactams against β-lactam-resistant Enterobacteriaceae cs by interfering with two different resistance mechanisms. By their broad-spectrum inhibitory ability, cranberry-extracted proanthocyanidins could have the potential to enhance the effectiveness of existing β-lactam agents.Transcriptional enhancers are critical for development and phenotype evolution and are often mutated in disease contexts; however, even in well-studied cell types, the sequence code conferring enhancer activity remains unknown. To examine the enhancer regulatory code for pluripotent stem cells, we identified genomic regions with conserved binding of multiple transcription factors in mouse and human embryonic stem cells (ESCs). Examination of these regions revealed that they contain on average 12.6 conserved transcription factor binding site (TFBS) sequences. Enriched TFBSs are a diverse repertoire of 70 different sequences representing the binding sequences of both known and novel ESC regulators. Using a diverse set of TFBSs from this repertoire was sufficient to construct short synthetic enhancers with activity comparable to native enhancers. Site-directed mutagenesis of conserved TFBSs in endogenous enhancers or TFBS deletion from synthetic sequences revealed a requirement for 10 or more different TFBSs. Furthermore, specific TFBSs, including the POU5F1SOX2 comotif, are dispensable, despite cobinding the POU5F1 (also known as OCT4), SOX2, and NANOG master regulators of pluripotency. These findings reveal that a TFBS sequence diversity threshold overrides the need for optimized regulatory grammar and individual TFBSs that recruit specific master regulators.The efficacy of digital contact tracing against coronavirus disease 2019 (COVID-19) epidemic is debated Smartphone penetration is limited in many countries, with low coverage among the elderly, the most vulnerable to COVID-19. We developed an agent-based model to precise the impact of digital contact tracing and household isolation on COVID-19 transmission. The model, calibrated on French population, integrates demographic, contact and epidemiological information to describe exposure and transmission of COVID-19. We explored realistic levels of case detection, app adoption, population immunity, and transmissibility. Assuming a reproductive ratio R = 2.6 and 50% detection of clinical cases, a ~20% app adoption reduces peak incidence by ~35%. With R = 1.7, >30% app adoption lowers the epidemic to manageable levels. Higher coverage among adults, playing a central role in COVID-19 transmission, yields an indirect benefit for the elderly. These results may inform the inclusion of digital contact tracing within a COVID-19 response plan.This position paper was intended to update the former consensus between the French Societies of Radiology and Cardiology about the use of stress cardiac magnetic resonance imaging (MRI) in chronic coronary syndrome published in 2009. The Delphi method was used to build the present consensus. This expert panel consensus includes recommendations for indications, procedure with patient preparation, stress inducing drugs, acquisition protocol, interpretation and risk stratification by stress MRI.Effective and safe surgery results from a complex sociotechnical process prone to human error. Acquiring large amount of data on surgical care and modelling the process of surgery with artificial intelligence's computational methods could shed lights on system strengths and limitations and enable computer-based smart assistance. With this vision in mind, surgeons and computer scientists have joined forces in a novel discipline called Surgical Data Science. In this regard, operating room (OR) black boxes and surgical control towers are being developed to systematically capture comprehensive data on surgical procedures and to oversee and assist during operating rooms activities, respectively. Most of the early Surgical Data Science works have focused on understanding risks and resilience factors affecting surgical safety, the context and workflow of procedures, and team behaviors. These pioneering efforts in sensing and analyzing surgical activities, together with the advent of precise robotic actuators, bring surgery on the verge of a fourth revolution characterized by smart assistance in perceptual, cognitive and physical tasks. Barriers to implement this vision exist, but the surgical-technical partnerships set by ambitious efforts such as the OR black box and the surgical control tower are working to overcome these roadblocks and translate the vision and early works described in the manuscript into value for patients, surgeons and health systems.Removal of cement and especially the distal cement plug during cemented arthroplasty replacements is key to the success of the surgery, but can be challenging for the surgeon. The methods employed for this step can be very varied, ranging from removal with the aid of rasps, drills, ultrasonic techniques, to bone windows for direct access to the plug. These techniques can sometimes lead to perforation of the bone cortex and even to the production of uncontrolled fractures that prevent safe implantation of the new implant. The aim of this study is to review the different cement removal techniques and to evaluate the efficacy of a new technique, which allows the cement plug to be removed in a safe and controlled manner, avoiding the need for osteotomies. A customised guide is used for this purpose. This allows an effective and leak-free re-cementing of the new implants. We present 3 cases of distal cement removal using a customised guide that allows the cement plug to be broached. In all 3 cases, after cement removal, the implantation of longer stems with correct cementation was achieved.
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