Challenges and perspectives of CRISPR-based technology for diagnostic applications

The precision and versatility of CRISPR-based techniques, combined with the advantages of nucleic acid-based nanotechnology, hold great promise in transforming the landscape of molecular diagnostics. While significant progress has been made, current CRISPR-based platforms primarly focus on nucleic acid detection. To expand the applicability and fully leverage the advantages offered by CRISPR-based diagnostics, ongoing efforts explore molecular strategies to develop CRISPR sensors capable of detecting a diverse range of analytes beyond nucleic acids. In addition, challenges still persist in the adaptation of CRISPR platforms for point-of-care (POC) applications, involving concerns such as portability and automation, as well as the complexities associated with multiplexing. Here, we provide a detailed classification and comprehensive discussion of molecular strategies facilitating the conversion of non-nucleic acid target binding into CRISPR-powered outputs with an emphasis on their corresponding design principles. Furthermore, the second part of the review outlines current challenges and potential solutions for seamlessly integrating these strategies into user-friendly platforms and rapid tests specifically tailored for point-of-care (POC)

are drug eluting stents superior to bare metal stents in patients with unprotected non bifurcational left main disease insights from a multicentre registry

Aims To compare long-term clinical outcome following drug-eluting stents (DES) or bare-metal stents (BMS) implantation on lesions located at the ostium or the shaft of the left main in a large real-world population. The advent of DES decreased the risk of unprotected left main coronary artery (ULMCA) restenosis when compared with BMS, but it is unclear if this advantage continues when non-bifurcational lesions are considered. Methods and results The GISE-SICI registry is a retrospective, observational multicentre registry promoted by the Italian Society of Invasive Cardiology in which 19 high-volume participating centres enrolled 1453 consecutive patients who underwent percutaneous coronary intervention on ULMCA between January 2002 and December 2006. From the registry, a total of 479 consecutive patients with ostial and shaft lesions who underwent DES ( n = 334) or BMS ( n = 145) implantation were analysed with extensive multivariable and propensity score adjustments. At 3-year follow-up, risk-adjusted survival rates were higher in patients treated with DES than in those treated with BMS. The adjusted hazard ratio (HR) for the risk of mortality after DES implantation relative to BMS implantation was 0.37 (95% CI: 0.15–0.96, P = 0.04). The adjusted HR for the risk of cardiac mortality was 0.31 (95% CI: 0.09–1.04, P = 0.06). The adjusted 3-year rates of target lesion revascularization (TLR) were not significantly lower in the DES group than in the BMS group ( P = 0.60). Conclusion In a large population of patients with lesions located at the ostium or the shaft of the left main in a real-world setting, DES were associated with favourable clinical outcomes when compared with BMS, although there was no evidence of a significant reduction in TLR with DES vs. BMS

Presymptomatic geographical distribution of ALS patients suggests the involvement of environmental factors in the disease pathogenesis

BackgroundGiven that the pathogenetic process of ALS begins many years prior to its clinical onset, examining patients' residential histories may offer insights on the disease risk factors. Here, we analyzed the spatial distribution of a large ALS cohort in the 50 years preceding the disease onset.MethodsData from the PARALS register were used. A spatial cluster analysis was performed at the time of disease onset and at 1-year intervals up to 50 years prior to that.ResultsA total of 1124 patients were included. The analysis revealed a higher-incidence cluster in a large area (435,000 inhabitants) west of Turin. From 9 to 2 years before their onset, 105 cases were expected and 150 were observed, resulting in a relative risk of 1.49 (P = 0.04). We also found a surprising high number of patients pairs (51) and trios (3) who lived in the same dwelling while not being related. Noticeably, these occurrences were not observed in large dwellings as we would have expected. The probability of this occurring in smaller buildings only by chance was very low (P = 0.01 and P = 0.04 for pairs and trios, respectively).ConclusionsWe identified a higher-incidence ALS cluster in the years preceding the disease onset. The cluster area being densely populated, many exposures could have contributed to the high incidence ALS cluster, while we could not find a shared exposure among the dwellings where multiple patients had lived. However, these findings support that exogenous factors are likely involved in the ALS pathogenesis

The Efficacy of a New AMCOP® Elastodontic Protocol for Orthodontic Interceptive Treatment: A Case Series and Literature Overview

Background: Elastodontics is a specific interceptive orthodontic treatment that uses removable elastomeric appliances. They are functional appliances that produce neuromuscular, orthopedic and dental effects. Thus, these devices are useful in the developmental age, when skeletal structures are characterized by important plasticity and adaptation capacity, allowing to remove factors responsible for malocclusions. Elastomeric devices are generally well tolerated by patients requiring simple collaboration and management. This work can be useful to update all orthodontists already adopting these appliances or for those who want to approach them for the first time. This study aimed to describe four cases treated with new elastomeric devices called AMCOP Bio-Activators and to provide an overview of elastodontics, its evolution, indications and limits. Methods: A total of four clinical cases were presented after a treatment period of 16–20 months to evaluate the clinical and radiological effects of the elastodontic therapy. Results: The effectiveness of Bio-Activators on clinical cases was evidenced with a significant improvement in skeletal and dentoalveolar relationship, and malocclusion correction in a limited treatment period (16–20 months). Conclusions: The Bio-Activators showed clinical effectiveness to achieve therapeutic targets according to a low impact on the patient’s compliance

Spinal cord stimulation in the treatment of refractory angina: systematic review and meta-analysis of randomised controlled trials

<p>Abstract</p> <p>Background</p> <p>The aim of this paper was undertake a systematic review and meta-analysis of the use of spinal cord stimulation (SCS) in the management of refractory angina.</p> <p>Methods</p> <p>We searched a number of electronic databases including Medline, Embase and Cochrane Library up to February 2008 to identify randomised controlled trials (RCTs) reporting exercise capacity, ischemic burden, functional class, quality of life, usage of anti-anginal medication, costs and adverse events including mortality. Results were reported both descriptively for each study and using random effects meta-analysis. Given the variety in outcomes reported, some outcome results were pooled as standardised mean differences (SMD) and reported in standard deviation units.</p> <p>Results</p> <p>Seven RCTs were identified in a total of 270 refractory angina patients. The outcomes of SCS were found to be similar when directly compared to coronary artery bypass grafting (CABG) and percutaneous myocardial laser revascularisation (PMR). Compared to a 'no stimulation' control, there was some evidence of improvement in all outcomes following SCS implantation with significant gains observed in pooled exercise capacity (SMD: 0.76, 0.07 to 1.46, <it>p </it>= 0.03) and health-related quality of life (SMD: 0.83, 95% CI: 0.32 to 1.34, <it>p </it>= 0.001). Trials were small and were judged to range considerably in their quality. The healthcare costs of SCS appeared to be lower than CABG at 2-years follow up.</p> <p>Conclusion</p> <p>SCS appears to be an effective and safe treatment option in the management of refractory angina patients and of similar efficacy and safety to PMR, a potential alternative treatment. Further high quality RCT and cost effectiveness evidence is needed before SCS can be accepted as a routine treatment for refractory angina.</p