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rget sites for ANG II in adult human and rodent kidneys.Mass spectrometry-based proteomics profiling is a discovery tool that enables researchers to understand the mechanisms of action of drug candidates. When applied to proteolysis targeting chimeras (PROTACs) such approaches provide unbiased perspectives of the binding, degradation selectivity, and mechanism related to efficacy and safety. Ebselen Specifically, global profiling experiments can identify direct degradation events and assess downstream pathway modulation that may result from degradation or off-target inhibition. Targeted proteomics approaches can be used to quantify the levels of relevant E3 ligases and the protein of interest in cell lines and tissues of interest, which can inform the line of sight and provide insights on possible safety liabilities early in the project. Furthermore, proteomics approaches can be applied to understand protein turnover and resynthesis rates and inform on target tractability, as well as pharmacokinetics/pharmacodynamics understanding. In this perspective, we survey the literature around the impact of mass spectrometry-based proteomics in the development of PROTACs and present our envisioned proteomics cascade for supporting targeted protein degradation projects.The Covid-19 pandemic in the UK has been greatly worsened by the mutation of the virus, which began in the South East and was rapidly spreading and in danger of overwhelming the NHS as hospital admissions and deaths continued to rise. In consequence, the Chief Medical Officers of all four nations supported the UK government's sudden decision to delay the second dose of the Pfizer/BioNtech and Oxford/AstraZeneka vaccines for 12 weeks (instead of 3) so that more people in the most vulnerable population groups would receive a first dose and some immunity sooner. The expectation is that this strategy would reduce hospital admissions and deaths. This article considers key medical and legal issues arising from this decision and discusses inter alia rationing of scarce resources, fairness, whether it is for the greater good, consent, individual human rights, negligence and claims for potential or actual injury.

Many of the potential barriers to providing telehealth services already disproportionately impact vulnerable populations. The purpose of this study was to assess the incorporation of synchronous ophthalmology telemedicine visits in a tertiary university-based ophthalmology clinic for low-income and uninsured patients in the COVID-19 era.

The records of 18 patients who were due for an in-person visit in the medically underserved patient clinic at our institute were reviewed. Patients considered high risk of ocular morbidity progression were approved to proceed with an in-person visit. Patients with non-urgent visit indications were attempted to be contacted by telephone to be offered a telemedicine telephone visit as an alternative to a postponed in-person office visit.

Clinical triage by an attending ophthalmologist determined that 17 patients (94.4%, n = 18) had visit indications appropriate for evaluation by telemedicine. Six patients (35.3%, n = 17) were successfully contacted and offered a telemedicthis population was the ability to successfully contact patients to offer and schedule these visits.The onset of the COVID-19 pandemic and subsequent county shelter-in-place order forced the Cardinal Free Clinics (CFCs), Stanford University's 2 student-run free clinics, to close in March 2020. As student-run free clinics adhering to university-guided COVID policies, we have not been able to see patients in person since March of 2020. However, the closure of our in-person operations provided our student management team with an opportunity to innovate. In consultation with Stanford's Telehealth team and educators, we rapidly developed a telehealth clinic model for our patients. We adapted available telehealth guidelines to meet our patient care needs and educational objectives, which manifested in 3 key innovations reconfigured clinic operations, an evidence-based social needs screen to more effectively assess and address social needs alongside medical needs, and a new telehealth training module for student volunteers. After 6 months of piloting our telehealth services, we believe that these changes have made our services and operations more robust and provided benefit to both our patients and volunteers. Despite an uncertain and evolving public health landscape, we are confident that these developments will strengthen the future operations of the CFCs.

Aberrant right subclavian artery (ARSA) associated with Kommerell's diverticulum (KD) is a common congenital arch anomaly. It can be complicated by type B aortic dissection (TBAD) or aneurysmal formation at its ostium. Recently, hybrid repair with thoracic endovascular aortic repair (TEVAR) has appeared to be more favorable. Due to the normal anatomic proximity of the ARSA to the left subclavian artery (LSA) orifice in KD, coverage of the bilateral subclavian arteries (SCAs) to obtain an adequate proximal landing zone (PLZ) is usually required, and double cervicotomy for SCA revascularization potentially increases the risk of complications.

This technique was demonstrated on a 50-year-old man presenting with progressive aneurysmal formation of KD with ARSA after chronic TBAD. A 3-step technique, namely left cervical debranching with a left common carotid artery to LSA bypass graft, TEVAR, and an LSA-to-ARSA endovascular debranching with a self-expanding covered stent by a through-and-through wire from the right brachial artery to the bypass graft, was performed in a 1-stage repair to cover the primary tear of TBAD and preserve the bilateral SCAs. The postoperative course was uneventful.

This technique can prevent complications from double cervicotomy and achieve an adequate PLZ with preservation of the bilateral SCAs for TEVAR.

This technique can prevent complications from double cervicotomy and achieve an adequate PLZ with preservation of the bilateral SCAs for TEVAR.Current clinical guidelines for heart failure (HF) contain a brand new therapeutic strategy for HF with reduced ejection fraction (HFrEF), which is based on neurohumoral modulation through the use of angiotensin receptor neprilysin inhibitors. There is a large body of evidence for the fact that sodium-glucose co-transporter 2 inhibitors may significantly improve all-cause mortality, cardiovascular mortality and hospitalization for HF in patients with HFrEF who received renin-angiotensin system blockers including angiotensin receptor neprilysin inhibitors, β-blockers and mineralocorticoid receptor antagonists. The review discusses that sodium-glucose co-transporter 2 inhibitors have a wide spectrum of favorable molecular effects and contribute to tissue protection, improving survival in HFrEF patients.