Novel Smooth Muscle Ca-Signaling Nanodomains in Blood Pressure Regulation.

Background: Ca signals in smooth muscle cells (SMCs) contribute to vascular resistance and control blood pressure. Increased vascular resistance in hypertension has been attributed to impaired SMC Ca signaling mechanisms. In this regard, transient receptor potential vanilloid 4 (TRPV4) ion channels are a crucial Ca entry pathway in SMCs.

Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension.

Recent studies have focused on the contribution of capillary endothelial TRPV4 channels to pulmonary pathologies, including lung edema and lung injury. However, in pulmonary hypertension (PH), small pulmonary arteries are the focus of the pathology, and endothelial TRPV4 channels in this crucial anatomy remain unexplored in PH. Here, we provide evidence that TRPV4 channels in endothelial cell caveolae maintain a low pulmonary arterial pressure under normal conditions.

Calcium Signal Profiles in Vascular Endothelium from Cdh5-GCaMP8 and Cx40-GCaMP2 Mice.

Introduction: Studies in Cx40-GCaMP2 mice, which express calcium biosensor GCaMP2 in the endothelium under connexin 40 promoter, have identified the unique properties of endothelial calcium signals. However, Cx40-GCaMP2 mouse is associated with a narrow dynamic range and lack of signal in the venous endothelium. Recent studies have proposed many GCaMPs (GCaMP5/6/7/8) with improved properties although their performance in endothelium-specific calcium studies is not known.

Epidemiology of Bloodstream Infections Caused by and That Are Piperacillin-Tazobactam-Nonsusceptible but Ceftriaxone-Susceptible.

Background: Piperacillin-tazobactam-nonsusceptible (TZP-NS) Enterobacteriaceae are typically also resistant to ceftriaxone. We recently encountered bacteremias due to () and () that were TZP-NS but ceftriaxone-susceptible (CRO-S).

Methods: We reviewed all and bacteremias from 2011 to 2015 at our center and assessed the prevalence, antimicrobial susceptibilities, genetic profiles, patient characteristics, treatments, and outcomes of TZP-NS/CRO-S infections.

Colonization With Levofloxacin-resistant Extended-spectrum β-Lactamase-producing Enterobacteriaceae and Risk of Bacteremia in Hematopoietic Stem Cell Transplant Recipients.

Background: Bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is associated with inadequate empirical therapy and substantial mortality in neutropenic patients. Strategies are needed to identify neutropenic patients at high risk of these infections.

Methods: From April 2014 to September 2016, we collected perianal swabs, both at admission and weekly thereafter, from patients undergoing hematopoietic stem cell transplantation (HSCT).

The growing threat of multidrug-resistant Gram-negative infections in patients with hematologic malignancies.

Prolonged neutropenia and chemotherapy-induced mucositis render patients with hematologic malignancies highly vulnerable to Gram-negative bacteremia. Unfortunately, multidrug-resistant (MDR) Gram-negative bacteria are increasingly encountered globally, and current guidelines for empirical antibiotic coverage in these patients may not adequately treat these bacteria. This expansion of resistance, coupled with traditional culturing techniques requiring 2-4 days for bacterial identification and antimicrobial susceptibility results, have grave implications for these immunocompromised hosts.

A review of antithrombotic therapy for transcatheter aortic valve replacement.

Aortic stenosis (AS) is a common valvular pathological finding in older adults. A latent period followed by rapid progression after the onset of symptoms can result in a high rate of death if left untreated. Aortic valve replacement (AVR) remains the standard of care for patients with severe symptomatic AS; however, due to comorbidities and age, patients may be ineligible for surgical AVR.

Synthesis of the WXYZA' domain of maitotoxin.

A synthesis of the WXYZA' domain (7) of the marine neurotoxin maitotoxin (1) is reported. The convergent synthetic strategy involves construction of key building blocks 11 and 12, their coupling, and the elaboration of the resulting ester (10) to the target molecule through a ring-closing metathesis and a hydroxy dithioketal cyclization as the key steps. For the construction of fragment 11, the Noyori reduction/Achmatowicz rearrangement and hydroxy epoxide opening technologies were applied (starting from furfuryl alcohol (13)), whereas for the synthesis of fragment 12, a carbohydrate-based approach was adopted (starting from 2-deoxy-D-ribose (14)).

Solid-phase approach to tetrahydroquinolones using a sulfur linker cleaved by SmI2.

[reaction: see text] A sulfur alpha-heteroatom-substituted carbonyl (HASC) linker has been utilized in a solid-phase approach to tetrahydroquinolones. The route illustrates the compatibility of the linker system with palladium-catalyzed transformations and its utility for library synthesis. The linker is cleaved by electron transfer from samarium(II) iodide.