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The use of nanoparticles (NPs) in biomedicine has made a gradual transition from proof-of-concept to clinical applications, with several NP types meeting regulatory approval or undergoing clinical trials. A new type of metallic nanostructures called ultrasmall nanoparticles (usNPs) and nanoclusters (NCs), while retaining essential properties of the larger (classical) NPs, have features common to bioactive proteins. This combination expands the potential use of usNPs and NCs to areas of diagnosis and therapy traditionally reserved for small-molecule medicine. Their distinctive physicochemical properties can lead to unique in vivo behaviors, including improved renal clearance and tumor distribution. Both the beneficial and potentially deleterious outcomes (cytotoxicity, inflammation) can, in principle, be controlled through a judicious choice of the nanocore shape and size, as well as the chemical ligands attached to the surface. At present, the ability to control the behavior of usNPs is limited, partly because advances are still needed in nanoengineering and chemical synthesis to manufacture and characterize ultrasmall nanostructures and partly because our understanding of their interactions in biological environments is incomplete. This review addresses the second limitation. We review experimental and computational methods currently available to understand molecular mechanisms, with particular attention to usNP-protein complexation, and highlight areas where further progress is needed. Fezolinetant purchase We discuss approaches that we find most promising to provide relevant molecular-level insight for designing usNPs with specific behaviors and pave the way to translational applications.Background Research site monitoring (RSM) is an effective way to ensure compliance with Good Clinical Practice (GCP). However, RSM is not offered to trainees (investigators) at African Institutions routinely. The Makerere University/Uganda Virus Research Institute Centre of Excellence in Infection and Immunity Research and Training (MUII-Plus) introduced internal monitoring to promote the quality of trainees' research projects. Here, we share our monitoring model, experiences and achievements, and challenges encountered. Methods We analysed investigators' project reports from monitoring visits undertaken from April 2017 to December 2019. Monitors followed a standard checklist to review investigator site files and record forms, and toured site facilities. We planned four monitoring visits for each trainee one at site initiation, two interim, and a closeout monitoring visit. A team of two monitors conducted the visits. Results We monitored 25 out of the 26 research projects in progress between April 2017 and Deal higher degrees and research ethics committees should enforce this as a requirement for project approvals.Cellular adaptation to stress and metabolic cues requires a coordinated response of different intracellular compartments, separated by semipermeable membranes. One way to facilitate interorganellar communication is via membrane contact sites, physical bridges between opposing organellar membranes formed by an array of tethering machineries. These contact sites are highly dynamic and establish an interconnected organellar network able to quickly respond to external and internal stress by changing size, abundance and molecular architecture. Here, we discuss recent work on nucleus-vacuole junctions, connecting yeast vacuoles with the nucleus. Appearing as small, single foci in mitotic cells, these contacts expand into one enlarged patch upon nutrient exhaustion and entry into quiescence or can be shaped into multiple large foci essential to sustain viability upon proteostatic stress at the nuclear envelope. We highlight the remarkable plasticity and rapid remodelling of these contact sites upon metabolic or proteostatic stress and their emerging importance for cellular fitness.

Despite improvement in available tools and techniques, procedural complications like coronary perforation can occur during percutaneous coronary intervention (PCI). Severe proximal coronary perforations are usually caused by balloon and vessel size mismatch but can also occur with appropriately sized balloons or stents if the coronary vessel has very eccentric calcification or if there is negative remodelling of the vessel.

A 74-year-old man with a history of type II diabetes mellitus, hypertension, and chronic coronary syndrome (previous PCI 10 years before) presented with unstable angina of 2 weeks of duration. Coronary angiography revealed a patent stent in left anterior descending artery, significant disease in left circumflex artery and diffuse calcified lesion in dominant right coronary artery (RCA). During angioplasty of RCA, the patient developed severe Ellis grade III perforation, which was successfully managed with modified double guiding catheter 'Ping Pong' technique. In this technique, the already engaged 7 French (F) Amplatz Left 1 guide catheter was used to deliver the bulky covered stent in highly tortuous and calcified RCA while a second 6F guide catheter (Judkin Right) introduced through contralateral femoral access was used for introducing the balloon, which initially sealed the perforation and subsequently acted as a distal anchor to provide strong support to deliver the covered stent.

In a case of severe coronary perforation, modified Ping Pong technique using a small-sized second guide catheter complimentary to the first guide catheter, can be used to deploy bulky covered stent.

In a case of severe coronary perforation, modified Ping Pong technique using a small-sized second guide catheter complimentary to the first guide catheter, can be used to deploy bulky covered stent.

Primary cardiac lymphoma (PCL) is rare and can present with a wide variety of clinical symptoms, frequently leading to a delay in diagnosis.

We report a case of a PCL in an 81-year-old man. Cardiac magnetic resonance imaging showed multiple masses in the right atrium and a mass in the right ventricular outflow tract extending to the pulmonary artery. Biopsy revealed a diffuse large B-cell lymphoma. The patient also had metastases to the liver and lung on the positron emission tomography-computed tomography (PET-CT) scan. He was treated with R-CHOP chemotherapy, with complete remission documented PET-CT scans.

Although most patients with PCL die before chemotherapy can be initiated, a timely diagnosis can result in a favourable outcome.

Although most patients with PCL die before chemotherapy can be initiated, a timely diagnosis can result in a favourable outcome.

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