Antibiotic resistance is an emerging threat to global health. Current treatment regimens for these types of bacterial infections are becoming increasingly inadequate. Thus, new innovative technologies are needed to help identify and characterize novel drugs and drug targets which are critical in order to combat multidrug-resistant bacterial strains. Bacterial efflux systems have emerged as an attractive target for drug design, as blocking their export function significantly increases the potency of administered antibiotics. However, in order to develop potent and tolerable efflux pump inhibitors with high efficacy, detailed structural information is required for both the apo- and substrate-bound forms of these membrane proteins. The emergence of cryo-electron microscopy (cryo-EM) has greatly advanced the field of membrane protein structural biology. It has significantly enhanced the ability to solve large multi-protein complexes as well as extract meaningful data from a heterogeneous sample, such as identification of several assembly states of the bacterial ribosome, from a single data set. This technique can be expanded to solve the structures of substrate-bound efflux pumps and entire efflux systems from previously unusable membrane protein sample preparations. Subsequently, cryo-EM combined with other biophysical techniques has the potential to markedly advance the field of membrane protein structural biology. The ability to discern complete transport machineries, enzymatic signal transduction pathways, and other membrane-associated complexes will help us fully understand the complexities of the membrane proteome.Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease affecting the joints and other organs that occurs in 1 in 1,000 children in the United States. Given the various categories of JIA, interpretation of the literature can be difficult. In this review, new developments in understanding non-systemic JIA and its treatment will be covered. Recent advances in the journey toward personalized treatment in JIA will be highlighted, including a review of currently available biologic modifiers. Uveitis and the temporomandibular joint will be discussed as particularly challenging treatment issues. Recent guideline updates and literature-guided treatment decisions will be reviewed.The therapeutic landscape of chronic lymphocytic leukemia (CLL) underwent a paradigm shift in 2014 with the approval of ibrutinib, which binds covalently to the C481 residue of Bruton's tyrosine kinase (BTK) and irreversibly inhibits it. A number of large, phase 3 trials conducted in both the frontline and the relapsed/refractory settings resulted in the approval of ibrutinib for all CLL. Indeed, the role of chemoimmunotherapy in CLL is fast dwindling. The limitations of ibrutinib, e.g. the development of resistance-conferring C481 BTK mutations and the toxicity issues of atrial fibrillation and bleeding, in particular, have also become apparent with longer-term follow-up. This has spurred the development of second-generation, irreversible inhibitors with greater selectivity for BTK and third-generation, reversible BTK inhibitors to address C481 site mutations. The last 3 years have also witnessed enormous growth in the therapeutic role of the B-cell lymphoma 2 (BCL-2) antagonist venetoclax, initially approved (in 2016) only for patients with relapsed, 17p-deleted CLL. Venetoclax, in combination with CD20 antibodies, is currently approved for both treatment-naïve and relapsed/refractory patients, regardless of genomic subtype. Robust results have also been reported for ibrutinib plus venetoclax, and "triple" combinations of a BTK inhibitor, venetoclax, and obinutuzumab are now being pursued. The major questions facing the field at present are how best to select patients for BTK inhibitor monotherapy versus venetoclax/obinutuzumab upfront, what to do after failure of both BTK inhibitor(s) and venetoclax, and the ideal way to integrate measurable residual disease data into decisions regarding treatment choice, duration, and discontinuation.Organ transplantation is a life-saving treatment for end-stage organ failure. However, despite advances in immunosuppression, donor matching, tissue typing, and organ preservation, many organs are still lost each year to rejection. Ultimately, tolerance in the absence of immunosuppression is the goal, and although this seldom occurs spontaneously, a deeper understanding of alloimmunity may provide avenues for future therapies which aid in its establishment. Here, we highlight the recent key advances in our understanding of the allograft response. On the innate side, recent work has highlighted the previously unrecognised role of innate lymphoid cells as well as natural killer cells in promoting the alloresponse. The two major routes of allorecognition have recently been joined by a third newly identified pathway, semi-direct allorecognition, which is proving to be a key active pathway in transplantation. Through this review, we detail these newly defined areas in the allograft response and highlight areas for potential future therapeutic intervention.The incidence of thrombotic disorders in neonates and children is increasing with advances in diagnostic modalities, supportive care, and management of many health conditions.  https://www.selleckchem.com/products/icec0942-hydrochloride.html  The developing coagulation system, need for intensive care, including catheterization, and co-morbid conditions are responsible for the relatively high risk of thrombosis in neonates compared to older children. This review addresses the advances over the last 3 years in neonatal thrombosis, with a focus on epidemiology, cerebral sinovenous thrombosis (CSVT), renal vein thrombosis (RVT), and portal vein thrombosis (PVT). The incidence of neonatal thrombosis in the contemporary era is reported to be 6.9-15 per 1,000 neonatal intensive care unit (NICU) admissions, compared to 2.4 per 1,000 NICU admissions reported in older registry data. The majority of recently published studies are small, retrospective, and from single centers, albeit they emphasize the need for definitive data to support the efficacy and safety of anticoagulation therapy (ACT) in the management of CSVT, RVT, and PVT.