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patients. Further studies in larger study populations are required to verify these results.BACKGROUND Use of direct-acting oral anticoagulants for patients with nonvalvular atrial fibrillation (NVAF) in skilled nursing facilities (SNFs) is increasing. Rivaroxaban is commonly used in this setting as an alternative to warfarin, based on comparable or increased efficacy in preventing stroke and a similar or lower risk of major bleeding. OBJECTIVE The aim of this study was to compare healthcare resource utilization (HCRU) and costs between NVAF patients receiving rivaroxaban or warfarin in SNFs. METHODS This retrospective study examined de-identified claims from Optum® Clinformatics® Extended Data Mart (1 January 2013-31 December 2017). Eligible patients had an AF diagnosis, were prescribed rivaroxaban or warfarin during an SNF stay, and had one or more&nbsp;such prescriptions filled in the 6&nbsp;months preceding the stay. Patients were excluded if they received another oral anticoagulant or had evidence of valvular heart disease, mitral stenosis, or organ/tissue transplant. HCRU, mean number of events, and allre lower among patients with NVAF who were experienced users of rivaroxaban compared with those who were experienced users of warfarin. These findings may help inform clinical decision making to reduce the economic burden of NVAF among older adults in SNFs.BACKGROUND Proton pump inhibitors (PPIs) are widely used in the general population often without an endpoint. The practice of prescribing PPIs in the hemodialysis (HD) population is unknown. Thus, we aimed to identify the practice pattern related to PPI prescription for HD patients in Japan through a questionnaire survey. METHODS We conducted a questionnaire survey for physicians engaged in dialysis practice through email. An email was sent to physicians listed in the Japanese Society of Nephrology (JSN) and iHOPE International registry. RESULTS We received 187 physicians' answers. One-hundred twelve (60%) physicians would prefer to continuously prescribe PPIs after 8&nbsp;weeks of treatment for peptic ulcer (PU) or gastroesophageal reflux disease (GERD). The main reason for continuous PPI prescription was the concern for recurrence of PU or GERD. Approximately 20% of physicians responded that they were not accustomed to de-prescribing PPIs for PU or GERD. The reason for PPI de-prescription was the concern for side effects or insurance adaptation period. Even in cases wherein PPIs were prescribed for uncertain reasons, 42% physicians would continuously prescribe PPIs. Most physicians (82%) who answered about stopping PPIs regarded HD patients as a high-risk group for PU. CONCLUSIONS PPI prescription is often continued in HD patients. [https://www.selleckchem.com/products/c188-9.html TTI 101 research buy] De-prescription is not a common practice in Japan. It remains unclear whether discontinuation of PPIs should be recommended in hemodialysis patients who have a high risk of gastrointestinal ulcer. Yet, considering the side effects and polypharmacy in the HD population, more discussions on preferable de-prescription of PPIs are needed.Grizzly bears (Ursus arctos) appear to be attracted to natural and anthropogenic forage along railways, which may increase collision vulnerability, but also potentially causes exposure to contaminants associated with railway infrastructure. We assessed contaminant exposure for a vulnerable population of grizzly bears in the Canadian Rocky Mountains by determining if (1) dandelions (Taraxacum officinale) growing adjacent to a railway and grain spilled from hopper cars contain heavy metals, polycyclic aromatic hydrocarbons (PAHs), and mycotoxins and (2) metal concentrations from hair samples of individual bears correlates with use of the railway or other anthropogenic features. We used principle components analysis to represent 10 heavy metals and 16 PAHs and then compared their concentrations in railway-associated sources of grain and dandelions to reference samples that we purchased (grain) or sampled from nearby sites (dandelions). We also measured metal concentrations in the hair of bears that were captured and fitted with GPS collars. We found significantly higher concentrations in railway-associated samples of dandelion and grain for both metals (particularly lead, iron, and chromium), and the sum of 16 PAHs. Several metals and PAHs in railway-associated samples exceeded regulatory standards for soil or animal feed. Mycotoxins were detectable in grain samples, but occurred well below permissible standards. Metal concentrations in bear hair were not predicted by railway use, but higher metal concentrations occurred in male bears and two individuals that used ski hills during fall. As mitigation to reduce wildlife exposure to contaminants, particularly in protected areas, we encourage removal of railway grain deposits, regular maintenance of railway infrastructure, such as lubricating stations, and investigation of contaminants associated with other human infrastructures, such as ski hills.BACKGROUND Second-generation cryoballoon ablation is safe and effective in patients with persistent atrial fibrillation (AF). The aim of this study is to report the real long-term AF burden and freedom from AF post-cryoablation using continuous monitoring, and to assess whether intraoperative confirmation of pulmonary vein isolation using electrical mapping is necessary. METHODS A total of 33 patients (mean age 75.7 ± 5.6&nbsp;years, 16 men) with persistent AF who underwent second-generation cryoablation without electrical mapping were reviewed. All patients had a cardiac implantable device and were followed up for a mean of 755 ± 170&nbsp;days. RESULTS AF burden significantly decreased from 67.51% ± 34.90% to 18.28% ± 26.65% at 1-year follow-up, and this reduction was maintained at final follow-up (18.26% ± 23.70%, p  less then  0.001). Continuous monitoring revealed a freedom from AF rate of 33% and 24% at 1-year and full follow-up, respectively. Patients who remained in persistent AF at final follow-up had a trend towards higher pre-ablation AF burden (81.6% ± 29.7% vs 57.3% ± 36.4%, p = 0.08). CONCLUSION Second-generation cryoablation without confirming pulmonary vein isolation using electrical mapping is effective leading to significant reductions in AF burden based on continuous beat-to-beat monitoring at 1-year and long-term follow-up.Natural killer (NK) cells are cytotoxic lymphocytes of our immune system with the ability to identify and kill certain virally infected and tumor-transformed cells. During the past 15&nbsp;years, it has become increasingly clear that NK cells are involved in tumor immune surveillance and that they can be utilized to treat cancer patients. However, their ability to induce durable responses in settings of adoptive cell therapy needs to be further improved. One possible approach is to genetically engineer NK cells to augment their cytotoxicity per se, but also their ability to persist in vivo and home to the tumor-bearing tissue. In recent years, investigators have explored the potential of viral transduction and mRNA electroporation to modify NK cells. link2 Although these methods have generated promising data, they are associated with certain limitations. With the increasing advances in the CRISPR/Cas9 technology, investigators have now turned their attention toward using this technology with NK cells as an alternative method. In this book chapter, we introduce NK cells and provide an historical overview of techniques to genetically engineer lymphocytes. Further, we elucidate protocols for inducing double-strand breaks in NK cells via CRISPR/Cas9 together with readouts to address its efficacy and functional outcome. We also discuss the pros and cons of the described readouts. The overall aim of this book chapter is to help introduce the CRISPR/Cas9 technology to the broader audience of NK cell researchers.Innate lymphoid cells (ILCs) are emerging as important effectors of innate immunity and play a critical role in maintaining intestinal immune homeostasis. They are tissue-residing immune cells that can be subdivided based on master transcription factor and cytokine expression, bearing striking resemblance to their CD4+ T helper (Th) cell counterparts. ILCs are increasingly recognized as potential mediators of inflammatory bowel disease (IBD) providing a need to explore their functional and phenotypic differences in health vs. disease. In this chapter we outline protocols for the characterization of human ILCs and intracellular cytokine expression using flow cytometry. We include protocols for isolating human peripheral blood and colonic lamina propria mononuclear cells essential for evaluating human IBD specimens.Self-organizing mini-intestines cultured ex vivo from intestinal biopsy/resected samples, termed intestinal organoids or enteroids, present a unique opportunity for mechanistic investigation of health and disease of the intestinal epithelium. These patient-derived epithelial cultures are nontransformed, retain the genetic background of the patient, maintain regional specificity, differentiate into all major cell types of the intestinal epithelium, and are physiologically active. The biological relevance of human intestinal enteroids also circumvents the need for animal models for studies on the human gastrointestinal epithelium. Coculture with human endogenous microbes allows for exciting new studies on microbial-host interactions.While the popularity of organoids/enteroids for human research has risen drastically over the past decade, existing work and published methods are primarily limited to adult tissue. Here, we describe a concise and effective method for the establishment neonatal enteroids (including preterm and term) from surgically resected tissue or biopsy material. While the protocol works on adult tissue/biopsies, it has been specifically adopted and optimised for neonatal tissue. We detail the procedure at each stage ranging from human tissue collection and extraction of stem cells from the tissue, to passaging and general maintenance of organoid/enteroid lines, and how to freeze and revive lines as needed.The highly parallel nature of sequencing by synthesis (SBS) allows millions of amplicons to be sequenced simultaneously, which has led to enormous interest in the investigation of bacterial communities (often referred to as the microbiota). In this protocol, we describe a method for the 'universal' amplification of the v4 region of the bacterial 16S rRNA gene from genomic DNA and prepare these amplicons so that they can be sequenced using the MiSeq system (Illumina). The protocol provides instruction on sequencing of 188 genomic DNA samples plus PCR positive and negative controls, which can be applied to any sample type where bacterial DNA may be of interest.Innate lymphoid cells (ILCs) are important for both tissue immunity and tissue homeostasis. They are classified into three groups Group 1 ILCs include NK cells, which are important in eliciting immunity against intracellular pathogens; group 2 ILCs protect against parasitic helminths; and group 3 ILCs protect against extracellular pathogens. The role of ILCs in cancer immunity remains unclear. In this chapter, we discuss methods for isolating and characterizing tumor-infiltrating ILC subsets within the tumor microenvironment in an experimental murine model of B16 melanoma. link3 The chapter also highlights the expression of PD-1 on the various ILC subsets within the tumor microenvironment.