The outcome and cost-effectiveness of nurse-led care in people with rheumatoid arthritis: a multicentre randomised controlled trial.

Objective: To determine the clinical effectiveness and cost-effectiveness of nurse-led care (NLC) for people with rheumatoid arthritis (RA).

Methods: In a multicentre pragmatic randomised controlled trial, the assessment of clinical effects followed a non-inferiority design, while patient satisfaction and cost assessments followed a superiority design. Participants were 181 adults with RA randomly assigned to either NLC or rheumatologist-led care (RLC), both arms carrying out their normal practice.

Genome and transcriptome adaptation accompanying emergence of the definitive type 2 host-restricted Salmonella enterica serovar Typhimurium pathovar.

Salmonella enterica serovar Typhimurium definitive type 2 (DT2) is host restricted to Columba livia (rock or feral pigeon) but is also closely related to S. Typhimurium isolates that circulate in livestock and cause a zoonosis characterized by gastroenteritis in humans. DT2 isolates formed a distinct phylogenetic cluster within S.

Urethral adenocarcinoma associated with intestinal-type metaplasia, case report and literature review.

The presence of glandular epithelium in urinary tract biopsies poses a diagnostic challenge. Intestinal metaplasia of the urethra may be seen in many congenital, iatrogenic, and reactive conditions, as well as in association with malignant conditions such as urethral adenocarcinoma. We present a case of a 61 year-old woman presenting with microscopic hematuria.

Total synthesis and structural revision of viridicatumtoxin B.

Unlabelled:

Will The Real Viridicatumtoxin B Please Stand Up: Total synthesis of viridicatumtoxin B resulted in its structural revision and opens the way for analogue construction and biological evaluation of this complex tetracycline antibiotic. The highly convergent strategy employed allows for swift construction of the entire carbocyclic framework of the molecule.

Preferences for resuscitation and intubation among patients with do-not-resuscitate/do-not-intubate orders.

Objective: To determine the accuracy of do-not-resuscitate/do-not-intubate (DNR/DNI) orders in representing patient preferences regarding cardiopulmonary resuscitation (CPR) and intubation.

Patients And Methods: We conducted a prospective survey study of patients with documented DNR/DNI code status at an urban academic tertiary care center that serves approximately 250,000 patients per year. From October 1, 2010, to October 1, 2011, research staff enrolled a convenience sample of patients from the inpatient medical service, providing them with a series of emergency scenarios for which they related their treatment preference.

Polymerase IV occupancy at RNA-directed DNA methylation sites requires SHH1.

DNA methylation is an epigenetic modification that has critical roles in gene silencing, development and genome integrity. In Arabidopsis, DNA methylation is established by DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2) and targeted by 24-nucleotide small interfering RNAs (siRNAs) through a pathway termed RNA-directed DNA methylation (RdDM). This pathway requires two plant-specific RNA polymerases: Pol-IV, which functions to initiate siRNA biogenesis, and Pol-V, which functions to generate scaffold transcripts that recruit downstream RdDM factors.

Mitotic rate in melanoma: prognostic value of immunostaining and computer-assisted image analysis.

The prognostic value of mitotic rate in melanoma is increasingly recognized, particularly in thin melanoma in which the presence or absence of a single mitosis/mm can change staging from T1a to T1b. Still, accurate mitotic rate calculation (mitoses/mm) on hematoxylin and eosin (H&E)-stained sections can be challenging. Antimonoclonal mitotic protein-2 (MPM-2) and antiphosphohistone-H3 (PHH3) are 2 antibodies reported to be more mitosis-specific than other markers of proliferation such as Ki-67.

An uncommon Salter-Harris I fracture of the distal femoral physis with marked epiphyseal dislocation.

This is a report of an uncommon Salter-Harris I fracture of the distal femoral physis with complete dislocation of the distal epiphysis. These fractures are most frequently sustained during sports injuries, with motor vehicle accidents as another leading cause. They are at high risk of nonanatomic healing with subsequent varus or valgus deformity or premature growth arrest of the physis with subsequent leg length difference.

A genomewide mutagenesis screen identifies multiple genes contributing to Vi capsular expression in Salmonella enterica serovar Typhi.

A transposon-based, genomewide mutagenesis screen exploiting the killing activity of a lytic ViII bacteriophage was used to identify Salmonella enterica serovar Typhi genes that contribute to Vi polysaccharide capsule expression. Genes enriched in the screen included those within the viaB locus (tviABCDE and vexABCDE) as well as oxyR, barA/sirA, and yrfF, which have not previously been associated with Vi expression. The role of these genes in Vi expression was confirmed by constructing defined null mutant derivatives of S.

Interaction of Salmonella typhimurium with dendritic cells derived from pluripotent embryonic stem cells.

Using an in vitro differentiation protocol we isolated cells with the properties of dendritic cells (DCs) from immunologically refractive pluripotent murine embryonic stem cells (ESCs). These ES-derived dendritic cells (ESDCs) expressed cytokines and were able to present antigen to a T cell line. Infection of ESDCs with Salmonella Typhimurium stimulated the expression of immune cell markers and thousands of murine genes, many associated with the immune response.

Enhanced susceptibility to Citrobacter rodentium infection in microRNA-155-deficient mice.

MicroRNAs (miRNAs) are small noncoding molecules that control gene expression posttranscriptionally, with microRNA-155 (miR-155) one of the first to be implicated in immune regulation. Here, we show that miR-155-deficient mice are less able to eradicate a mucosal Citrobacter rodentium infection than wild-type C57BL/6 mice. miR-155-deficient mice exhibited prolonged colonization associated with a higher C.

The effect of long-term use of U-500 insulin via continuous subcutaneous infusion on durability of glycemic control and weight in obese, insulin-resistant patients with type 2 diabetes.

Objective: To evaluate the long-term efficacy and safety of U-500 insulin administered via continuous subcutaneous insulin infusion (CSII) in patients with insulin-resistant type 2 diabetes and high insulin requirements.

Methods: We retrospectively reviewed the effects of U-500 insulin administered via CSII on durability of glycemic control (HbA1c), body weight, total daily insulin dose, and incidence of hypoglycemia in 59 patients with insulin-resistant type 2 diabetes (duration of treatment 1 to 9.5 years; mean treatment duration 49 months).

Multilocus sequence typing of Histoplasma capsulatum in formalin-fixed paraffin-embedded tissues from cats living in non-endemic regions reveals a new phylogenetic clade.

Infections caused by Histoplasma capsulatum are found most often in endemic regions of North, Central, and South America. H. capsulatum has been divided into eight geographic clades by multi-locus sequence typing (MLST).

Teaching quality essentials: the effectiveness of a team-based quality improvement curriculum in a tertiary health care institution.

A unique quality improvement (QI) curriculum was implemented within the Division of General Internal Medicine to improve QI knowledge through multidisciplinary, team-based education, which also met the QI requirement for the American Board of Internal Medicine (ABIM) Maintenance of Certification (MOC) and the Mayo Quality Fellows program. Participants completed up to 4 QI learning modules, including pretest and posttest assessments. A participant who successfully completed all 4 modules received certification as a Silver Quality Fellow and credit toward the quality requirement for ABIM MOC.

DDR complex facilitates global association of RNA polymerase V to promoters and evolutionarily young transposons.

The plant-specific DNA-dependent RNA polymerase V (Pol V) evolved from Pol II to function in an RNA-directed DNA methylation pathway. Here, we have identified targets of Pol V in Arabidopsis thaliana on a genome-wide scale using ChIP-seq of NRPE1, the largest catalytic subunit of Pol V. We found that Pol V is enriched at promoters and evolutionarily recent transposons.

Tai Chi exercise and auricular acupressure for people with rheumatoid arthritis: an evaluation study.

Aims And Objectives: (i) To assess the effectiveness of Tai Chi exercise in people with rheumatoid arthritis (RA). (ii) To ascertain if Tai Chi and auricular acupressure have a potentiation effect in controlling pain. (iii) To evaluate the acceptability and enjoyment of the classes.

FGF21 promotes metabolic homeostasis via white adipose and leptin in mice.

Fibroblast growth factor 21 (FGF21) is a potent metabolic regulator, and pharmacological administration elicits glucose and lipid lowering responses in mammals. To delineate if adipose tissue is the predominant organ responsible for anti-diabetic effects of FGF21, we treated mice with reduced body fat (lipodystrophy mice with adipose specific expression of active sterol regulatory element binding protein 1c; Tg) with recombinant murine FGF21 (rmuFGF21). Unlike wildtype (WT) mice, Tg mice were refractory to the beneficial effects of rmuFGF21 on body weight, adipose mass, plasma insulin and glucose tolerance.

DNA methyltransferases are required to induce heterochromatic re-replication in Arabidopsis.

The relationship between epigenetic marks on chromatin and the regulation of DNA replication is poorly understood. Mutations of the H3K27 methyltransferase genes, Arabidopsis trithorax-related protein5 (ATXR5) and ATXR6, result in re-replication (repeated origin firing within the same cell cycle). Here we show that mutations that reduce DNA methylation act to suppress the re-replication phenotype of atxr5 atxr6 mutants.

The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration.

Cells often migrate in vivo in an extracellular matrix that is intrinsically three-dimensional (3D) and the role of actin filament architecture in 3D cell migration is less well understood. Here we show that, while recently identified linkers of nucleoskeleton to cytoskeleton (LINC) complexes play a minimal role in conventional 2D migration, they play a critical role in regulating the organization of a subset of actin filament bundles - the perinuclear actin cap - connected to the nucleus through Nesprin2giant and Nesprin3 in cells in 3D collagen I matrix. Actin cap fibers prolong the nucleus and mediate the formation of pseudopodial protrusions, which drive matrix traction and 3D cell migration.

Absorption, Metabolism, and Excretion of [(14) C]-Tivozanib, a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Healthy Male Participants: A Phase I, Open-Label, Mass-Balance Study.

Objective: To evaluate the absorption, metabolism, and excretion of tivozanib, a new investigational drug for renal cell carcinoma and solid malignancies.

Methods: Eight healthy male participants received a single 1.5-mg (˜160 μCi) dose of oral [(14) C]-tivozanib.

Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance.

The advent of organic synthesis and the understanding of the molecule as they occurred in the nineteenth century and were refined in the twentieth century constitute two of the most profound scientific developments of all time. These discoveries set in motion a revolution that shaped the landscape of the molecular sciences and changed the world. Organic synthesis played a major role in this revolution through its ability to construct the molecules of the living world and others like them whose primary element is carbon.

A total synthesis trilogy: calicheamicin γ1(I), Taxol®, and brevetoxin A.

Detailed behind-the-scenes accounts of the total syntheses of calicheamicin γ(1)(I), Taxol(®), and brevetoxin A are discussed with particular emphasis placed on strategies and tactics employed in these campaigns.

The role of sphingosine-1-phosphate transporter Spns2 in immune system function.

Sphingosine-1-phosphate (S1P) is lipid messenger involved in the regulation of embryonic development, immune system functions, and many other physiological processes. However, the mechanisms of S1P transport across cellular membranes remain poorly understood, with several ATP-binding cassette family members and the spinster 2 (Spns2) member of the major facilitator superfamily known to mediate S1P transport in cell culture. Spns2 was also shown to control S1P activities in zebrafish in vivo and to play a critical role in zebrafish cardiovascular development.

INVOLVED IN DE NOVO 2-containing complex involved in RNA-directed DNA methylation in Arabidopsis.

At least three pathways control maintenance of DNA cytosine methylation in Arabidopsis thaliana. However, the RNA-directed DNA methylation (RdDM) pathway is solely responsible for establishment of this silencing mark. We previously described INVOLVED IN DE NOVO 2 (IDN2) as being an RNA-binding RdDM component that is required for DNA methylation establishment.