Interleukin-4 downregulates transcription factor BCL6 to promote memory B cell selection in germinal centers.

Germinal center (GC)-derived memory B cells (MBCs) are critical for humoral immunity as they differentiate into protective antibody-secreting cells during re-infection. GC formation and cellular interactions within the GC have been studied in detail, yet the exact signals that allow for the selection and exit of MBCs are not understood. Here, we showed that IL-4 cytokine signaling in GC B cells directly downregulated the transcription factor BCL6 via negative autoregulation to release cells from the GC program and to promote MBC formation.

Transition-Metal-Free Continuous-Flow Synthesis of 2,5-Diaryl Furans: Access to Medicinal Building Blocks and Optoelectronic Materials.

The direct transformation of 1,3-dienes into valuable 2,5-diarylfurans using transition-metal-free conditions is presented. By employing a simple oxidation─dehydration sequence on readily accessible 1,3-dienes, important 2,5-diarylfuran building blocks frequently used in medicinal and material chemistry are prepared. The oxidation step is realized using singlet oxygen, and the intermediate endoperoxide is dehydrated under metal-free conditions and at ambient temperature using the Appel reagent.

Early T-bet promotes LFA1 upregulation required for CD8+ effector and memory T cell development.

The T-box transcription factor T-bet is regarded as a "master regulator" of CD4+ Th1 differentiation and IFN-γ production. However, in multiple models of infection, T-bet appears less critical for CD8+ T cell expansion and effector function. Here, we show that following vaccination with a replication-deficient strain of Toxoplasma gondii, CD8+ T cell expression of T-bet is required for optimal expansion of parasite-specific effector CD8+ T cells.

The experiences and perceptions of wellbeing provision among English ambulance services staff: a multi-method qualitative study.

Background: NHS ambulance service staff are at risk of poor physical and mental wellbeing because of the likelihood of encountering stressful and traumatic incidents. While reducing sickness absence and improving wellbeing support to ambulance staff is a key NHS priority, few studies have empirically documented a national picture to inform policy and service re-design. The study aimed to understand how ambulance service trusts in England deal with staff health and wellbeing, as well as how the staff perceive and use wellbeing services.

cDC1 coordinate innate and adaptive responses in the omentum required for T cell priming and memory.

In the peritoneal cavity, the omentum contains fat-associated lymphoid clusters (FALCs) whose role in response to infection is poorly understood. After intraperitoneal immunization with , conventional type 1 dendritic cells (cDC1s) were critical to induce innate sources of IFN-γ and cellular changes in the FALCs. Unexpectedly, infected peritoneal macrophages that migrated into the FALCs primed CD8 T cells.

Nicotine replacement therapy 'gift cards' for hospital inpatients who smoke: a prospective before-and-after controlled pilot evaluation.

Introduction: A common barrier identified by individuals trying to quit smoking is the cost of cessation pharmacotherapies. The purpose of this evaluation was to: (1) Assess the feasibility of offering nicotine replacement therapy (NRT) 'gift cards' to hospitalised smokers for use posthospitalisation; and, (2) Estimate the effect of providing NRT gift cards on 6-month smoking abstinence.

Methods: A prospective, quasi-experimental, before-and-after controlled cohort design with random sampling was used to compare patients who had received the Ottawa Model for Smoking Cessation (OMSC) intervention ('control') with patients who received the OMSC plus a $C300 Quit Card ('QCI'), which they could use to purchase any brand or form of NRT from any Canadian pharmacy.

Strategies to improve smoking cessation rates in primary care.

Background: Primary care is an important setting in which to treat tobacco addiction. However, the rates at which providers address smoking cessation and the success of that support vary. Strategies can be implemented to improve and increase the delivery of smoking cessation support (e.

Indium-Mediated 2-Oxonia Cope Rearrangement of 1,4-Dienols to 1,3-Dienols.

An indium-mediated isomerization of 1,4-dienols to 1,3-dienols is described. This procedure consists of the addition of pentadienylindium, in a protic solvent, to aldehydes giving the kinetic γ-allylation product in high yields. The subsequent conversion of this γ-allylation product to its thermodynamic 1,3-dienol α-isomer can be achieved by its exposure to indium triflate in the presence of a substoichiometric amount of aldehyde at room temperature.

Total Synthesis of the Tetrasubstituted Furan Fatty Acid Metabolite CeDFP via Au-Catalyzed Intermolecular Alkyne Hydroarylation.

The first total synthesis of the tetrasubstituted furan fatty acid (FFA) metabolite 5-[(1 E)-2-carboxyethenyl]-3,4-dimethyl-2-furanpentanoic acid (CeDFP) is reported. CeDFP is a FFA metabolite isolated from shark livers and is related to the known FFA metabolites CMPF and CMPentylF. Key elements of the synthetic route to CeDFP include an iodine-promoted 5- endo- dig cyclization of a 1,2-alkyne diol, a methyllithium-mediated insertion of the C-methyl group, and a Au(I)-catalyzed intermolecular hydroarylation to introduce the unsaturated ester.

Frailty in the Cardiac Surgical Patient: Comparison of Frailty Tools and Associated Outcomes.

Background: Frailty measurement in cardiac surgery is poorly studied. The study purposes were to identify a simple but accurate frailty tool by comparing the simplified frailty index, Study of Osteoporotic Fractures (SOF), to a more complex frailty index, the Cardiovascular Health Study (CHS), and outcomes of frail patients to nonfrail patients.

Methods: Patients aged 65 years or older admitted for elective coronary artery bypass grafting (CABG), valvular surgery (valve), or a combination of CABG/valve were recruited and administered the SOF and CHS indexes.

The evolving role of T-bet in resistance to infection.

The identification of T-bet as a key transcription factor associated with the development of IFNγ-producing CD4 T cells predicted a crucial role for T-bet in cell-mediated immunity and in resistance to many intracellular infections. This idea was reinforced by initial reports showing that T-bet-deficient mice were more susceptible to pathogens that survived within the lysosomal system of macrophages. However, subsequent studies revealed IFNγ-dependent, T-bet-independent pathways of resistance to diverse classes of microorganisms that occupy other intracellular niches.

Extended Treatment with Glial Cell Line-Derived Neurotrophic Factor in Parkinson's Disease.

Background: Intraputamenal glial cell line-derived neurotrophic factor (GDNF), administered every 4 weeks to patients with moderately advanced Parkinson's disease, did not show significant clinical improvements against placebo at 40 weeks, although it significantly increased [18F]DOPA uptake throughout the entire putamen.

Objective: This open-label extension study explored the effects of continued (prior GDNF patients) or new (prior placebo patients) exposure to GDNF for another 40 weeks.

Methods: Using the infusion protocol of the parent study, all patients received GDNF without disclosing prior treatment allocations (GDNF or placebo).

Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson's disease.

We investigated the effects of glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease, using intermittent intraputamenal convection-enhanced delivery via a skull-mounted transcutaneous port as a novel administration paradigm to potentially afford putamen-wide therapeutic delivery. This was a single-centre, randomized, double-blind, placebo-controlled trial. Patients were 35-75 years old, had motor symptoms for 5 or more years, and presented with moderate disease severity in the OFF state [Hoehn and Yahr stage 2-3 and Unified Parkinson's Disease Rating Scale motor score (part III) (UPDRS-III) between 25 and 45] and motor fluctuations.

Confirmatory factor analysis of the Minnesota living with heart failure questionnaire among patients following open heart surgery for valve dysfunction.

Introduction: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) was designed to assess the impact of the adverse effects of heart failure (HF). Numerous reports suggest an additional third factor with the proposed third factor representing a social dimension. The purpose of this study was to use confirmatory factor analysis (CFA) to validate the factor structure of the MLWHFQ, and examine a proposed third factor structure.

Resolvin E1 (R E ) attenuates LPS induced inflammation and subsequent atrophy in C2C12 myotubes.

Resolution of inflammation is now known to be an active process which in part is instigated and controlled by specialized pro-resolving lipid mediators (SPM's) derived from dietary omega-3 fatty acids. Resolvin E1 (R E ) is one of these SPM's derived from the omega-3 fatty acid eicosapentaenoic acid. Using both molecular and phenotypic functional measures we report that in a model of Lipopolysaccharide (LPS) induced inflammation, R E attenuated mRNA levels of both interlukin-6 and monocyte chemoattractant protein-1 whilst having no effect on tumor necrosis factor-α or interlukin-1β in C2C12 skeletal muscle myotubes.

Group 1 Innate Lymphoid Cell Lineage Identity Is Determined by a cis-Regulatory Element Marked by a Long Non-coding RNA.

Commitment to the innate lymphoid cell (ILC) lineage is determined by Id2, a transcriptional regulator that antagonizes T and B cell-specific gene expression programs. Yet how Id2 expression is regulated in each ILC subset remains poorly understood. We identified a cis-regulatory element demarcated by a long non-coding RNA (lncRNA) that controls the function and lineage identity of group 1 ILCs, while being dispensable for early ILC development and homeostasis of ILC2s and ILC3s.

A biosynthetically inspired route to substituted furans using the Appel reaction: total synthesis of the furan fatty acid F.

Appel reaction conditions have been harnessed to affect a mild biosynthetically inspired dehydration of endoperoxides to deliver multi-substituted electron rich furans. Unlike traditional dehydrative procedures, this method is metal and acid free, and can be achieved under redox neutral conditions. It is general for a range of aryl and alkyl substituted endoperoxides, and is functional group tolerant.

A single center's experience with pacemaker implantation after the Cox maze procedure for atrial fibrillation.

Objective: The Cox maze procedure (CM) is safe and effective for all atrial fibrillation (AF) types. A recent randomized trial found alarming rates of pacemaker implantation (PMI) during hospitalization after CM. The purpose of this study was to assess the rate of PMI and its impact on outcomes after CM.

The Effect of Initiation of a Transcatheter Aortic Valve Replacement Program in the Treatment of Severe Aortic Stenosis.

We assessed the effect of a transcatheter aortic valve replacement (TAVR) program and Heart Team concept on our approach to severe isolated symptomatic aortic stenosis (AS) with regard to surgical practice, patient selection, perioperative outcomes, 1-year survival, and AVR volume. TAVR program began in August 2011. Patients having isolated surgical AVR between January 2008 and August 2011, when the program began (n = 282, 42 months), were compared with those after the program began until February 2015 (n = 344, surgical AVR and n = 126, TAVR, 42 months).

Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system.

An important function of the blood-brain barrier is to exclude pathogens from the central nervous system, but some microorganisms benefit from the ability to enter this site. It has been proposed that Toxoplasma gondii can cross biological barriers as a motile extracellular form that uses transcellular or paracellular migration, or by infecting a host cell that then crosses the blood-brain barrier. Unexpectedly, analysis of acutely infected mice revealed significant numbers of free parasites in the blood and the presence of infected endothelial cells in the brain vasculature.

Health-Related Quality of Life After Minimally Invasive Cardiac Surgery.

Objective: Factors influencing health-related quality of life (HRQL) after minimally invasive cardiac surgery have not been well described. We examined the trajectory of HRQL after minimally invasive cardiac surgery and the role of perioperative factors and rhythm on HRQL changes.

Methods: Patients underwent minimally invasive surgical ablation for atrial fibrillation and/or valve surgery (n = 235).

Comparison of EuroSCORE II, Original EuroSCORE, and The Society of Thoracic Surgeons Risk Score in Cardiac Surgery Patients.

Background: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II was developed to reflect a more current dataset and evidence-based improvements in cardiac surgery. In the United States, The Society of Thoracic Surgeons (STS) risk score is more accepted owing to relatively high predictive value despite less user friendliness and inapplicability to some cardiac surgeries. We compared the precision of EuroSCORE II with EuroSCORE I and the STS risk score for operative mortality.