Quantification of Macrophage-Driven Inflammation During Myocardial Infarction with F-LW223, a Novel TSPO Radiotracer with Binding Independent of the rs6971 Human Polymorphism.

Myocardial infarction (MI) is one of the leading causes of death worldwide, and inflammation is central to tissue response and patient outcomes. The 18-kDa translocator protein (TSPO) has been used in PET as an inflammatory biomarker. The aims of this study were to screen novel, fluorinated, TSPO radiotracers for susceptibility to the rs6971 genetic polymorphism using in vitro competition binding assays in human brain and heart; assess whether the in vivo characteristics of our lead radiotracer, F-LW223, are suitable for clinical translation; and validate whether F-LW223 can detect macrophage-driven inflammation in a rat MI model.

Adiposity, Physical Function, and Their Associations With Insulin Resistance, Inflammation, and Adipokines in CKD.

Rationale & Objectives: Adiposity and physical fitness levels are major drivers of cardiometabolic risk, but these relationships have not been well-characterized in chronic kidney disease (CKD). We examined the associations of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intrahepatic fat, and physical function with inflammation, insulin resistance, and adipokine levels in patients with CKD.

Study Design: Prospective cohort study.

Genetic interaction between central pair apparatus genes CFAP221, CFAP54, and SPEF2 in mouse models of primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous syndrome that results from defects in motile cilia. The ciliary axoneme has a 9 + 2 microtubule structure consisting of nine peripheral doublets surrounding a central pair apparatus (CPA), which plays a critical role in regulating proper ciliary function. We have previously shown that mouse models with mutations in CPA genes CFAP221, CFAP54, and SPEF2 have a PCD phenotype with defects in ciliary motility.

The impact of a quality management program for patients undergoing head and neck resection with free-flap reconstruction: longitudinal study examining sustainability.

Background: Care pathways (CPs) are helpful in reducing unwanted variation in clinical care. Most studies of CPs show they improve clinical outcomes but there is little known about the long-term impact of CPs as part of a sustained quality management program. Head and neck (HN) surgery with free flap reconstruction is complex, time-consuming and expensive.

Designing and integrating a quality management program for patients undergoing head and neck resection with free-flap reconstruction.

Background: Care pathways (CPs) offer a proven method of systematically improving patient care. CPs are particularly helpful in complex clinical conditions where variation in care is a problem such as patients undergoing major head and neck resection with free flap reconstruction. Although CPs have been used to manage this patient group, most CPs are implemented as part of relatively short-term quality improvement projects.

Parenteral thiamine for prevention and treatment of delirium in critically ill adults: a systematic review protocol.

Background: Delirium is an acute confusional state, common in critical illness and associated with cognitive decline. There is no effective pharmacotherapy to prevent or treat delirium, although it is scientifically plausible that thiamine could be effective. Thiamine studies in dementia patients are inconclusive.

Through-Space Polar-π Interactions in 2,6-Diarylthiophenols.

The front cover artwork is provided by Marijn Maas from the group of Prof. Jasmin Mecinović (University of Southern Denmark). The image shows the stabilization of thiols by aromatic rings, as a result of energetically favorable SH-π interactions in a designed small molecule and in proteins.

Adipose tissue-liver crosstalk during pathologic changes caused by vinyl chloride metabolites in mice.

Volatile organic compounds (VOCs), such as vinyl chloride (VC), can be directly toxic at high concentrations. However, we have shown that 'nontoxic' exposures to VC and its metabolite chloroethanol (CE) enhances experimental non-alcoholic fatty liver disease (NAFLD), suggesting an unpredicted interaction. Importantly, VOC exposure has been identified as a potential risk factor for the development of obesity and its sequelae in humans.

Morphology of the Amazonian Teleost Genus Using Advanced 3D Imaging.

The arapaima is the largest of the extant air-breathing freshwater fishes. Their respiratory gas bladder is arguably the most striking of all the adaptations to living in the hypoxic waters of the Amazon basin, in which dissolved oxygen can reach 0 ppm (0 mg/l) at night. As obligatory air-breathers, arapaima have undergone extensive anatomical and physiological adaptations in almost every organ system.

The novel E. coli cell division protein, YtfB, plays a role in eukaryotic cell adhesion.

Characterisation of protein function based solely on homology searches may overlook functions under specific environmental conditions, or the possibility of a protein having multiple roles. In this study we investigated the role of YtfB, a protein originally identified in a genome-wide screen to cause inhibition of cell division, and has demonstrated to localise to the Escherichia coli division site with some degree of glycan specificity. Interestingly, YtfB also shows homology to the virulence factor OapA from Haemophilus influenzae, which is important for adherence to epithelial cells, indicating the potential of additional function(s) for YtfB.

Metal-Organic Frameworks with Hexakis(4-carboxyphenyl)benzene: Extensions to Reticular Chemistry and Introducing Foldable Nets.

Nine metal-organic frameworks have been prepared with the hexagon-shaped linker 1,2,3,4,5,6-hexakis(4-carboxyphenyl)benzene (Hcpb) by solvothermal reactions in dimethylformamide (dmf) or dimethylacetamide (dmac) with acetic acid or formic acid as modulators: [Bi(cpb)(acetato)(dmf)]·2dmf forms a -net; 2(HNMe)[Cu(cpb)] forms a -net; [Fe(cpb)(acetato)(dmf)] and [Co(cpb)(acetato)(dmf)] are isostructural and form -nets; 2(HNEt)[Fe(cpb)] and the two polymorphs of 2(HNMe)[Zn(cpb)]·1.5dmac, and , show -nets; [Cu(cpb)(acetato)(dmf)]·2dmf, , forms a mixed coordination and hydrogen-bonded -net; and 2(HNMe)[Zn(cpb)] , a similarly mixed -net. Surface area values (Brunauer-Emmett-Teller, BET) range from 34 m g for to 303 m g for for samples activated at 120 °C in dynamic vacuum.

Through-Space Polar-π Interactions in 2,6-Diarylthiophenols.

Molecular recognition between polar groups and aromatic molecules is fundamentally important to rational drug design. Although it has been well established that many polar functionalities interact with electron-rich aromatic residues through energetically favorable polar-π interactions, there is a limited understanding of the association between thiols and aromatic systems. Herein we report physical-organic chemistry studies on 2,6-diarylthiophenols that possess the central thiophenol ring and two flanking aromatic rings with tunable electronic properties caused by substituents at distant para position.

Activation of μ-opioid receptors by MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) and its fluorinated derivatives.

Background And Purpose: A fluorinated derivative (2F-MT-45) of the synthetic μ-opioid receptor agonist MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) was recently identified in a seized illicit tablet. While MT-45 is a Class A drug, banned in a number of countries, nothing is known about the pharmacology of 2F-MT-45. This study compares the pharmacology of MT-45, its fluorinated derivatives and two of its metabolites.

Cell-to-cell spread of vaccinia virus is promoted by TGF-β-independent Smad4 signalling.

The induction of Smad signalling by the extracellular ligand TGF-β promotes tissue plasticity and cell migration in developmental and pathological contexts. Here, we show that vaccinia virus (VACV) stimulates the activity of Smad transcription factors and expression of TGF-β/Smad-responsive genes at the transcript and protein levels. Accordingly, infected cells share characteristics to those undergoing TGF-β/Smad-mediated epithelial-to-mesenchymal transition (EMT).

Correction: Fungal Alkaloid Occurrence in Endophyte-Infected Perennial Ryegrass during Seedling Establishment.

The original version of this article unfortunately contained a mistake. There is a mistake in the affiliation section and Figure 6. The correct affiliation and Figure 6 are shown here.

Enzyme replacement in advanced pancreatic cancer: patient perceptions.

Purpose: Advanced pancreatic cancer has a universally poor survival rate. Patients frequently develop malabsorption that requires pancreatic enzyme replacement therapy (PERT). This study explores the experience of patient engagement with PERT and how the medication is taken and tolerated.

Evaluation of prophylactic antibiotics in penetrating brain injuries at an academic level 1 trauma center.

Objective: Infections from penetrating brain injuries (PBI) lead to higher morbidity and mortality rates. The results of this research will be evaluated to develop institutional guideline for antibiotic prophylaxis in this patient population. The objective was to characterize the prophylactic antibiotic usage for patients presenting with PBI.

Association of Adverse Childhood Experiences With Childhood Atopic Dermatitis in the United States.

Traumatic and stressful events of childhood, known as adverse childhood experiences (ACEs), have been associated with numerous health outcomes. However, little is known about ACEs in atopic dermatitis (AD) patients. We sought to determine the relationship between ACEs and childhood AD.

Structure-Activity Relationship Studies of Tetrahydroquinolone Free Fatty Acid Receptor 3 Modulators.

Free fatty acid receptor 3 (FFA3, previously GPR41) is activated by short-chain fatty acids, mediates health effects of the gut microbiota, and is a therapeutic target for metabolic and inflammatory diseases. The shortage of well-characterized tool compounds has however impeded progress. Herein, we report structure-activity relationship of an allosteric modulator series and characterization of physicochemical and pharmacokinetic properties of selected compounds, including previous and new tools.

Fungal Alkaloid Occurrence in Endophyte-Infected Perennial Ryegrass during Seedling Establishment.

The symbiotic Epichloë festucae var. lolii endophyte produces alkaloids which can provide its host grass, perennial ryegrass (Lolium perenne L), with a selective advantage in both natural and agricultural managed ecosystems. This study focuses on understanding the alkaloid concentrations that occur in endophyte-infected perennial ryegrass during the early establishment phase.

A field-based investigation of behavioural interactions between invasive green crab (), rock crab (), and American lobster () in southern Newfoundland.

Marine species invasions pose a global threat to native biodiversity and commercial fisheries. The European green crab () is one of the most successful marine invaders worldwide and has, in the last decade, invaded the southern and western coastal waters of the island of Newfoundland, Newfoundland and Labrador (NL), Canada. Impacts of green crab on the American lobster (), which are native to Newfoundland, are not well understood, particularly for interactions around deployed fishing gear.