Safety and efficacy of the tumor-selective adenovirus enadenotucirev, in combination with nivolumab, in patients with advanced/metastatic epithelial cancer: a phase I clinical trial (SPICE).

Background: Novel combination therapies to overcome anti-PD-1 resistance are required. Enadenotucirev, a tumor-selective blood stable adenoviral vector, has demonstrated a manageable safety profile and ability to increase tumor immune-cell infiltration in phase I studies in solid tumors.

Methods: We conducted a phase I multicenter study of intravenous enadenotucirev plus nivolumab in patients with advanced/metastatic epithelial cancer not responding to standard therapy.

Target engagement and cellular fate of otelixizumab: a repeat dose escalation study of an anti-CD3ε mAb in new-onset type 1 diabetes mellitus patients.

Aims: This paper describes the pharmacological findings from a study where otelixizumab, an anti-CD3ɛ mAb, was dosed in new onset Type 1 diabetes mellitus (NOT1DM) patients. This is the first time that the full dose-response of an anti-CD3ɛ mAb has been investigated in the clinic. The data have been validated using a previously developed pharmacokinetic/pharmacodynamic (PK/PD) model of otelixizumab to simulate the interplay between drug administration, CD3ɛ target engagement and downmodulation.

Acetosyringone treatment duration affects large T-DNA molecule transfer to rice callus.

Background: Large T-DNA fragment transfer has long been a problem for Agrobacterium-mediated transformation. Although vector systems, such as the BIBAC series, were successfully developed for the purpose, low transformation efficiencies were consistently observed.

Results: To gain insights of this problem in monocot transformation, we investigated the T-strand accumulation of various size of T-DNA in two kinds of binary vectors (one copy vs.

Best practices in performing flow cytometry in a regulated environment: feedback from experience within the European Bioanalysis Forum.

Flow cytometry is a powerful tool that can be used for the support of (pre)clinical studies. Although various white papers are available that describe the set-up and validation of the instrumentation (the flow cytometer) and validation of flow cytometry methods, to date no guidelines exist that address the requirements for performing flow cytometry in a regulated environment. In this manuscript, the European Bioanalysis Forum presents additional practice guidance on the use of flow cytometry in the support of drug development programs and addresses areas that are not covered in the previous publications.

Association Between Midlife Cardiorespiratory Fitness and Risk of Stroke: The Cooper Center Longitudinal Study.

Background And Purpose: Low cardiorespiratory fitness (CRF) is associated with an increased risk of stroke. However, the extent to which this association is explained by the development of stroke risk factors such as diabetes mellitus, hypertension, and atrial fibrillation is unknown. We evaluated the relationship between midlife CRF and risk of stroke after the age of 65 years, independent of the antecedent risk factor burden.

Class II Resin Composites: Restorative Options.

Tooth-coloured, resin composite restorations are amongst the most frequently prescribed forms of dental restoration to manage defects in posterior teeth. The attainment of a desirable outcome when placing posterior resin composite restorations requires the clinician to have a good understanding of the benefits (as well as the limitations) posed by this material, together with a sound knowledge of placement technique. Numerous protocols and materials have evolved to assist the dental operator with this type of demanding posterior restoration.

Refractory Epistaxis due to Severe Factor V Deficiency with Inhibitor.

Factor V deficiency secondary to inhibitors is extremely rare and can be caused by a wide collection of exposures such as bovine thrombin and beta lactamase antibiotics. The management of factor V deficiency with inhibitor is a condition treated based on case reports due to the rarity of this condition. We describe a complicated case of an elderly patient with severe factor V deficiency with high inhibitor titer refractory to FEIBA (anti-inhibitor coagulation complex) treated with NovoSeven concurrently with cyclosporine immunosuppression and Rituxan.

Atrial fibrillation ablation and left appendage closure in heart failure patients.

Purpose Of Review: Patients with atrial fibrillation and heart failure experience an increased morbidity and mortality from the hemodynamic consequences of atrial fibrillation and an increased stroke risk. Consequently, there has been increased attention to procedural alternatives to pharmacologic rhythm control and anticoagulation for stroke prevention. This review aims to evaluate the evidence for atrial fibrillation ablation and left atrial appendage closure in heart failure patients.

Changes in mid-life fitness predicts heart failure risk at a later age independent of interval development of cardiac and noncardiac risk factors: the Cooper Center Longitudinal Study.

Aims: Low mid-life fitness is associated with higher risk for heart failure (HF). However, it is unclear to what extent this HF risk is modifiable and mediated by the burden of cardiac and noncardiac comorbidities. We studied the effect of cardiac and noncardiac comorbidities on the association of mid-life fitness and fitness change with HF risk.

Overexpression of ubiquitin-like LpHUB1 gene confers drought tolerance in perennial ryegrass.

HUB1, also known as Ubl5, is a member of the subfamily of ubiquitin-like post-translational modifiers. HUB1 exerts its role by conjugating with protein targets. The function of this protein has not been studied in plants.

Clinical intervention for quality improvement of gastric-emptying studies.

Unlabelled: Prompted by clinical concerns for false-negative tests, we implemented a clinical intervention consisting of a training session and an image-based verification procedure to document homogeneous radioactivity distribution in the radiolabeled meal (egg substitute per the guideline).

Methods: A technologist training session emphasized the importance of thorough mixing of (99m)Tc-sulfur colloid in the egg meal. For 6 mo after training, an image of the prepared mixed egg was acquired before patient ingestion.

A novel RNA binding protein affects rbcL gene expression and is specific to bundle sheath chloroplasts in C4 plants.

Background: Plants that utilize the highly efficient C4 pathway of photosynthesis typically possess kranz-type leaf anatomy that consists of two morphologically and functionally distinct photosynthetic cell types, the bundle sheath (BS) and mesophyll (M) cells. These two cell types differentially express many genes that are required for C4 capability and function. In mature C4 leaves, the plastidic rbcL gene, encoding the large subunit of the primary CO2 fixation enzyme Rubisco, is expressed specifically within BS cells.

Hypereosinophilic syndrome with cardiac involvement in a pregnant patient with multiple sclerosis.

In hypereosinophilic syndrome, the sustained overproduction of eosinophils leads to the dysfunction of one or more organs. Symptoms vary in accordance with which organ is affected. Cardiac involvement leads to substantial morbidity and to most of the deaths that are associated with hypereosinophilic syndrome.

Development of a rapid biolistic assay to determine changes in relative levels of intracellular calcium in leaves following tetracycline uptake by pinto bean plants.

Tetracycline antibiotics, such as chlortetracycline (CTC) and tetracycline (TC), are introduced into agricultural lands through the application of manure as fertilizer. These compounds are phytotoxic to certain crop plants, including pinto beans (Phaseolus vulgaris), the species used for this investigation. While the mechanism of this toxicity is not yet understood, CTC is known to be a calcium chelator.

Rubisco gene expression in C4 plants.

In leaves of most C(4) plants, ribulose 1,5 bisphosphate carboxylase (Rubisco) accumulates only in bundle sheath (bs) cells that surround the vascular centres, and not in mesophyll (mp) cells. It has been shown previously that in the C(4) dicots amaranth and Flaveria bidentis, post-transcriptional control of mRNA translation and stability mediate the C(4) expression patterns of genes encoding the large and small Rubisco subunits (chloroplast rbcL and nuclear RbcS, respectively). Translational control appears to regulate bs cell-specific Rubisco gene expression during early dicot leaf development, while control of mRNA stability appears to mediate bs-specific accumulation of RbcS and rbcL transcripts in mature leaves.

The Lem2 gene promoter of barley directs cell- and development-specific expression of gfp in transgenic plants.

Transgenic approaches to combating fungal pathogens, such as Fusarium graminearum, require the targeting of antifungal gene expression in tissues of developing seed spikes of cereal grains, especially lemmas and epicarps. The Lem2 gene of barley encodes a lectin-like protein that is strongly up-regulated by salicylic acid and is preferentially expressed in lemmas, paleas (lemma/palea) and coleoptiles. Transient expression studies have indicated that the proximal -75/+70 region (relative to the transcription start site) determines organ specificity.

Role of myosin regulatory light chain and Rac1 in the migration of polyamine-depleted intestinal epithelial cells.

We have previously shown that polyamine depletion decreased migration, Rac activation, and protein serine threonine phosphatase 2A activity. We have also shown that polyamine depletion increased cortical F-actin and decreased lamellipodia and stress fibers. In this study, we used staurosporine (STS), a potent, cell-permeable, and broad-spectrum serine/threonine kinase inhibitor, and studied migration.

Untranslated regions of FbRbcS1 mRNA mediate bundle sheath cell-specific gene expression in leaves of a C4 plant.

C4 photosynthesis typically requires two specialized leaf cell types, bundle sheath (bs) and mesophyll (mp), which provide the foundation for this highly efficient carbon assimilation pathway. In leaves of Flaveria bidentis, a dicotyledonous C4 plant, ribulose 1,5-bisphosphate carboxylase (rubisco) accumulates only in bs cells surrounding the vascular centers and not in mp cells. This is in contrast to the more common C3 plants, which accumulate rubisco in all photosynthetic cells.

Palliation of patients with malignant gastroduodenal obstruction with self-expanding metallic stents: the treatment of choice?

Background: Gastroduodenal obstruction is a common preterminal event for patients with gastric and pancreatic cancer who often undergo palliative surgical bypass. Endoscopic palliation with self-expanding metallic stents has emerged as a safe and an effective alternative to surgery, but experience with the technique remains limited.

Methods: Twenty-eight patients hospitalized with GI obstruction because of incurable gastric or pancreatic cancer were recruited for a prospective study of palliation with self-expanding metallic stents.

Untranslated regions from C4 amaranth AhRbcS1 mRNAs confer translational enhancement and preferential bundle sheath cell expression in transgenic C4 Flaveria bidentis.

Many aspects of photosynthetic gene expression are posttranscriptionally regulated in C4 plants. To determine if RbcS mRNA untranslated regions (UTRs) in themselves could confer any characteristic C4 expression patterns, 5'- and 3'-UTRs of AhRbcS1 mRNA from the C4 dicot amaranth were linked to a gusA reporter gene. These were constitutively transcribed from a cauliflower mosaic virus promoter and assayed for posttranscriptional expression patterns in transgenic lines of the C4 dicot Flaveria bidentis.

Mucin/poly(acrylic acid) interactions: a spectroscopic investigation of mucoadhesion.

Studies using infrared, (1)H and (13)C nuclear magnetic resonance, and X-ray photoelectron spectroscopies and differential scanning calorimetry support the hypothesis that hydrogen bonds, formed between the carboxylic acid functionality of the mucoadhesive material poly(acrylic acid) and the glycoprotein component of mucus, play a significant role in the process of mucoadhesion. There are fewer H-bonded interactions between the components than within the bulk of the pure mucoadhesive agent. The pH of the medium influences the structures of both the poly(acrylic acid) and the mucus, which, in turn, determine the nature and the extent of mucoadhesive interactions.

Opioid agonists differentially regulate mu-opioid receptors and trafficking proteins in vivo.

Chronic opioid agonist treatment produces tolerance and in some cases opioid receptor internalization and down-regulation. Both morphine and etorphine induce tolerance; however, only etorphine produces mu-opioid receptor (muOR) down-regulation. In vitro studies implicate dynamin-2 (DYN-2) and G-protein receptor kinase-2 (GRK-2) in these processes.

Antagonist-induced micro-opioid receptor up-regulation decreases G-protein receptor kinase-2 and dynamin-2 abundance in mouse spinal cord.

Chronic treatment with opioid receptor antagonists has been shown to increase the density of micro-, delta- and kappa-opioid receptors in cell culture and in the intact animal. Although opioid receptor antagonist-induced up-regulation is a robust phenomenon, the mechanisms responsible for the increase in receptor density remain unclear. In the present study, changes in a kinase and a GTPase that have been implicated in G-protein-coupled receptor regulation were examined following opioid receptor antagonist treatment.