Non-Surgical Respiratory Management in Relation to Feeding and Growth in Patients with Robin Sequence; a Prospective Longitudinal Study.

Objective: To reflect upon our non-surgical respiratory management by evaluating clinical outcomes regarding airway, feeding, and growth during the first year of life in patients with Robin Sequence.

Design: Prospective study.

Setting: Sophia Children's Hospital, Rotterdam, the Netherlands.

A comparison of two Fendrix hepatitis B vaccination schedules in patients with inflammatory bowel disease.

Systemic immunosuppressive therapy (IS) renders patients with inflammatory bowel disease (IBD) vulnerable to fulminant hepatitis B virus (HBV) infection. Seroprotection against HBV through a full vaccination scheme is preferably obtained before IS is initiated, but often conflicts with the clinical need to initiate therapy rapidly. Consequently, the vast majority of patients will use IS during booster vaccinations.

Comparison of the Anti-Tumour Activity of the Somatostatin Receptor (SST) Antagonist [Lu]Lu-Satoreotide Tetraxetan and the Agonist [Lu]Lu-DOTA-TATE in Mice Bearing AR42J SST-Positive Tumours.

Limited experiments have compared the treatment effects of repetitive cycles of radiolabelled somatostatin (SST) analogues. In vitro and in vivo experiments were conducted in an AR42J cancer cell model, comparing the antagonist [Lu]Lu-satoreotide tetraxetan with the agonist [Lu]Lu-DOTA-TATE in terms of their binding properties, biodistribution, anti-tumour activity and toxicity. Histopathological and immunohistochemical examinations were performed at different timepoints.

Distinct In Vitro Binding Profile of the Somatostatin Receptor Subtype 2 Antagonist [Lu]Lu-OPS201 Compared to the Agonist [Lu]Lu-DOTA-TATE.

Treatment of neuroendocrine tumours with the radiolabelled somatostatin receptor subtype 2 (SST) peptide agonist [Lu]Lu-DOTA-TATE is effective and well-established. Recent studies suggest improved therapeutic efficacy using the SST peptide antagonist [Lu]Lu-OPS201. However, little is known about the cellular mechanisms that lead to the observed differences.

Feeding and swallowing outcomes following mandibular distraction osteogenesis: an analysis of 22 non-isolated paediatric cases.

Patients with mandibular hypoplasia and upper airway obstruction are at an increased risk of feeding and swallowing difficulties. Little has been described regarding these outcomes following mandibular distraction. The aim of this study was to evaluate the effect of mandibular distraction on feeding and swallowing function.

Mandibular distraction to correct severe non-isolated mandibular hypoplasia: The role of drug-induced sleep endoscopy (DISE) in decision making.

Objectives: In patients with mandibular hypoplasia, mandibular distraction osteogenesis (MDO) aims to relieve tongue-based airway obstruction. Drug-induced sleep endoscopy (DISE) provides a dynamic assessment of the upper airway and visualizes anatomical site and cause of airway obstruction. The aim of this study was to evaluate the effect of MDO on tongue-based airway obstruction found by DISE within a non-isolated patient population with severe upper airway obstruction (UAO).

Functional outcomes in patients with facial dysostosis and severe upper airway obstruction.

An increased risk of upper airway obstruction (UAO) is seen in up to 95% of patients with facial dysostosis. Secondary to respiratory problems are feeding difficulties and increased nutritional requirements. Little has been described regarding these outcomes in this patient population.

Effect of weight change on progression of knee OA structural features assessed by MRI in overweight and obese women.

Objective: To evaluate the effects of weight change on progression of knee osteoarthritis (OA) structural features by magnetic resonance imaging (MRI) in overweight and obese women without clinical knee OA.

Design: 347 participants from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study were classified with latent class growth analysis into a subgroup with steady weight (n = 260; +0.1 ± 4.

Baseline meniscal extrusion associated with incident knee osteoarthritis after 30 months in overweight and obese women.

Objective: To investigate the association between baseline meniscal extrusion and the incidence of knee osteoarthritis (KOA) after 30 months in a high-risk population of overweight and obese women, free of clinical and radiological KOA at baseline.

Methods: 407 middle-aged overweight women (body mass index - BMI ≥ 27 kg/m) were evaluated at baseline and after 30 months of follow-up. Meniscal extrusion was defined as grade ≥2 on MRI according to MRI Osteoarthritis Knee Score (MOAKS).

Tasquinimod modulates tumor-infiltrating myeloid cells and improves the antitumor immune response to PD-L1 blockade in bladder cancer.

The infiltration of myeloid cells helps tumors to overcome immune surveillance and imparts resistance to cancer immunotherapy. Thus, strategies to modulate the effects of these immune cells may offer a potential therapeutic benefit. We report here that tasquinimod, a novel immunotherapy which targets S100A9 signaling, reduces the immunosuppressive properties of myeloid cells in preclinical models of bladder cancer (BCa).

Reducing progression of knee OA features assessed by MRI in overweight and obese women: secondary outcomes of a preventive RCT.

Objective: To evaluate the preventive effects of a randomized controlled trial on progression of Magnetic Resonance Imaging (MRI) features of knee osteoarthritis (OA) in overweight and obese women.

Design: In a 2 × 2 factorial design, 2.5 years effects of a diet and exercise program and of glucosamine sulphate (double-blind, placebo-controlled) were evaluated in 407 middle-aged women with body mass index (BMI) ≥ 27 kg/m(2) without clinical signs of knee OA at baseline (ISRCTN 42823086).

Tasquinimod triggers an early change in the polarization of tumor associated macrophages in the tumor microenvironment.

Background: Tasquinimod (a quinoline-3-carboxyamide) is a small molecule immunotherapy with demonstrated effects on the tumor microenvironment (TME) involving immunomodulation, anti-angiogenesis and inhibition of metastasis. A target molecule of tasquinimod is the inflammatory protein S100A9 which has been shown to affect the accumulation and function of suppressive myeloid cell subsets in tumors. Given the major impact of myeloid cells to the tumor microenvironment, manipulation of this cell compartment is a desirable goal in cancer therapeutics.

Tasquinimod inhibits prostate cancer growth in bone through alterations in the bone microenvironment.

Background: Tasquinimod (ABR-215050) is an orally active quinoline-3-carboxamide analog that inhibits occurrence of experimental metastasis and delays disease progression of castration resistant prostate cancer in humans. Its mechanism of action is not fully elucidated, but previous studies show immunomodulatory and anti-angiogenic effects. The aim of the present study was to investigate the tumor inhibiting effect of tasquinimod in bone of castrated mice as well as to elucidate its working mechanism related to bone microenvironment.

Novel pharmacological MC4R agonists can efficiently activate mutated MC4R from obese patient with impaired endogenous agonist response.

Human melanocortin 4 receptor (hMC4R) mutations with in vitro functional effects are responsible for 0.5-2.5% of severe obesity.

Analysis of the therapeutic functions of novel melanocortin receptor agonists in MC3R- and MC4R-deficient C57BL/6J mice.

Melanocortin receptor agonists act in the brain to regulate food intake and body weight and, independently of these actions, affect insulin sensitivity. These experiments investigated the function of novel non-selective melanocortin receptor agonists (BIM-22493, BIM-22511) that cross the blood-brain barrier when administered peripherally. Treatment of diet induced obese C57BL/6J (B6) mice with melanocortin agonists administered peripherally improved obesity, hyperinsulinemia (approximately 50%) and fatty liver disease.

Identification of a novel series of benzimidazoles as potent and selective antagonists of the human melanocortin-4 receptor.

A novel series of benzimidazoles was identified and optimized, leading to the discovery of potent and selective antagonists of the human melanocortin-4 receptor. In addition, compound 5i was shown to cross the blood-brain barrier after intravenous dosing in rats.

3-Thio-1,2,4-triazoles, novel somatostatin sst2/sst5 agonists.

Novel 3-thio-1,2,4-triazoles have been obtained via a solution-phase parallel synthesis strategy, affording potent non-peptidic human somatostatin receptor subtypes 2 and 5 agonists.

Identification of potent non-peptide somatostatin antagonists with sst(3) selectivity.

Using a solution-phase parallel synthesis strategy, a series of non-peptide somatostatin analogues were prepared, and their binding affinities to the five human somatostatin receptor subtypes (sst(1-5)) were determined. Imidazolyl derivatives 2 were found to bind with moderate affinity but with high selectivity to the sst(3) receptor subtype. Further modifications of these structures led to a more potent class of ligands, the tetrahydro-beta-carboline derivatives 4.

Decrease in endothelin-1 renal receptors during the 1st month of life in the rat.

Endothelin-1 (Et1), like angiotensin II, is implicated in postnatal maturation and development. The present study was designed to identify Et1 receptors and subtype Et1 receptors present in rat kidney between 1 and 30 days of postnatal life. On day 1, high-affinity and high-density Et1 binding sites were identified in rat kidney.

Endothelin receptor subtypes A and B are up-regulated in an experimental model of acute renal failure.

The two endothelin (ET) receptor subtypes (ETA and ETB) have been characterized in rat kidney from normal rats and rats with acute renal failure induced by hypertonic glycerol administration. In control rats, the total number of ET receptors in kidney cortex and medulla was 155 and 386 fmol/mg of protein, respectively. The ratio of ETA to ETB receptors was 54:46 in renal cortex and 35:65 in renal medulla.

Endothelin receptor regulation by endothelin synthesis in vascular smooth muscle cells: effects of dexamethasone and phosphoramidon.

One of the major biological effects of the endothelium-derived peptide endothelin-1 (ET-1) is its receptor-mediated constrictive action on vascular smooth muscle. In this study, we have examined the effects on the ET-1 pathway of 18 h exposure at 37 degrees C of cultured rat aortic smooth muscle cells to dexamethasone (DEX) and phosphoramidon. ET-1 synthesis was evaluated by radioimmunoassay, ET-1 binding characteristics were determined with [125I]iodo-ET-1, and ET-1-induced intracellular calcium mobilization was measured using fura-2-loaded cells.

Upregulation of renal endothelin receptors in glycerol-induced acute renal failure in the rat.

Acute renal failure was induced in rat with a hypertonic glycerol solution and endothelin-1 (ET-1) binding was measured in kidney membrane preparations. In control animals, [125I]-ET-1 bound to specific recognition sites in kidney cortex (Bmax = 134 +/- 11 fmol/mg protein) and medulla (Bmax = 300 +/- 9 fmol/mg protein) with an apparent dissociation constant (Kd) of 0.16 +/- 0.