The application of maximal heart rate predictive equations in hypoxic conditions.

Purpose: Peak heart rate (HRpeak) is a common tool used in exercise prescription for groups in which maximal exercise intensity is contraindicated; however, the application of this method in normobaric hypoxia is unknown. Therefore, this study investigated the response of HRpeak and the application of predictive HRpeak equations to prescribe exercise intensity in acute normobaric hypoxia. Results were used to examine whether age-derived HRpeak predictive equations are valid in hypoxic conditions.

Addition of heart score to high-sensitivity troponin T versus conventional troponin T in risk stratification of patients with chest pain at the coronary emergency rooms.

Patients with chest pain have a large impact on available resources in coronary emergency rooms (CER). Clinical judgement, ECG, risk scores and biomarkers guide in risk stratification. We investigated if high-sensitivity troponin T (HsT) and the HEART Score could contribute to risk stratification at the CER.

Responses of the spleen to intraamniotic lipopolysaccharide exposure in fetal sheep.

Background: Intrauterine inflammation activates the fetal immune system and can result in organ injury and postnatal complications in preterm infants. As the spleen is an important site for peripheral immune activation, we asked how the fetal spleen would respond to intrauterine inflammation over time. We hypothesized that intraamniotic lipopolysaccharide (IA LPS) exposure induces acute and persistent changes in the splenic cytokine profile and T-cell composition that may contribute to the sustained fetal inflammatory response after chorioamnionitis.

Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity.

Purpose: Submicroscopic deletions of chromosome band 2p25.3 are associated with intellectual disability and/or central obesity. Although MYT1L is believed to be a critical gene responsible for intellectual disability, so far no unequivocal data have confirmed this hypothesis.

A new efficient algorithm for inferring explicit hybridization networks following the Neighbor-Joining principle.

Several algorithms and software have been developed for inferring phylogenetic trees. However, there exist some biological phenomena such as hybridization, recombination, or horizontal gene transfer which cannot be represented by a tree topology. We need to use phylogenetic networks to adequately represent these important evolutionary mechanisms.

Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.

Background: Intellectual disability (ID) is characterised by an extreme genetic heterogeneity. Several hundred genes have been associated to monogenic forms of ID, considerably complicating molecular diagnostics. Trio-exome sequencing was recently proposed as a diagnostic approach, yet remains costly for a general implementation.

N-tetradecylcarbamyl lipopeptides as novel agonists for Toll-like receptor 2.

New analogues (UPam) of triacylated lipopeptide Pam3CysSK4, a popular agonist of Toll-like receptor 2 (TLR2), were designed making use of the cocrystal structure of a TLR2 heterodimer (with TLR1) with Pam3CysSK4. Twenty-two UPam derivatives that feature an N-tetradecylcarbamyl chain to mimic the native N-palmitoyl moiety and various small amino acids residues at the penultimate N-terminal position were prepared via solid-phase synthesis. In vitro evaluation of immunostimulatory properties revealed new potent TLR2 ligands.

Flatworm models in pharmacological research: the importance of compound stability testing.

Flatworms possess adult pluripotent stem cells, which make them extraordinary experimental model organisms to assess in vivo the undesirable effects of substances on stem cells. Currently, quality practices, implying evaluation of the stability of the test compound under the proposed experimental conditions, are uncommon in this research field. Nevertheless, performing a stability study during the rational design of in vivo assay protocols will result in more reliable assay results.

Design, automated synthesis and immunological evaluation of NOD2-ligand-antigen conjugates.

The covalent attachment of an innate immune system stimulating agent to an antigen can provide active vaccine modalities capable of eliciting a potent immune response against the incorporated antigen. Here we describe the design, automated synthesis and immunological evaluation of a set of four muramyl dipeptide-peptide antigen conjugates. Muramyl dipeptide (MDP) represents a well-known ligand for the intracellular NOD2 receptor and our study shows that covalently linking an MDP-moiety to an antigenic peptide can lead to a construct that is capable of stimulating the NOD2 receptor if the ligand is attached at the anomeric center of the muramic acid.

Toxicity profiles and solvent-toxicant interference in the planarian Schmidtea mediterranea after dimethylsulfoxide (DMSO) exposure.

To investigate hydrophobic test compounds in toxicological studies, solvents like dimethylsulfoxide (DMSO) are inevitable. However, using these solvents, the interpretation of test compound-induced responses can be biased. DMSO concentration guidelines are available, but are mostly based on acute exposures involving one specific toxicity endpoint.

A decision aid regarding treatment options for patients with an asymptomatic abdominal aortic aneurysm: a randomised clinical trial.

Objective: Abdominal aortic aneurysm patients tend to be informed inconsistently and incompletely about their disorder and the treatment options open to them. The objective of this trial was to evaluate whether these patients are better informed and experience less decisional conflict regarding their treatment options after viewing a decision aid.

Design: A six-centre, randomised clinical trial comparing a decision aid plus regular information versus regular information from the surgeon.

Acute postexercise effects of concentric and eccentric exercise on glucose tolerance.

Impaired glucose tolerance was shown to be present 48 hr following muscle-damaging eccentric exercise. We examined the acute effect of concentric and muscle-damaging eccentric exercise, matched for intensity, on the responses to a 2-hr 75-g oral glucose tolerance test (OGTT). Ten men (27 ± 9 years, 178 ± 7 cm, 75 ± 11 kg, VO₂max: 52.

A homozygous missense mutation in the ciliary gene TTC21B causes familial FSGS.

Several genes, mainly involved in podocyte cytoskeleton regulation, have been implicated in familial forms of primary FSGS. We identified a homozygous missense mutation (p.P209L) in the TTC21B gene in seven families with FSGS.

Preimplantation genetic diagnosis for cystic fibrosis: the Montpellier center's 10-year experience.

This study provides an overview of 10 years of experience of preimplantation genetic diagnosis (PGD) for cystic fibrosis (CF) in our center. Owing to the high allelic heterogeneity of CF transmembrane conductance regulator (CFTR) mutations in south of France, we have set up a powerful universal test based on haplotyping eight short tandem repeats (STR) markers together with the major mutation p.Phe508del.

Effect of acute normobaric hypoxia on the ventilatory threshold.

Purpose: This study investigated the response of the ventilatory threshold (VT) to acute normobaric hypoxia and compared the agreement between software-based algorithms which use automatic detection to identify the VT. Results were used to examine whether the VT can be used as a physiological parameter to prescribe and monitor exercise intensity in hypoxic exercise training programs.

Methods: Fourteen untrained individuals (7 women, 7 men; age 22 ± 2 years, [Formula: see text]O2peak 46 ± 7 mL kg(-1) min(-1)) completed five identical graded exercise tests (randomized order) on a cycle ergometer to measure VT at sea-level (SL) and in response to four normobaric hypoxic conditions (FIO2: 0.

Chorioamnionitis-induced fetal gut injury is mediated by direct gut exposure of inflammatory mediators or by lung inflammation.

Intra-amniotic exposure to proinflammatory agonists causes chorioamnionitis and fetal gut inflammation. Fetal gut inflammation is associated with mucosal injury and impaired gut development. We tested whether this detrimental inflammatory response of the fetal gut results from a direct local (gut derived) or an indirect inflammatory response mediated by the chorioamnion/skin or lung, since these organs are also in direct contact with the amniotic fluid.

Aging, functional capacity and eccentric exercise training.

Aging is a multi-factorial process that ultimately induces a decline in our physiological functioning, causing a decreased health-span, quality of life and independence for older adults. Exercise participation is seen as a way to reduce the impact of aging through maintenance of physiological parameters. Eccentric exercise is a model that can be employed with older adults, due to the muscle's ability to combine high muscle force production with a low energy cost.

CEP57 mutation in a girl with mosaic variegated aneuploidy syndrome.

Mosaic variegated aneuploidy (MVA) is a rare autosomal recessive disorder characterized by constitutional aneuploidies. Mutations in BUB1B and CEP57 genes, which are involved in mitotic spindle and microtubule stabilization, respectively, are responsible for a subset of patients with MVA. To date, CEP57 mutations have been reported only in four probands.

Altered canonical Wingless-Int signaling in the ovine fetal lung after exposure to intra-amniotic lipopolysaccharide and antenatal betamethasone.

Background: Antenatal inflammation and maternal corticosteroids induce fetal lung maturation but interfere with late lung development. Canonical Wingless-Int (Wnt) signaling directs lung development and repair. We showed that intra-amniotic (IA) lipopolysaccharide (LPS) exposure disrupted developmental signaling pathways in the preterm lamb lungs.

Do knowledge brokers facilitate implementation of the stroke guideline in clinical practice?

Background: The implementation of clinical practice guidelines in rehabilitation practice is often troublesome and incomplete. An intervention to enhance the implementation of guidelines is the knowledge transfer program built around the activities of a knowledge broker (KB).This study investigates the use of KBs to implement guideline recommendations for intensive therapy and physical activity for patients post-stroke in 22 stroke units in hospitals and rehabilitation centers in The Netherlands.

Neuromuscular impairment following backpack load carriage.

Load Carriage using backpacks is an occupational task and can be a recreational pursuit. The aim of this study was to investigate the mechanisms responsible for changes in neuromuscular function of the m. quadriceps femoris following load carriage.

Adipose dipeptidyl peptidase-4 and obesity: correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro.

Objective: To study expression of the recently identified adipokine dipeptidyl peptidase-4 (DPP4) in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of patients with various BMIs and insulin sensitivities, as well as to assess circulating DPP4 in relation to obesity and insulin sensitivity.

Research Design And Methods: DPP4 expression was measured in SAT and VAT from 196 subjects with a wide range of BMIs and insulin sensitivities. DPP4 release was measured ex vivo in paired biopsies from SAT and VAT as well as in vivo from SAT of lean and obese patients.

Tacrolimus does not affect early wound healing in a rodent model of bowel anastomoses and abdominal wall closure.

Background: Use of immunosuppressant drugs has been associated with complications in wound healing. The calcineurin inhibitor tacrolimus is thought to have a relatively low complication rate, but preclinical research has yielded contradictory data, prompting the current comprehensive study.

Methods: Three groups of 33 male Wistar rats received a daily subcutaneous dose of 0,5, 2 or 5 mg/kg tacrolimus.

VEGF in the crosstalk between human adipocytes and smooth muscle cells: depot-specific release from visceral and perivascular adipose tissue.

Adipose tissue secrets adipokines and fatty acids, which may contribute to obesity-associated vascular dysfunction and cardiovascular risk. This study investigated which factors are responsible for the synergistic effect of adipokine and oleic acid- (OA-) induced proliferation of human vascular smooth muscle cells (VSMC). Adipocyte-conditioned medium (CM) from human adipocytes induces proliferation of VSMC in correlation to its vascular endothelial growth factor (VEGF) content.