Anticoagulation in patients with atrial fibrillation,thrombocytopenia and hematological malignancy

Journal of Thrombosis and Thrombolysis - Managing anticoagulation in hematological malignancy patients with atrial fibrillation and thrombocytopenia is a clinical challenge with limited data. We...     

Metaphor Comprehension in Individuals with Autism Spectrum Disorder: Core Language Skills Matter

Journal of Autism and Developmental Disorders - Poor metaphor comprehension was considered a hallmark of autism spectrum disorder (ASD), but recent research has questioned the extent and the...     

Access to sexual and reproductive health care: adolescents and young people.

Obstetricians and gynecologists at the FIGO pre-congress workshop on adolescents deliberated on their role as clinicians, educators and advocates in upholding young peoples' sexual and reproductive health rights. Comprehensive services to adolescents should include emergency contraception, safe abortion and also provide care for survivors of sexual violence. Key to successful access to youth friendly services consist of providers' attitudes and addressing consent, confidentiality, evolving capacities of young people and youth participation.     

2-Amino-3,4-dihydroquinazolines as inhibitors of BACE-1 (beta-site APP cleaving enzyme): Use of structure based design to convert a micromolar hit into a nanomolar lead

A new aspartic protease inhibitory chemotype bearing a 2-amino-3,4-dihydroquinazoline ring was identified by high-throughput screening for the inhibition of BACE-1. X-ray crystallography revealed that the exocyclic amino group participated in a hydrogen bonding array with the two catalytic aspartic acids of BACE-1 (Asp(32), Asp(228)). BACE-1 inhibitory potency was increased (0.9 microM to 11 nM K(i)) by substitution into the unoccupied S(1)' pocket.     

Astrocytes regulate GluR2 expression in motor neurons and their vulnerability to excitotoxicity

Influx of Ca(2+) ions through alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors contributes to neuronal damage in stroke, epilepsy, and neurodegenerative disorders such as ALS. The Ca(2+) permeability of AMPA receptors is largely determined by the glutamate receptor 2 (GluR2) subunit, receptors lacking GluR2 being permeable to Ca(2+) ions. We identified a difference in GluR2 expression in motor neurons from two rat strains, resulting in a difference in vulnerability to AMPA receptor-mediated excitotoxicity both in vitro and in vivo. Astrocytes from the ventral spinal cord were found to mediate this difference in GluR2 expression in motor neurons. The presence of ALS-causing mutant superoxide dismutase 1 in astrocytes abolished their GluR2-regulating capacity and thus affected motor neuron vulnerability to AMPA receptor-mediated excitotoxicity. These results reveal a mechanism through which astrocytes influence neuronal functioning in health and disease.