To investigate the impact of patient and public involvement (PPI) on rates of enrolment and retention in clinical trials and explore how this varies with the context and nature of PPI.
To determine whether use of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes.
A novel rhodium-catalyzed dearomatization of O-substituted pyridines to access N-substituted 2-pyridones has been developed. Computational study suggested a mechanism involving the formation of a pyridinium ylide followed by an unprecedented 1,4-acyl migratory rearrangement from O-to-C. Furthermore, using chiral dirhodium complexes as the catalyst, the asymmetric transformation has been achieved with excellent enantioselective control. DFT calculations indicate the chirality has been established from axial chirality to central stereogenic centre. The stronger π-π interaction and CH-π interaction accounts for the high enantioselectivity.
Bupropion is antidepressant and a smoking cessation aid medication related to dopaminergic activity. We report for the first time a case of an older adult with a known tic disorder, which was in remission but exacerbated during treatment with bupropion. It has been reported that other dopaminergic compounds such as methylphenidate can exacerbate tic disorder. Clinicians should be aware of this potential adverse effect when prescribing bupropion to adults with tic and other motor disorders.
To assess the temporal change in test use in UK primary care and to identify tests with the greatest increase in use.
To determine whether medical errors, family experience, and communication processes improved after implementation of an intervention to standardize the structure of healthcare provider-family communication on family centered rounds.
To evaluate the diagnostic accuracy of high-risk human papillomavirus (hrHPV) assays on self samples and the efficacy of self sampling strategies to reach underscreened women.
To compare age standardised death rates for respiratory disease mortality between the United Kingdom and other countries with similar health system performance.
Hippocampal ripple oscillations likely support reactivation of memory traces that manifest themselves as temporally organized spiking of sparse neuronal ensembles. However, the network mechanisms concurring to achieve this function are largely unknown. We designed a multi-compartmental model of the CA3-CA1 subfields to generate biophysically realistic ripple dynamics from the cellular level to local field potentials. Simulations broadly parallel in vivo observations and support that ripples emerge from CA1 pyramidal spiking paced by recurrent inhibition. In addition to ripple oscillations, key coordination mechanisms involve concomitant aspects of network activity. Recurrent synaptic interactions in CA1 exhibit slow-gamma band coherence with CA3 input, thus offering a way to coordinate CA1 activities with CA3 inducers. Moreover, CA1 feedback inhibition controls the content of spontaneous replay during CA1 ripples, forming new mnemonic representations through plasticity. These insights are consistent with slow-gamma interactions and interneuronal circuit plasticity observed in vivo, suggesting a multifaceted ripple-related replay phenomenon.
Dynamic changes in astrocyte free Ca2+ regulate synaptic signaling and local blood flow. Although astrocytes are poised to integrate signals from synapses and the vasculature to perform their functional roles, it remains unclear what dictates astrocyte responses during neurovascular coupling under realistic conditions. We examined peri-arteriole and peri-capillary astrocytes in the barrel cortex of active mice in response to sensory stimulation or volitional behaviors. We observed an AMPA and NMDA receptor-dependent elevation in astrocyte endfoot Ca2+ that followed functional hyperemia onset. This delayed astrocyte Ca2+ signal was dependent on the animal’s action at the time of measurement as well as a neurovascular pathway that linked to endothelial-derived nitric oxide. A similar elevation in endfoot Ca2+ was evoked using vascular chemogenetics or optogenetics, and opto-stimulated dilation recruited the same nitric oxide pathway as functional hyperemia. These data show that behavioral state and microvasculature influence astrocyte Ca2+ in active mice. VIDEO ABSTRACT.