Modulation of excitatory synaptic transmission in the rat spinal dorsal horn

Modulation of excitatory amino acid (EAA)-mediated synaptic transmission in the rat spinal dorsal horn by the cyclic adenosine 3[superscript]\u27,5[superscript]\u27-monophosphate (cyclic AMP)-dependent second-messenger system and by the activation of metabotropic glutamate receptors has been investigated by using sharp-electrode voltage recording in the transverse spinal cord slice preparation and whole-cell voltage-clamp recording from acutely dissociated dorsal horn neurons;The elevation of intracellular concentration of cyclic AMP by membrane permeable analog, 8-Br cyclic AMP, and application of phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), depolarize rat spinal dorsal horn neurons. In addition they enhance presumed monosynaptic excitatory postsynaptic potentials evoked in the substantia gelatinosa neurons by orthodromic stimulation of a lumbar dorsal root and the responses of dorsal horn neurons to specific agonists of glutamate receptor subtypes (N-methyl-D-aspartic acid (NMDA), [alpha]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid (QA) and kainic acid (KA)). Specific protein kinase inhibitor (PKI[subscript]5-24), that binds with high affinity to the active catalytic subunit of cyclic AMP-dependent protein kinase, prevented the 8-Br cyclic AMP-induced depolarization of the resting membrane potential and the potentiation of NMDA responses of dorsal horn neurons. Direct intracellular administration of cAMP or catalytic subunit of protein kinase A resulted in enhanced responsiveness of DH neurons to NMDA, whereas heat-inactivated cPKA did not modulate NMDA-induced currents;In freshly isolated DH neurons (±)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) and its active enantiomere 1S,3R-ACPD, the agonist of metabotropic glutamate receptor increased the whole-cell current responses to Glu, AMPA, and NMDA. The responses to KA were little affected. The enhancing effect was long-lasting (up to 75 min after the onset of application of ACPD) and was in a proportion (42%) of DH neurons preceded by a transient depression. 2-Amino-3-phosphono-propionic acid (L-AP[subscript]3), a putative antagonist of metabotropic glutamate receptor, exerted little effect on responses of DH neurons to AMPA itself, but reduced or prevented the enhancing effect of trans-ACPD;These results suggest that in the rat spinal dorsal horn the activation of the adenylate cyclase-cyclic AMP-dependent protein kinase system and metabotropic glutamate receptor may be involved in the regulation of the sensitivity of postsynaptic excitatory amino acid (NMDA, AMPA, KA) receptors and primary afferent neurotransmission, including nociception

Promoting Renewable Energy Generation in the United States: The Debate over Renewable Portfolio Standards

Incentivizing renewable energy growth in the 21st century is, and will continue to be, a highly debated topic. As of late, legislative initiatives have prompted the enactment of various renewable portfolio standards aimed at stimulating renewable energy growth. Using data regarding each state’s energy production, this paper finds that there is no significant change in renewable energy output following the initiation of a renewable portfolio standard. We conclude that renewable energy growth is virtually unaffected by renewable portfolio standards and as such, we agree with much of the literature implying other means are necessary in order to adequately shift the energy portfolio of each of the United States

Therapeutic interventions for people living with dementia: A review of informal carer training for the behavioural and psychological symptoms of dementia (BPSD) and an evaluation of virtual cognitive stimulation therapy (vCST)

Aims: Cognitive Stimulation Therapy (CST) is an evidence-based group intervention for people living with dementia, which has proven benefits for cognition and quality of life when delivered face-to-face. Online delivered, ‘virtual’ CST (vCST) has never been empirically examined before now, however a clear need for an online protocol and evidence of its efficacy has emerged during the COVID-19 pandemic. As a preliminary response to this urgent need, this study aimed to assess vCST acceptability, and potential cognitive benefits. Method: This research consisted of a controlled, proof-of-concept study, mixed in design by incorporating pre-post quantitative cognitive measures and qualitative interview data. Descriptive and inferential statistics were used to tentatively explore initial effects and trends. A thematic analysis was conducted to explore the acceptability of vCST and facilitators and barriers of access. Results: Twenty two participants were recruited; 12 formed a treatment group; 10 formed a treatment-as-usual (TAU) control group. Two participants dropped-out due to worsening health. 11 participants were interviewed for feedback about their experiences. Quantitative analyses found no significant differences in change scores between groups. Some descriptive trends indicated a stabilisation of cognition within the vCST group. Thematic analysis identified 13 sub-themes across four main themes; ‘being online’; ‘connections with others in vCST’; ‘feelings about vCST’; and ‘transfer of CST processes and outcomes to a virtual modality’. Conclusions: This research did not find statistically significant benefits of vCST on cognitive measures. Attrition rates and qualitative feedback demonstrated that vCST is a feasible and acceptable intervention for some people living with dementia. However, a majority still prefer face-to-face groups, despite acknowledging the potential benefits of a vCST provision beyond the COVID-19 pandemic. Multiple factors are considered in interpreting these results, and further research is recommended to determine the efficacy of vCST

Late Thrombosis of Sirolimus-Eluting Stent: A Multifactorial Problem

We report a case of a young patient in whom a sirolimus-eluting stent was implanted on the culprit left anterior descending coronary artery at primary percutaneous coronary intervention (PCI) for acute myocardial infarction. Nine months later she suffered from a reinfarction due to the late stent thrombosis despite a continuous antiplatelet therapy with aspirin and clopidogrel. A cluster of factors that might have contributed to the development of the stent thrombosis were identified: suboptimal PCI technique, complete stent fracture, and clopidogrel resistance. The obstructed stent was successfully reopened by repeat PCI, while the clopidogrel maintenance dosage was doubled to 150 mg daily for the following year. The further long-term clinical course was uneventful

Ascites in Advanced Ovarian Cancer

The presence of ascites is one of the general ovarian cancer (OC) symptoms detected at initial diagnosis and can be present at an early stage but is most often seen in advanced disease. In newly diagnosed OC patients, ascites is treated by the standard treatment for the underlying disease. However, once the chemoresistant and recurrent features of the disease develop, management of a large volume of ascites can be a major problem. By increasing abdominal pressure, ascites can cause severe symptoms; thus, palliation of symptomatic patients is the main goal. The elimination of fluid accumulation in OC patients with these symptoms will certainly improve their quality of life and may even prolong survival. Unfortunately, no standard treatment for OC-associated ascites exists. There are several traditional therapies for ascites, with limited effectiveness and significant adverse effects. Catumaxomab is the only medicine approved for intraperitoneal treatment of malignant ascites in patients with EpCAM-positive carcinomas. Advances in our understanding of malignant ascites aetiology and more effective treatment strategies for ascites and OC will help reduce the symptoms associated with ascites